Hand Book of

PEDIATRIC
NEPHROLOGY
3rd Edition

Ranjit Roy
Tahmina Jesmin
Abdullah Al Mamun
Nadira Sultana
 Hand Book of
PEDIATRIC
NEPHROLOGY
3rd Edition

Ranjit Roy
Tahmina Jesmin
Abdullah Al Mamun
Nadira Sultana
ISBN: 978-984-34-1238-6

Hand Book of
PEDIATRIC NEPHROLOGY

Published by:
Pediatric Study Group
Bangabandhu Sheikh Mujib Medical University
Dhaka, Bangladesh

Cover & Graphic Design:

Dr. Abdullah Al Mamun

© All rights reserved by the author. No part of this book shall be

reproduced, stored in retrieved or transmitted in any form or by
any means, electronic, mechanical, photocopying or otherwise
without prior permission of the author.

3rd Edition

Price: Tk. 750

US$ 10

Available At:
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Dolphin Book Aziz super market, Shahbagh, Dhaka-1000
City Books
Capital Library, Nilkhet, Dhaka- 1205

Printed by:
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Preface to First Edition
Pediatric renal diseases comprise huge hidden burden throughout the
globe specially in developing countries. Difficulties in management of
potentially treatable renal diseases in resource poor, technological background
countries and AKI related child mortality around 1990 in Bangladesh prompted
authors to write this handbook. Social structure, perception and physicians
conceptions need changes. We express respect to pioneers of pediatric
nephrology of this country. Professor M. Moazzam Hossain, Professor Md.
Munimul Haque and Professor Chowdhury Ali Kawser, Professor Mohammed
Hanif.

This manual is simplified summarized form of common pediatric renal

diseases which may be useful to both postgraduate, undergraduate
medical students and pediatricians.

Authors will humbly accept any suggestion, constructive critisim about

its content.

Professor Ranjit Ranjan Roy

Dr. Tahmina Jesmin
Dr. Md. Firoz Anjum
Preface to Third Edition
Our aim is to produce a comprehensive pediatric neohrology handbook
and inspiration is our residents.

Third edition is enriched with current global knowledge upon the subject.
We tried to include all updatings upon common disease of the pediatric
nephrology. The focus is principally patient care by all ages of pediatricians
in general and pediatric nephrologists in particular.

We wish to thank all of the contributors who worked hard to make the
hand book glorious.

We thank all of our readers from the bottom of our hearts.

We owe a major debt of gratitude to Prof. Shahana Akter Rahman,

Prof. Md. Habibur Rahman, Prof. M Moazzam Hossain.

We are grateful to our patient who has given us the opportunity to serve.

Ranjit Roy
Tahmina Jesmin
Abdullah Al Mamun
Nadira Sultana
List of Authors:
Ranjit R Roy
FCPS, MD, FRCP
Professor & Ex Chairman
Pediatric Nephrology
Course Director, Pediatrics
Bangabandhu Sheikh Mujib Medical University
Dhaka, Bangladesh

Abdullah Al Mamun
MD, MRCPS
Assistant Professor,
Pediatric Nephrology,
Bangabandhu Sheikh Mujib Medical University
Dhaka, Bangladesh

Rumana Tazia Tonny

MCPS (Ped)
Resident,
Pediatric Nephrology,
Bangabandhu Sheikh Mujib Medical University
Dhaka, Bangladesh

Tahmina Jesmin,
FCPS, MD
Assistant Professor,
Pediatric Nephrology,
Bangabandhu Sheikh Mujib Medical University
Dhaka, Bangladesh

Nadira Sultana
MRCPCH (Paces)
Resident,
Pediatric Nephrology,
Bangabandhu Sheikh Mujib Medical University
Dhaka, Bangladesh

Mst. Shanjida Sharmin,

FCPS, MD
Assistant Professor,
Pediatric Nephrology,
Bangabandhu Sheikh Mujib Medical University
Dhaka, Bangladesh
Contents
CHAPTER
1. Renal Anatomy and Physiology 01
2. Congenital Anomalies of Kidney and Urinary Tract (CAKUT) 23
3. Urine Analysis, Proteinuria and Hematuria 40
4. Urinary Tract Infection (UTI) 61
5. Acute Glomerulonephritis 79
6. Glomerulonephritis 100
7. Nephrotic Syndrome 121
8. Renal Vasculitis 176
9. Fluid, Electrolytes and Acid-base Disorder 233
10. Acute Kidney Injury 277
11. Hypertension in Children 313
12. Hemolytic Uremic Syndrome (HUS) 361
13. Chronic Kidney Disease 376
14. Obstructive Uropathy 400
15. Cystic Renal Disease / Cilliopathy 423
16. Polyuria and Polydipsia 447
17. Rickets 474
18. Urolithiasis and Nephrolithiasis 490
19. Voiding Disorder 518
20. Renal Imaging 552
21. Critical Care Nephrology 570
22. Renal Procedure 603
23. Renal Replacement Therapy 629
24. Appendix 656
Index 676
 Renal Anatomy and
Physiology 01Chapter

Introduction
 The urinary system, also known as the renal system.
 It refers to the structures that produce and conduct urine to the point
of excretion.

Organs of urinary system

 Kidney
 Ureter
 Urinary bladder
 Urethra

Kidney
 Bean shape structure
 Number- two, one on left and one on the right
 Functional unit of the kidney is nephron
 Nephrons are tightly packed to form parenchyma
 Urine is formed by nephrons

Kidney size in children

 1-5 years: 7.3 cm
 5-10 years: 8.5cm
 10-15 years: 10 cm
 Above 15 years: similar to adult

Protection of kidney:
From within outwards:
 Renal capsule- fibrous sac (true capsule)
 Perinephric fat (adipose capsule)
 Renal fascia (false capsule)- attaches to the abdominal wall
 Paranephric fat (adipose tissue capsule)
# Kidney moves 1.5 to 2.5 cm with respiration as it is a subdiaphragmatic organ
 Kidney
 Gross anatomy-
 Renal parenchyma
 Renal sinus

Cross section of kidney

Renal parenchyma
Consist two portions:
1. Cortex-
Outer in position and granular in appearance
It consist of columns (column of Bertini) and arches
Pale in color
Contains roughly 1.25 million nephrons
Thickness-1 cm(adult), average 7-10mm(children)
Cover the base of the pyramids

2. Medulla-
 Inner in position
Dark in colour
Contains 8-12 renal pyramids

Proximal
tubule
Distal
Parts of a nephron tubule Collecting
tubule

Ascending
Glomerulus Descending limb of loop
limb of loop ends
begins

Collecting
duct

Descending Ascending
limb limb

Loop of handle
To bladder

Figure 1.1: Cross section of kidney nephron

Renal pyramids
 Extension-
 Base- at corticomedullary junction
 Apex- at renal pelvis
 Extensions of cortex (renal columns) divide medulla into 8-12 renal
pyramids
 Straight segment of proximal and distal tubule extend into the cortex
from corticomedullary junction
 Renal pyramids contain loop of Henle and collecting ducts
 Pyramids+ overlying cortex=lobe
 Point of pyramid=Papilla
 Each papilla contains 10-25 opening of distal ends of collecting ducts
 2-3 minor calices unite to form major calyx
 2-3 major calices unite to form renal pelvis
 Renal pelvis then unite with the ureter

Nephron
 Functional units of kidney
 Each kidney contains about 1 million or more nephrons
 Length-50 to 55 mm
 It has 2 main parts-
 Renal corpuscle
 Renal tubule

Renal corpuscle
 Composed of-
 Glomerulous
 Bowman’s capsule
 It is beginning of the nephron

Glomerulous
 Glomerulous contains tuft of capillaries and central region of mesangium
contains cells and matrix
 It receives blood from afferent arteriols
  Glomerular blood pressure provides the driving force for water and
solutes to be filtered out of the blood and into the space made by
Bowman’s capsule
 The remainder of the blood passes into the efferent arteriole.
 The diameter of efferent arterioles is smaller than that of the afferent
arterioles, increasing hydrostatic pressure in the glomerulous

Bowman’s capsule
 The Bowman’s capsule, also called the glomerular capsule
 Surrounds the glomerulous
 It is composed of visceral inner layer formed by specialized cells
called podocytes
 Parietal outer layer composed of simple squamous epithelium
 Fluids from blood in the glomerulus are filtered through the visceral
layer of podocytes, resulting in the glomerular filtration.

Renal tubule
 Leads from the glomerular capsule
 Ends at tip of medullary pyramids
 It has 4 major regions
Proximal convoluted tubules
Loop of Henle
Distal convoluted tubules
Collecting tubules and ducts

Proximal convoluted tubule

 Arises from glomerular capsule
 Longest and most coiled region
 Lies in cortex
 Lined by simple cuboidal epithelium with brush border which help
to increase the area of absorption greatly
 Prominent microvilli for absorption

Loop of Henle
 U- shaped, distal to the PCT
 Lies in medulla
 Has 2 parts-
 Descending limb of loop of Henle
Ascending limb of loop of Henle

Ascending limb of the loop of the Henle

 It has 2 segments
 Distal/lower segment
Very thin
Lined by simple squamous epithelium
Low metabolism
Highly permeable to water
 Proximal segment
Thick

Lined by simple cuboidal epithelium with abundant mitochondria

High metabolism and active transport of salt
Enters into the cortex and continues with the DCT

Distal convoluted tubule (DCT)

 Coiled, distal to nephron loop
 Shorter than PCT
 Less coiled than PCT
 Very few microvilli
 Contacts afferent and efferent arterioles
 Contact with peritubular capillaries

Collecting duct (CD)

 DCTs of several nephrons enter into a collecting duct
 Passes into medulla
 Several CD merge into papillary duct(about 30 per papilla)
 Drain into minor calyx

Filtration Barrier
Consist of-
Capillary endothelium- pore size 70 to 100 nm
  Glomerular basement membrane- consist central dense layer, lamina
densa, lamina rara interna, lamina rara externa
 Epithelium of foot process of podocyte- podocyte has long cytoplasmic
foot process that come in contact with lamina rara externa. The
gap between individual pedicel is about 25-60 nm and bridged by
a thin slit diaphragm
The capillary wall contains negatively charged polyanionic surface glyco-
protein called podocalyxin

Juxtaglomerular apparatus
 Component-
 Mecula densa cells
 Specialized epithelial cell of DCT
 Detect the sodium concentration of fluid in tubule
 Elevated Na trigger contraction of afferent arteriole
decrease blood flow of glomerulous and filtration as well
Juxtaglomerular cells (smooth muscle cell of afferent– arteriole,
secrete renin when BP fall)
Lacis cells- also called extraglomerular mesangial cell, situated
near the mecula densa.
Function:
Systemic blood pressure and filtration rate regulation
Electrolytes homeostasis
Tubuloglomerular feedback mechanism

Types of nephron
 Types (according to length of loop of Henle and position of renal
corpuscles)-
Corticle nephrons
Juxtamedullary nephrons

Juxtamedullary Nephrons
 About 20%
 Glomerulous remains at the deeper part of cortex
 Have long loops of Henle that descend all the way to the papillary tips
  Mostly related to make the osmotic gradient to make urine concentrate
along with other function.

Renal blood supply

Ureters
 Pair of muscular tubes
 Carry urine from renal pelvis to the bladder by peristalsis
 Length- 25 cm (10”) at 13 years and above
 Parts-
Pelvis of the ureter
Abdominal part- enter into pelvis by crossing either by bifurcation
of common iliac artery or beginning of external iliac artery
Pelvic part of ureter
Enter into bladder from below and obliquely which prevents backflow
of urine
Easily obstructed or injured by renal calculi

Histology of ureter
 Mucous membrane- lined by transitional epithelium and thrown into 6
longitudinal folds when empty
 Muscular coat (smooth muscle)-
Inner longitudinal
Outer circulare
 Fibrous coat- connective tissue and elastic fibres which continuous
with renal capsule

Urinary bladder
 It is a collapsible muscular sac
 Stores and expels urine
 Full bladder spherical and extend into the abdominal cavity
 Empty bladder lies entirely within the pelvis
 Wall-
Mucosa- transitional epithelium
Muscular layer- detrusor muscle
Adventatia/ fibrous layer
  Wrinkles termed rugae
 Opening of the ureters are the common site of infection

Nerve supply

 Has both autonomic and somatic nerve supply

1. Autonomic
Sympathetic –
Efferent from spinal segment T11- L2 through the hypogastric
plexus.
They have little effect on micturition and chiefly vesomotor effect.
Function-Inhibitory to detrusor muscle(relaxation of detrusor muscle),
motor to sphincter vesicae and promoting urine retention.

Parasympathetic –
Also called nervi erigentes
Efferent from S2-S4 segment by pelvic splanchnic nerve
Function- contraction of the detrusor muscle and inhibitory to
sphincter vesicae which stimulate micturition

2. Somatic –
From S2-4 segments by pudendal nerve.
Function- innervates the external urethral sphincter and providing
voluntary control over micturition.

3. Sensory (afferent) nerves-

Present in the bladder wall, sent impulse to the brain and signal in
need to urinate when the bladder becomes full.
Pain sensation from bladder (distension or spasm of UB) carried
mainly by parasympathetic and partly by sympathetic
In spinal cord passes through lateral spinothalamic tract and awareness
of bladder by distension by posterior spinothalamic tract.
Lesion on latenal spino thalamic tract abolishes the pain sensation
but not abolish the awareness of bladder distension and desire for
micturition
4. Brain-
 Pons- facilitatory centre
 Mid brain-inhibitory centre
 Cerebral cortex
 Sensory area – awareness of fullness of bladder
 Motor cortex- sends motor drive and initiation of micturition
 Frontal cortex- voluntary control of bladder reflex.

Mechanism of micturation
Distension of bladder ( increases intravesicle presence)
 
Afferent impulses from the bladder wall reaches to the spinal cord
via the pelvic and hypogastric nerve
 
Lateral spinothalamic tract to the thalamus
 
Parasaggital part of the sensory contex of the brain
 
Awareness of fullness of bladder
 
Motor drive from the parasaggital part of the motor contex of brian
 
Descending autonomic fiber
 
Sacral parasympathetic outflow to the bladder
 
Micturition reflex
 
Voluntary inhibition of the external urethral sphincter: Via higher
cerebral cortex to Onaf’s nucleus at spinal cord
 
Micturition is initiated
Pontine micturition center: Berington nucleus of pons coordinates
and control micturition
Sympathetic (T12-L2) travelling via hypogastric nerve inhibit via
ß-adrenergic inhibitors
 Sympathetic also stimulates urethral and bladder neck muscle contraction
Higher cerebral center inhibit the sympathetic and somatic reflexes,
sphincter and bladder neck nucleus and also facilitate the contraction
of detrusor, hence a person urinates.
Voluntary control develops later and hence desire to micturition or
not can be accomplished.
5. The Bladder Stretch Reflex
6. It is a primitive spinal reflex, in which micturition is stimulated in
response to stretch of the bladder wall. It is analogous to a muscle
spinal reflex, such as the patellar reflex.
7. During toilet training in infants, this spinal reflex is overridden by the
higher centers of the brain, to give voluntary control over micturition.
8. The reflex arc:
9. Bladder fills with urine, and the bladder walls stretch. Sensory nerves
detect stretch and transmit this information to the spinal cord.
10. Interneurons within the spinal cord relay the signal to the parasympathetic
efferents (the pelvic nerve).
11. The pelvic nerve acts to contract the detrusor muscle and stimulates
micturition.
12. Although it is non-functional post childhood, the bladder stretch reflex
needs to be considered in spinal injuries (where the descending
inhibition cannot reach the bladder), and in neurodegenerative diseases
(where the brain is unable to generate inhibition).

Clinical aspects
There are two different clinical syndromes, depending on where the damage
has occurred.
 Reflex Bladder – Spinal Cord Transection Above T12
 In this case, the afferent signals from the bladder wall are unable to
reach the brain, and the patient will have no awareness of bladder
filling. There is also no descending control over the external urethral
sphincter, and it is constantly relaxed.
 There is a functioning spinal reflex, where the parasympathetic
system initiates detrusor contraction in response to bladder wall
stretch. Thus, the bladder automatically empties as it fills – known
as the reflex bladder.
 Flaccid Bladder – Spinal cord transection Below T12
  A spinal cord transection at this level will have damage the para-
sympathetic outflow to the bladder. The detrusor muscle will be paralysed,
unable to contract. The spinal reflex does not function.
 In this scenario, the bladder will fill uncontrollably, becoming abnormally
distended until overflow incontinence occurs.

Urine retention
 Besides neurogenic dysfunction of the bladder, normal bladder
emptying may be hampered by any form of obstruction, from the
level of the bladder neck downwards.
 Acute retention is a medical emergency, as the bladder has a
“normal” functional capacity with is pushed to the limit due to
accumulation of urine in an acutely obstructed reservoir. The patient
feels increasingly excruciating pain and the placement of a urinary
catheter alleviates the symptoms immediately.
 Chronic retention is a gradual procedure due to incomplete obstruction
of the urine outflow. This leads to accumulation of residual urine in the
bladder through months or even years; the bladder is therefore progressively
distended in volumes that exceed 1-1.5 liter of urine.
 Chronic retention is often accompanied by impairment of renal
function. However no pain is usually present as the bladder is
gradually stretched. Chronic retention of urine is often complicated
by infections and formation of bladder stones due to urine stasis
and accumulation of minerals in the urine.

Urethra
 Conveys urine from bladder
 Internal urethral sphincter
Retains urine in bladder
Smooth muscle and involuntary control
External urethral sphincter- provides voluntary control over voiding of urine

Urethra in female
 Three- four cm long
 Bound by connective tissue to anterior wall of vagina
 Urethral orifice exits body between vaginal orifice and clitoris
Male urethra
 Length- About 18 cm (adult), 8 cm at 3 years
 Prostatic urethra- about 2.5cm, passes from urinary bladder through
prostate
 Membranous urethra- about 0.5cm length, passes through floor of
pelvic cavity
 Bulbar urethra- contains bulbourethral gland
 Penile urethra- about 15 cm length, passes through penis
 Meatal orifice- 3mm

Embryology
 Develop from mesoderm
 Parts of mesoderm:
Paraxial mesoderm
Intermediate mesoderm- develops urogenital system
Lateral plate mesoderm
I. Somatic or parietal mesoderm layer-covering the amnion
II. Splanchnic or visceral mesoderm layer- cover intraembryonic
cavity

Intermediate mesoderm
 Urinary system and genital system develops from intermediate
mesoderm
 Both systems appear in a bulging of intermediate mesoderm called
nephrogenic cord.
 Three system develop from nephrogenic cord
I. Pronephros- appears in cervical region at 4th wks, 7-10 solid cell
groups and later disappears
II. Mesonephros- appears in thoracic and lumbar region
Mesonephric tubule- efferent duct of testis, ductus aberrans,
epoophoron, paroophoron
Mesonephric duct- from here ureteric bud develops
III. Metanephros- it appears in the lumbosacral region. It is the
permanent kidney
Development of kidney
 Nephrogenesis starts at 5th weeks of gestation and ceases by 36th
wks.
 At 36th wks, the number of nephrons is fixed for the life time.
 Differentiation of primitive kidney is stimulated by penetration of the
metanephros by ureteric bud.
 Metanephros/ permanent kidney has two parts (5 th weeks)-
I. Collecting part
II. Excretory part
 Collecting part- develops from ureteric bud. It subdivide 12 or more
generations

Derivatives of ureteric bud-

1. Ureter
2. Renal pelvis
3. Major and minor calyx
4. Intrarenal collecting system-Collecting tubules and collecting duct
(1-3millions)
 Excretory system- develops from metanephric blastema.
Derivatives of metanephric blastema-
1. Glomerulous
2. Tubules- PCT, loops of Henle, DCT

Ascend of the kidney

 Permanent kidney comes in lumber region at 9 th wks.
 Factors influencing-
Continuous lengthening of ureteric bud
Rapid sacral growth and diminution of the fetal curvature
Too small pelvic cavity
Rotation of kidney

Development of urinary bladder and urethra

 At 5th wks mesonephric ducts connects to the allantois and cloaca
 At 4th-7th wk cloaca divides into urogenital sinus anteriorly and rectum
posteriorly.
  Proximal part of urogenital sinus form the UB
 Metanepric bud opens into the trigonal area of UB.

Table 1.1 Developmental abnormalities with cause

Abnormalities Cause
Renal agenesis
Unilateral Failure of ureteric budding
Bilateral Failure of the bud to engage metanephric
mesenchyme
Renal hypoplasia Mutation in gene influencing ureteric budding
Fetal urinary tract obstruction
Environmental influnce like maternal diet
Renal dysplasia (MCDK) Abnormal differentiation of metanephros

Renal physiology
Renal functions
 Excretory function- formation of urine, excretion of metabolic waste
product
 Reabsorption of substance which is vital for body e.g glucose, amino
acids, electrolytes
 Regulation of blood pressure, body fluids, electrolytes and acid base
balance
 Maintenance of blood osmolarity
 Secretion of hormones-
Erythropoitin- peritubular interstitial cell of outer medulla and inner
cortex
Renin- Juxta glomerular apparatus / cell (JGA)

Vit-D

Prostaglandin

 Metabolic function
Vit D, Ca, Po4 metabolism
Protein, polypeptide, insulin, PTH and calcitonin metabolism
Gluconeogenesis from non glucose source e.g. glutamine during
prolong starvation
Ammonia detoxification-
 Renal
Glutamate  NH3 + secretory H+ NH4  Urine
glutaminase
Distribution of cardiac output :
 Kidney(range): 20-25%
Basic mechanism involved in kidney function
 Glomerular filtration
 Tubular reabsorption
 Tubular secretion

Table 1.2 Forces involved in glomerular filtration:

Forces mm of Hg
Favoring filtration:
 Glomerular capillary blood pressure(PGC) 60
Opposing filtration
 Fluid pressure in Bowmans space (PBS) 18
 Colloidal osmotic pressure (µGC) 32
Net filtration pressure 10

Table 1.3 Forces involved in glomerular filtration

Normal Arterial end (mmHg) Venous end (mmHg)

Hydrostatic pressure 32 32
Oncotic pressure 25 12

Glomerular filtration rate (GFR)

GFR: The volume of fluid filtered from the glomeruli into the Bowman’s
space per unit time.
Determined by-
1. Net filtration pressure
2. Permeability of the corpuscular membranes
3. Surface area available for filtration
GFR is not fixed but is subject to physiological regulation which causes
a change in net filtration pressure due to neural and hormonal input to
the afferent and efferent arterioles.
  Normal GFR- 125 ml/min/1.73m2
 Renal blood flow-1200 ml/min
 Normal plasma flow-650 ml/min
 Filtrate contains-
Crystaloids

Low molecular wt substances e.g. urea, glucose, amino acids

Almost protein free- contains only 0.03 gm/dl. Even low molecular wt
albumin (69,000 Da) can’t pass due to negatively charged protein
as well as negatively charged proteoglycan layer of capillary
No RBC

Factors affecting GFR

Factor decreasing GFR:
Constriction of afferent arteriole
Dilatation of efferent arteriole

Factor increasing GFR:

Constriction of efferent arteriole
Dilatation of afferent arteriole

Tubular reabsorption
 The movement of solute and water from the tubular lumen to interstitial
fluid and finally into blood.
 Mechanism:
Diffusion

Mediated transport

 Substance reabsorb: Na, Cl, H2O, HCO3, glucose, amino acids,

protein, PO4, Ca, Mg, urea and uric acid
 Main site- PCT, Loop of Henle

Substances completely reabsorbed

 Glucose
 Amino acids
 Proteins
 Vitamins
 Acetoacetate ions
 Tubular secretion
 The move of solute from blood into the tubular lumen
 Mechanism-
Diffusion

Transcellular mediated transport

 Substance secreted : H+, K+,NH3, organic acids and bases, urea, uric
acids, urobilinogen, cholin, creatinine, penicillin

Tubular metabolism
 The cells of the renal tubule synthesis glucose and add into the blood
 Cells also catabolise substance such as peptides which are taken
from the tubular lumen and peritubular capillaries
 Catabolism eliminates such substances from the body

Na reabsorption
 Reabsorption- 99% of filtered Na
 Site and mechanism:
 PCT- 60%, active co-transport with glucose, amino acid, low
molecular wt protein, Na-H exchanger(angiotensinogen II)
 Loop of Henle- 30%, in TALLH NaK2Cl cotransport by NKCC2
channel- frusemide sensitive
 DCT and CD- rest, in DCT thiazide sensitive NaCl cotransport
(NCCT), CT and CD aldosterone related Na reabsorption, K
and H secretion (Na-K/Na-H cation exchange)
*Cation exchange process is competitive ( k competes with H for Na)
which is enhanced by hormone aldosterone

Function of Na:
 Maintains osmolarity, tonicity and body fluid balance
 Maintains resting membrane potential
 Helps in nerve and muscle conduction
 Helps in growth and development
 Bone formation( 99% Na remain in bone)
 Glucose, amino acids reabsorption
 Aldosterone related Na reabsorption

Regulation of aldosterone secretion:

Serum K+ concentration- hyperkalamia increases the secretion
Plasma Na concentration
Renin angiotensin system
ACTH from pituitary

Renin Angiotensin Aldosterone (RAAS) system:

Angiotensin II:
 Throughout the body, angiotensin II is a potent vasoconstrictor of
arterioles
 In kidneys, angiotensin II constricts glomerular arterioles, having a
greater effect on efferent arterioles than afferent. As with most other
capillary beds in the body the constriction of afferent arterioles increase
in the arterial resistance raising systemic arterial blood pressure
and decreasing the blood flow, necessitating mechanism to keep
glomerular blood pressure up. To do this angiotensin II constricts
efferent arterioles which forces blood to build up in the glomerulus,
increasing glomerular pressure.

Renal Potassium Handling:

 Only plasma electrolyte that is both reasorbed and secreted into
the renal tubule
 Reabsorption:
65-70% in PCT
25% in TALLH by Na-K-2Cl cotransporter
Rest 10% in distal part of nephron
 Secretion: by principle cell
TAL- ROMK recycle reabsorbed K+ into tubular lumen
DT- by Na-K ATPase pump (cation exchange) from interstitial
fluid to tubular epithelial cell(aldosterone), From cell to tubular
lumen by simple diffusion.
(In DT Na is also reabsorbed in association with H+ secretion, When total body
K+ high, H+ secretion inhibited and increase K+ secretion and vise versa)
  Major determinant of K+ secretion-
Aldosterone

Urinary flow
Distal Na delivery
Serum K level
Functioning apical K channel

Tubular handling of HCO3

 Reabsorption- 99.9 to 100% of filtered HCO3.
HCO3 reabsorption is a complicated process as it can not diffuse
freely
Site and Mechanism: throughout nephron except DLLH
PCT- 90%
DT, CT- 10-15%
 Excretion- 2-3 mmol/day through urine
 HCO3 generation in tubule- 70-100 mEq/day new HCO3 formed, it
does not represent the filtered HCO3
 B cell of corticle collecting duct secrete HCO3 by HCO3-Cl exchanger
which is important in metabolic alkalosis

Renal handling of Ammonia:

 Ammonia is produced within tubular epithelial cell
 From glutamine metabolism- 60% and other amino acid metabolism
40%
 Metabolism of glutamine also produces HCO3
 In PCT cell, production and secretion of ammonia occurs
 TAL- reabsorption of ammonia occurs for distal tubular acid titration

Steps:
Glutaminase
Glutamine +NH4 Glutamate +NH4
Glutamic dehydrogenase
       -ketogluterate +NH3
 
Renal handling of H ion
 Filtered load of H+ ion is very negligible
 H+ ion secretion occurs in all part of nephron except DLLH
 Secretion-
PCT-85% (Na-H exchange)
ALLH and DT- 18% (aldosterone induced cation exchange)
CD- 5% (Na- H exchange, H-K ATPase)

Fate of secreted H+ ion:

1. Secreted H+ reacts with HCO3 in the PCT and DT fluid causing
reabsorption of HCO3-
2. Secreted H+ reacts with dibasic phosphate (HPO 42-) in the DT and
CD to form monobasic phosphate
3. Secreted H+ ion reacts with NH3 to form NH4in the PCT and DCT
For each H+ ion excreted with PO4 or as NH4, there is net gain of
one HCO3- ion in the blood, replenish the supply of this important
buffer ion.

Table 1.4 Renal tubular buffer system

Buffer system Site of action

Bicarbonate buffer(HCO3 /CO2) -
PCT,DT
Phosphate buffer(HPO4 /H2PO4 )
2- -
DT, CD
Ammonia (NH3/NH4) PCT, DT

Acidification of urine
 Normal human urine pH: 4.5 to 8
 H2CO3 forms CO2 and H2O, then CO2 is expired, while Na appears in
the glomerular filtrate
 To the extend Na is replaced by the H+ ion in the urine, so Na ion
is conserved in the body.
 Major site of urine acidification:
DT

CT
  Steps of acidification of urine:
Secretion of H+ ion in the tubular fluid
HCO3 buffering( reabsorption of filtered bicarbonate)
Non-bicarbonate buffering (formation of titrable acid and ammonia)

Water reabsorption
 Passive reabsorption- PCT, thin DLLH
 ADH dependent water reabsorption- CT, CD
 Impermeable to water- ALLH and DCT

ADH
 Full name- antidiuretic hormone
 Synthesis- neuron of supraoptic and paraventricular nuclei of the
anterior hypothalamus.
 Transport and release- nerve ending of posterior pituitary gland
 Acts on- apical membrane of principle cell in the collecting ducts
causing increased water permeability through insertion of aquaporins
 Increased secretion of ADH-
Raised extracellular fluid osmolality
Dehydration

Hypovolumia

Hypotension

 DT, Collecting duct cell: 2 types

1. Principle cell- they are aldosterone sensitive, ENAC (Epithelial
Na channel))- expressing cells which also mediate water reabsorption
via ADH.
2. Intercalated cell- 2 types
a. Alpha –intercalated cell: tall, columnar cell, contains apical
H+ ATPase, it secrets H+(proton or acids)
b. Beta intercalated cell: shorter, flatter cell, contains apical chloride
bicarbonate exchanger (pendrin) which secretes bases
 Principle cell-
Aldosterone binds with the receptor and increases H+ ion secretion
both directly by increased expression of H+ ATPase and carbonic
anhydrase, indirectly by enhancing the luminal electronegativity
through Na reabsorption.
 Alpha intercalated cell of cortical collecting ducts
It secretes H+ through H+ ATPase and H/K ATPase which is
independent of Na transport. The hydroxyl (OH-) ions generated in
the cell through H+ secretion exit the cell by the HCO3-/Cl- exchanger
Congenital Anomalies of Kidney
and Urinary Tract (CAKUT) 02
Chapter

 Congenital abnormalities of kidney and urinary tract (CAKUT) occur

in approximately 0.1 to 6% of all live births, cause of 30%-50% of
ESRD by UTI, obstructive uropathy and renal damage.
 The kidney and urinary tract develop after the fusion of ureteric bud
and metanephric mesenchyme; a complex gene regulatory network
controls the molecular machinery of development.
 The ureteric bud gives rise to the ureters, renal pelvis, calyces and
distalpart of collecting tubule and metanephros to glomeruli and
tubules (proximal convoluted tubule, loop, distal convoluted tubule.
 Septation of the cloaca and ascent of the kidneys occur simultaneously.
 Metanephros (mesoderm) is penetrated by ureteric bud (endoderm)
which induces nephrogenesis from 10th to 36th weeks; number of
nephrons (1million in each kidney) is fixed for life. Thereafter size,
length and volume and functional maturation take place.
 Urorectal septum divides cloaca into urogenital sinus (bladder) and
rectum. Mesonephric ducts connect allantois to cloaca which opens
into urethra derived from endodermal urogenital sinus-bladder trigone.
Ramnant of allantois become fibrous urachus connecting bladder
to umbilicus.
 Association: Single umbilical artery, congenital heart disease (CHD),
external malformation, imperforate anus,scolious; so scan kidney.

Renal agenesis

Unilateral renal agenesis (single kidney): is caused by a failure of the

ureteral bud to communicate with the metanephric blastema in the first
few weeks of gestation.
 A number of cases of apparent renal agenesis will represent multicystic
dysplastic kidneys that have undergone spontaneous regression.
 The incidence of unilateral renal agenesis in the general population
and in prenatal studies is estimated at approximately 1:2000 and
1:800, respectively.
 Contralateral kidney show compensatory hypertrophy if not suspect
dysplasia, hence more probability of CKD.
  May occur in association with anomalies in other organ systems,
e.g. vertebrae, genitalia, intestines, anus, limbs, heart, trachea, ear
and CNS. Extra renal anomalies are found in 31%.
 The solitary functioning kidney may also have other anomalies
such as vesicoureteric reflux (24%), vesicoureteric junction obstruction
(20%), megaureter (7%), pelviureteric junction obstruction (6%), duplex
kidney(3%), renal cyst, ureterocele and posterior urethral valve (1%
each).
 On long term observation a higher population of patients with single
kidney shows hypertension (16%), proteinuria (21%) and low glomerular
filtration rate (GFR) (10%) with CKD.
 Diagnosis is now most commonly made on antenatal renal ultra-
sonography.
 Consider performing a DMSA scan to confirm absence of functioning
renal tissue and to look for ectopically sited kidney and MCUG
where ureteric dilation is present. MAG3 in PUJ with VUJ obstruction.
 Long term outcome is dependent upon the status of the single
kidney, however, annual review for hypertension, proteinuria and
serum creatinine is recommended.
 There is no restriction on participation in normal sports; collision or
full contact sports should be avoided.
 ACEI for hypertension, proteinuria reduction.
 Single kidney is found in 4 to 5% of first degree relative.
 Asymptomatic renal malformation found in 9%, hence USG is
indicated in 1st degree relative.
Bilateral renal agenesis: It is rare and almost uniformly fatal. Many fetuses
die in utero.
 The estimated incidence is 1 per 5000 fetuses.
 Fetal anuria results in oligohydromnios from around 16 weks
gestation, causing the potter sequence/facies/syndrome (characteristic
facial appearance with low set malrotated ear, facial nasal flattening
and underdeveloped chin) with severe pulmonary hypoplasia.
 Reduced intrauterine movement results in the development of arm
and leg flexural deformities.
 Death within hours of birth usually occurs secondary to pulmonary
hypoplasia.
 Diagnosis is confirmed by antenatal ultrasonograhy.
 Siblings should have renal US scan.
  Simple renal cyst found in 0.22%,asymptomatic, incidental detection,
no treatment required.But longitudinal follow up is needed to see
whether it is beginning of polycystic kidney disease and cystic conditions.Cyst
may be infected,may cause pain, fever.
 Multilocular cyst (multicystic nephroma): Benign, ± cystic wilmstumour.
Abdominal /flank mass is presentable. Need removal.

Renal hypoplasia

 Refers to a small kidney, which contains intact nephrons that are

reduced in number.
 Reduction in renal size to less than two standard deviation scores
below mean for age without scarring on DMSA scan and compensatory
hypertrophy of the contralateral kidney favors the diagnosis of
renal hypoplasia.
 Etiology is unclear, however, mutation in genes influencing ureteric
budding, fetal urinary tract obstruction and environmental influences
such as maternal diet are implicated.
 It may occur in association with vesicoureteral reflux, a genetic
syndrome or in isolation as a familial disorder.
 Congenital oligomeganephronia: is a form of renal hyoplasia
that is pathologically characterized by reduced renal size, absent
corticomedullary boundaries with only 5 to 6 renal pyramids and a
reduced number of meganephrons. The disorder is progressive
and leads to renal failure in early childhood. They are often born
premature, low birth weight. They present with polyuria, failure to
thrive. On histology, reduced glomeruli, large glomeruli.
Ask-upmark kidney- is small with deep grooves and lateral convexities,
segmental hypoplasia with decreased pyramids with severe hyper-
tension in girls. Vascular developmental defect, reflux nephropathy.
Glomeruli tubules are poorly differentiated, primitive, poorly functioning
or non functional.
 Treatment: Nephrectomy and control of hypertension.

Renal dysplasia

 Dysplasia includes aplasia, hypoplasia, dysplasia, hypodisplasia.

 It means differentiate abnormally. Multicystic dysplastic kidney
(MCDK) is the most common cystic renal malformation in children,
 nonfunctioning tissue, entire kidney ( many cyst), normally upper pole
of left kidney
 Developmental: Bud theory; failure of induction of ureteric bud to
differentiate mature mesodermal elements. So bydefinition, it can
only be unilateral in surviving infant.
 Resulting from failure of union of the ureteric bud with the renal
mesenchyme resulting in a non functioning kidney that is replaced
by large, non communicating cysts of varying size with no renal
cortex and an atretic ureter, contains undifferentiated tubules, cortical
fibromuscular tissue.
 Incidence of 1:2000 to 1:4000 live births. Twice as common in males.
 25% of cases have VUR and 3% has PUJ obstruction into the contra-
lateral kidney and genital anomaly, seminal cyst, Gardner cyst, blind
hemivagina. Also ureterocele, horseshoe shaped kidney, PUV. Incidence
of other CAKUT is 15%.
 Most frequently detected during antenatal ultrasonography (USG).
 Dysplastic tissue is frequently infected which spread and destroys
healthy renal parenchyma and hence has impaired function
 USG shows large non communicating cysts of varying size, no renal
parenchyma and atretic ureters. Differentials are hydronephrosis (HDN),
polycystic kidney.
 The contralateral kidney shows compensatory hypertrophy (defined
glomerulocystic as renal length >2 SD above mean) and VUR.
 DMSA scan will confirm absence of renal function on the affected
side.
 Micturating cystourethrogram (MCUG) should be considered if
there is evidence of calyceal or ureteric dilatation.
 Medullary cystic dysplastic kidney (MCDK) involute and are undetectable
by USG at 3 years and 5 year follow up, by 20% and 50% respectively.
Nottingham study reports 62% resolution at 10 yr.
 Nephrectomy may rarely be requird for (1) hypertension and (2) a
large cystic kidney (>6 cm diameter) which (3) fails to involute, (4)
repeated infection, (5) Wilm’s tumor. Laparoscopic to look for Wilm’s
tumor. Early nephrectomy (at 12 months) allow follow up, gives com-
paratively better outcome.
 Conservatively managed cases should be reviewed with annual
BP and urine dipstick testing for protein. Ultrasonography (USG)
should be annual until 2 years of life then repeated at the age of 5
 years if all is well.Involution by 10 years in 60% and involution in
35% by 15 years.
 Complication: Malignancy, raised blood pressure, infection, cyst
rupture, bleeding, chronic kidney disease(CKD)
 Mostly asymptomatic.

A: Renal agenesis B: Renal aplasia C: Renal hypoplasia

Figure 2.1: Renal developmental anomalies

Renal tubular dysgenesis

 It is a severe disorder characterized by a paucity of differentiated proximal

tubules.
 It may be genetic (primary) due to a mutation in the genes encoding
components of the renin angiotensin system; or secondary to twin
to twin transfusion, fetal hemochromatosis or fetal exposure to ACE
inhibitors.
 Clinical presentation is fetal/neonatal loss, potter sequence, anuria,
hypotension, defect with large fontanels and suture.
 Diagnosis is established by renal biopsy.
 The prognosis is unsatisfactory.

Medullary Sponge Kidney(MSK)

 It is not uncommon (1:5,000 to 1:20,000 populations) and being

asymptomatic, it is rarely detected during childhood.
 It is characterized by dilatation and cyst formation in medullary collecting
ducts, which gives the kidney a sponge like appearance. Cyst
 varies in size (1-3 cm), communicate with collecting duct. Cysts are
non-functional.
 May be associated with several syndromes (Marfan syndrome, Beckwith-
Wiedelmann syndrome, Caroli disease, Ehlers-Danlos syndrome,
etc.).
 It typically presents with recurrent stone formation, UTI, hematuria,
may be asymptomatic.
 Intravenous pyelography shows contrast in dilated medullary ducts
giving the impression of a brush or linear striation in the mild or a
“bouquet of flowers” in extreme cases.
 It usually has a benign course and does not cause progressive renal
failure.
 Microscopy; epithelium may be columner, cuboid, transitional or atrophic
in affected area.
 Recurrent calcification may be prevented by K+ citrate.
 Treatment of complication.

Ectopic Kidney

 Failure of ascent of the kidney during

embryogenesis.
 Occurs in approximately 1:1000 population.
 The ectopy may be simple (on the same
side) or crossed (on the opposite side).
 Most cases are pelvic kidneys, unilateral
or bilateral, rarely thoracic kidneys.
 Most case are asymptomatic, usually
have impaired function, hypoplastic, hydro-
nephrosis.
 It may occur in association with other
anomalies such as VUR, renal dysplasia,
cryptorchism, hypospadias, mullerian anomalies
or VACTERAL association. It is associated
with cloacal and anorectal malformation,
ureteric and lower tract malformation
 Evaluation includes estimation of serum
creatinine, DTPA scan and IVU
 Cardiac anomaly with charge syndrome Figure 2.2: Ectopic
association. kidney (left)
Crossed renal fused ectopia
 One kidney crosses the midline and lies in
abnormally rotated position, below and medial
to the normally sited one (figure)
 Incidence is 1:1000 to 1:7500.
 There may be fusion, the upper pole being
fused to the normal kidney’s lower pole.
 The ectopic kidney usually hypoplastic.
 It is often associated with vertebral, cardio-
vascular and gastrointestinal anomalies.
 The condition is asymptomatic and has a Figure 2.3: Crossed
good prognosis in large majority. renal ectopia
 In renal surgery- blood vessel is important
Left kidney to right side is common, adrenal gland does not cross.
 Few may have maternal ectopic kidney, hydronephrosis with CKD.

Horseshoe kidney
 The lower poles (95% of cases) of the kidneys are fused over the
midline by a narrow thick isthmus of functioning renal parenchyma
or thin fibrous tissue.
 The kidneys are sited more caudally than normal.
 Incidence 1:400 live births, more common in males.
 Often associated with hydronephrosis and urolithiasis (20%), PUJ
obstruction, VUR.
 The large majority are asymptomatic with
postmortem identification but may experience
abdominal pain or hematuria as a consequence
of stones or obstructive uropathy (PUJ obstruction,
HDN), UTI.
 May occur in patient with trisomy 13, 18, 21
and 22, Turner syndrome and VACTERL
association: Vertebral defects, anal atresia,
cardiac defect, tracheo- esophaseal fistula, renal
anomalies, limb abnormalities), more chance
of Wilms tumour, renal cell carcinoma, other
malignancies. MCKD has higher incidence.
 Imaging and radionuclide scanning are done Figure 2.4:
to assess for obstruction and differential Horseshoe kidney
 function- IVU, DTPA, MRU/CTU. And to confirm
the diagnosis and to detect ectopic renal
tissue, most suggest DMSA scan.
 Hypospadius and undescended testis in
4% of male.
 Bicornuate uterus on septate vagina can
be found in 7% female.
 Hypertension due to renal scarring by VUR,
dysplasia with obstruction.
Figure 2.5:
Duplex kidneys Duplex kidney
 Ureteric bud duplication
 Duplication of the collecting system is a common anomaly with incidence
of 0.8 to 5%) average 1% of population, familial, no significance.
 Unilateral duplication is more common (70% cases) than bilateral;
girls are more frequently affected than boys.
 Duplex kidney has two distinct pelvicalyceal systems with incomplete
(means divided pelvis, two ureters join before entering bladder) or
complete duplication of ureters, kidneys are usually longer (incomplete,
partial or uncomplicated duplex).
 If duplication is complete, the kidney has two moieties, each with
its own ureter: the upper pole ureter may be ectopic, draining into
the vagina or posterior urethra or may have ureterocoele; the
lower pole ureter may have VUR.
 Clinical features: Asymptomatic, dribbling from ectopia ureter, urinary
tract infection (UTI) invesico-ureteric reflux (VUR), obstructive uropathy
due to ureterocele.
 Continuous dribbling on urine.
 Infection in dysplastic tissues spread to normal renal parenchyma,
reducing functional renal mass
 Incomplete duplication results in uncomplicated duplex kidney,
with either simply a divided pelvis or two ureters that join before
entering the bladder.
 Classification of duplex kidneys recognizes the following types
based on the features of the upper moiety, which is appendant, embedded,
hydronephrotic, dual poor and dual well.
 Management options include renal preservation (antibiotic prophylaxis
for VUR, reimplantation of ectopic ureter) or renal resection based
on function of the renal moieties. Dysfunctional upper moiety needs
excision.
 Evaluation: USG, CTU/MRU, DTPA, Urine C/S, creatinine.
 Retrocaval ureter

 C/F: abdominal pain, infection, hematuria, urolithiasis in 2nd and 3rd

decade

Ectopic ureter

Ureter sites:
In boys: posterior urethra (50%), seminal vesicle (33%), vas deference, prostate,
epididymis
In girls: Urethra and bladder neck (33%), vaginal vestibule (33%), vagina
(25%), uterus, cervix.
Ectopic ureter inserted distal to external sphincter will cause incontinence,
mostly seen in girls causing vaginal and vestibular urine pooling. There
can be paradoxical incontinence despite normal voiding. Duplicated ectopic
ureter drains upper dysplastic non-functional renal moiety.
Diagnosis: USG, , IVU,CTU
Treatment : Resection of dysplastic renal moiety and ureterectomy.

Ureterocele

 It is a cystic dilatation of the terminal segments of the ureter in its

course in the submucosal layer of the bladder.
 It may be inside the bladder or outside it. Ureterocele may be a
single system or associated with a duplex system.
 Less commonly, ureterocele is ectopic, at the bladder neck or in
the urethra.
 Girls are affected more frequently and 10% cases are bilateral.
 UTI and obstruction are common complications.
 Cobra head appearance on IVU is diagnostic.
 Treatment consists of deroofing. Secondary VUR may require reimplan-
tation of the ureter. Ureterocele that produce bladder outlet obstruction
are managed by excision and reimplantation of the ureter.

Aberrant renal arteries/ veins:

 Source of raised BP, exercise causes postural hematuria, proteinuria,

flank pain, varicocele. It is due to compression of renal vessels
between abdominal aorta and superior mesenteric vein (nut cracker
syndrome). Surgical correction if symptomatic, consider a donar with
aberant vessel in renal transplant accordingly.
Patent urachus

 Persistent communication between the bladder and the umbilicus,

due to a lack of total obliteration of the urachus, is a common
abnormality.
 There is continuous discharge of urine through the umbilicus.
 The treatment is surgical.

Megacystic megaureter syndrome

 The bladder is very large and thin walled with massive vesicoureteric
reflux (secondary or primary)
 There is no distal obstruction to the passage of urine.
 The condition may be the result of severe primary VUR.
 Ureteric implantation is done in children with reflux. Patient with
non-obstructed and nonrefluxing system are managed conservatively.

Bladder exstrophy

 Exstrophy of the urinary bladder occurs in approximately 1 in

35,000-40,000 births. The male: female ratio is 2: 1.

Figure 2.6: Bladder exostrophy

  Anomalies of the bladder are hypothesized to result when the
mesoderm fails to invade the cephalad extension of the cloacal
membrane.
 In classic bladder exstrophy, the bladder protrudes from the abdominal
wall and its mucosa is exposed. The umbilicus is displaced
downward, the pubic rami are widely separated in the midline, and
the rectus muscles are separated.
 In boys, there is complete epispedias with dorsal chordee, and the
overall penile length is approximately half that of unaffected boys.
The scrotum typically is separated slightly from the penis and is
wide and shallow. Undescended testes and inguinal hernias are
common.
 Girls also have epispadias, with separation of the 2 halves of the
clitoris and wide separation of the labia. The anus is displaced
anteriorly in both sexes, and there may be rectal prolapse. The pubic
rami are widely separated.
 The consequences of untreated bladder exstrophy are total urinary
incontinence and an increased incidence of bladder cancer,
usually adenocarcinoma. In classic bladder exstrophy, the upper
urinary tracts are usually normal.
 Objectives of the management include (1) secure abdominal
wall closure, (2) urinary continence, (3) preserving renal function,
(4) creation of functionally and cosmetically acceptable external
genitalia.

Epispedius:
In girl a bifid clitoris or a urethral meatus which is patulous anteriorly is
diagnostic of epispadius. Epispedius in female with separation of pubis
symphysis and clitoris with patulous urethra is possible.Treatment is bladder
reconstruction and artificial sphincter.

Hypospadias
 Hypospadias occurs in 1 of 250 male newborn.
 The urethral meatus open on the ventral side of the penis proximal
to the tip of the glans penis.
 It is classified according to the meatal location: (1) glandular- opening
on the ventral aspect of the glans penis, (2) coronal- opening at the
coronal sulcus, (3) penile shaft, (4) penoscrotal, and (5) perineal.
About 65% of all cases of hypospadias are distal penile or coronal.
  Clinical finding include; hooded appearance of the penis, difficulty
in directing the urinary stream and stream spraying. Variable degree
of penile curvature (chordee) causes ventral bending and bowing
of the penile shaft, which can prevent sexual intercourse. Undes-
cended testicles or inguinal hernia may be present.
 Management: Newborns with hypospadias should not be circumcised,
because the preputial skin may be useful for future reconstruction.
Surgical repair is preferred between 6-12 months of age. Surgery
name is tubularized plate incised repair. Severe forms may be
repaired in two stages. Surgical construction aims at achieving a
straight penis and creation of a normally located cosmetically acceptable
urethral meatus.

Micropenis
 Micropenis is defined as a normally formed penis that is at least 2.5
SD below the mean in size.
 The pertinent measurement is the stretched penile length, which is
measured by stretching the penis and measuring the distance
from the penile base under the pubic symphysis to the tip of the
glans. The mean length of the term newborn penis is 3.5 ± 0.7 cm
and the diameter is 1.1 ± 0.2 cm. The diagnosis of micropenis is
made if the stretched length is <1.9 cm.
 Common causes include hypogonadotropic hypogonadism, hyper-
gonadotropic hypogonadism (primary testicular failure) and idiopathic
micropenis.
 Embedded penis of obesity
appears to be small, on
measurement it is of normal
length.
 Evaluation includes a karyotype,
assessment of anterior pituitary
function and testicular function,
and MRI to determine the anatomic
integrity of the hypothalamus
and the anterior pituitary gland
as well as the midline structure
of the brain.

Figure 2.7: Micropenis

Persistent cloaca
 Failure of development of urorectal septum.
 Urethra and vagina opening as a single channel
 Opening may be stenosed causing urine and uterine drainage
obstruction.
 Surgical separation of urethra and vagina, creation of vagina by
colonic tissue.

Absent abdominal musculature syndrome (previous eagle barret,

prune belly syndrome)
 Triad of
1. Deficiency or absence of anterior abdominal wall musculature.
2. Bilateral crytorchism in boys (95%)
3. Renal dysplasia, ureteric dilation- tortuosity
 VUR, kinking, obstruction (PUJ, VUJ)
 Bladder dilated, thickened, fibrosed, poorly contractile, multiple diverticula,
significant residual urine.
 Urethra narrow, atrectic

Others
 GIT: malrotation, gastrochisis, imperforate anus
 Cardiac: 10% has CHD
 Skeletal: CHD, Telepes
 Pulmonary

Phimosis (Non-retactile foreskin):

 All neonatal foreskin should be retracted to see free flow of urine
from external urethral orifice.
 At birth, glans penis is covered with prepuce, the meatus is not easily
visible and the prepuce is not retractable, due to normal preputial
adhesions that bind preputial skin to glans. If retractable in full then
it is not phimosis.
 Separation of the prepuce occurs due to keratinization of the subpreputial
epithelium at the end of 3 yrs of age, retraction of the foreskin occurs
in 90% (physiological phimosis).
  If physiological phimosis does not resolve by 3 years or the child
has dysuria, preputial dilatation and release of preputial adhesions
are carried out. It is done by lubricating the foreskin and glans and
then compression or corticosteroid cream twice daily for 1 month).
 True phimosis by scarring of recurrent balanoprostitis or congenital
is rare limiting the medical indication of circumcision.
 True phimosis causes preputial ballooning, urine flow obstruction,
UTI and renal impairement, should be circumcised.
Differentials: Meatal stenosis due to meatatitis, complication of circumcision;
instrumentation or congenital can cause urinary tract infection, stone, obstructive
uropathy and hence meataldilatation , meatotomy or meatoplasty are to be performed.

Meatal stenosis:
Always acquired and following circumcision,can have dysuria,frequency
hematuria can have hydronephrosis.Treatment is meatoplasty.

Prevalence of CAKUT in newborn:

 Congenital hydronephrosis: 1 in 1000 live birth
 Renal hypoplasia: 1 in 400 live birth
 Horshoe kidney: 1 in 1000 live birth
 Bilateral renal agenesis: 1 in 30000 live birth
 Posterior urethral valve 0.003%
 VUR: 1-2 in well child, 25-40% in UTI, with HDN 3-19%, 1-8% with
duplex ureter

Intra-uterine environment impact on CAKUT: Following infants in

intrauterine period and CAKUT (cause gene mutations):
 Low protein diet
 High/low sodium intake
 Cocaine, alchohol
 Vitamin A deficiency
 Hyperglycemia (maternal diabetes)
 Glucocorticoids
 RAAS blockade: ACEI decreases placental perfusion and inhibits
nephrogenesis. NSAID decreases renal perfusion may cause
CKD and cyst.
  MMF
 Antiepileptic drugs
 Cyclophosphamide
 Maternal folate deficiency (folate is necessary for DNA synthesis
and gene expression)
 Maternal obesity
 Malnutrition
 In vitro fertilization

Gene associated with CAKUT:

EYA 1
FRAS 1
FREM 1
FREM 2
CRIP 1
HNF 1B
PAX 2
SALL 1
SIX 1
SIX 5
WNT4

 Correct antenatal diagnosis is possible in 60-85% in 3 rd trimester

 25% of children born with CAKUT with bilateral disease will develop
ESKD by 1st two decade of life
 Risk factors of CKD are prematurity, LBW, severe neonatal and
postnatal renal insults
Table 2.1 Categories of CAKUT disorders

Type of Anomaly CAKUT Disorder Definition

Kidney number, Renal agenesis Unilateral or bilateral, kidney and
Kidney size and outflow system fail to form
morphology
Renal hypoplasia Unilateral or bilateral, kidney shape is
normal, but smaller in size and
reduced number of nephrons

Renal dysplasia Unilateral or bilateral, kidney shape

and tissue differentiation is abnormal,
reduced number of nephrons

Multicystic Multiple cysts within a dysplastic

dysplastic kidney kidney giving it an abnormal shape

Kidney position Horseshoe Kidneys are fused posteriorly forming

kidney a horseshoe shape

Ectopic/pelvic Kidney in an abnormal location,

kidney typically pelvic

Outflow Ureteropelvic Unilateral or bilateral, junction

abnormalities junction between kidney and ureter is
obstruction obstructed, preventing drainage of
urine from pelvis of the kidney

Vesicoureteric Unilateral or bilateral, junction

reflux between ureter and bladder is
defective, resulting in urine backflow
from bladder

Duplex collecting Unilateral or bilateral, duplication of

system ureter and kidney pelvis, can be
accompanied with duplicated kidneys;
outflow system may reflux or exhibit
obstruction

Megaureter Unilateral or bilateral, distension of

ureter resulting in defects in impaired
urine flow

Posterior urethral Membrane that forms in urethra

valves preventing emptying of bladder,
limited to males
 Table 2.2 Genetic risk factors for CAKUT

Type of Genetic Gene Function/ Gene Function/ Consequence

Anomaly Factor Consequence of of Mutation
Mutation
Single gene HNF1ß Transcription factor, Multicystic renal dysplasia, renal hypoplasia,
polymorphism autosomal dominant renal cysts, and diabetic syndrome

PAX2 Transcription factor, Renal hypoplasia, VUR, renal coloboma,

autosomal dominant FSGS

SIX1 Transcription factor, Renal hypodysplasia, VUR,

autosomal dominant branchio-oto-renal syndrome

SIX5 Transcription factor, Renal hypodysplasia, VUR,

autosomal dominant branchio-oto-renal syndrome

EYA1 Trascriptionalcoactivato Renal hypoplasia, branchio-oto-renal

r, autosomal dominant syndrome

SALL1 Transcription factor, Townes–Brocks syndrome, renal

autosomal dominant hypodysplasia

GATA3 Transcription factor, Renal dysplasia, hypoparathyroidism-

autosomal dominant deafness-renal dysplasia syndrome

FREM2 Integral membrane protein, Renal agenesis, Fraser syndrome

autosomal recessive

FRAS1 Extracellular matrix protein, Renal agenesis, Fraser syndrome

autosomal recessive

Copy number 1q21 Deletion or duplication Renal hypoplasia/dysplasia/cysts, PUV,

variants of region UPJO, VUR

4p16.1-16.3 Deletion or duplication Renal hypoplasia/dysplasia/cysts

of region

16p11.2 Deletion or duplication Renal hypoplasia/dysplasia/cysts, PUV,

of region UPJO, duplex collecting system, VUR

16p13.11 Deletion or duplication Renal hypoplasia/dysplasia/cysts, UPJO,

of region duplex collecting system

17q12 Deletion or duplication of Renal hypoplasia/dysplasia/cysts, PUV,

region, contains HNF1b UPJO, duplex collecting system

22q11.2 Deletion or duplication DiGeorge syndrome, renal

of region hypoplasia/dysplasia/cysts, UPJO, PUV,
dual collecting system, VUR
03
Chapter
Urine Analysis, Proteinuria
and Hematuria
Urinalysis:
 Urine analysis is a simple useful test aiding diagnosis of conditions
pertaining to the urinary tract.
 Urine should be examined fresh, preferably within 1 h of voiding. If
delay is anticipated, it can be stored at 4 °C in the refrigerator (4hour),
adding a few drops of acetic acid otherwise cells will disintegrate

Collection of specimen
 Midstream urine
- A clean catch midstream specimen is obtained after careful
local cleaning with water and soap. False positivity is 5-20%.
- The initial part of urine, which may still be contaminated with
periurethral bacteria, is discarded
- Opportunistic urine collection in a sterile cup is accepted when
parents refuse invasive catheter and supra-pubic aspirate
- Quick-Wee method: Supra-pubic area is stimulated by cold
water soaked gauze and then mid stream clean urine is collected
in a sterile cup
 Bag collection
- In neonate and infants
- It gives unacceptably high false positive results
- A negative culture helps to exclude UTI to a reasonable extent,
contamination rate is 60%-80%
- A higher threshold value of 100000 CFU/ml is regarded as
significant
 Suprapubic bladder aspiration: USG guided aspiration increases
probability of adequate urine in 60-97%. It is indicated when conta-
mination is likely, e.g., phimosis, valvovaginitis, ano-rectal anomalies
 Bladder catheterization, contamination rate is 10%
 Table 3.1 Contamination rate:

Method Contamination rate

Non-invasive methods:
Nappy pad >60%
Urine bag >50%
Clean catch >25%
Invasive methods:
Catheter 10%
Supra-pubic aspirate 1%

To avoid contamination, girls should sit toilet facing backward with legs
wide apart in uncircumcised boys retraction of prepuce may reduce conta-
mination. Soap and water cleaning can reduce contamination.
There are three screening methods of urine analysis:
1. Dipstick
2. Microscopy
3. Flow imaging analysis
High prevalent countries like Japan, Korea, Taiwan recommend screening
for hematuria, proteinuria but AAP does not.
Characterized by 3 aspects of urine:
 Physical examination
- Quantity
- Colour
- Sediment
 Chemical examination
- Specific gravity
- PH
- Protein
- Sugar
- Bile salt
- Bile pigment
- Ketone body
- Bilirubin
  Microscopic examination
- Pus cell
- Epithelial cell
- RBC
- Cast
- Crystal

Physical examination
Quantity
 10 ml is sufficient
Color
 Normally, colorless to clear yellow to amber depend on the concentration
of urochromes.
 The most common abnormal color observed in clinical practice is
red to brown urine
 The other urine colors are:
- White: phosphaturia, pyuria, chyluria
- Brown black: alkaptonuria (on prolonged standing), methemoglobin,
myoglobin
- Green: triamterene, amitriptyline, propofol, and pseudomonas
infection
- Blue: methylene blue
- Brown urine: chloroquine, nitrofurantoin
- Darkening on standing: imipenam, methyldopa, metronidazole
- Pink urine: uric acid crystalluria
- Orange: rifampicin, warfarin
- Cloudy: usually due to crystal formation on standing, uric acid
crystals form in acidic urine, phosphate crystals form in alkaline
urine; also due to WBC, cystine, struvite, refrigeration enhances
phosphate and urate precipitation
Odor
 Normally, the urine has an aromatic smell but can have a fetid or
foul smell due to urinary tract infection or as normal variation
 Presence of ketone: fruity smell to urine.
  Maple syrup urine disease: urine smells similar to maple syrup.
 Phenylketonuria: urine has a mousy smell.
 Isovaleric acidemia, glutaric acidemia: sweaty smell
 Tyrosinemia: rancid smell.

Chemical examination
Specific gravity
 A measure of urinary concentration (weight of the solution compared
with that of an equal volume of distilled water).
 Instrument used - urinometer/hydrometer. Bears a scale from
1.000 to 1.600.
 Normal range: 1.010 to 1.030.
- Isosthenuria, fixed specific gravity of 1.010.
- Hyposthenuria, specific gravity ≤ 1.007.
 A low specific gravityis found in diabetes mellitus (DM) , diabetes
insipidus (DI), renal tubular acidosis (RTA), nephronophthiasis and
other causes of polyuria
 A high specific gravity: inadequate fluid intake, dehydration.

Osmolality
 Measures number of solute particles per unit volume.
 Normal range: 40–1,500 mOsm/l.
 Useful in the diagnosis of patients with hyponatremia, hypernatremia
and polyuria (RTA, DI, Bartter, Gitelman, malfeeding, psychogenic and
others)

PH
 Normal, 4.5–7. It varies with food intake (lower pH with high protein
diet).
Proteins
 Methods
- Qualitative test
 Heat coagulation test (boiling test)
 10 % sulfosalicylic acid
 Dipstick methods
 - Quantitative test
 24 hrs urinary protein estimation (˃4 mg/m2/hr or ˃ 1gm/m2/day
indicates heavy proteinuria).
 Urine protein / creatinine ratio (values ˂ 0.2 insignificant, 0.2
-2 is significant and ˃ 2 indicate heavy proteinuria).

Causes of false positive proteinuria:

High concentrated urine
Alkaline urine (pH.8)
Gross hematuria
Pyuria, bactriuria
Dipstick left in urine too long
Delayed in reading dipstick
Contamination ( antiseptic, chlorhexidine)
Drugs- penicillamine, cephalosporin, sulfonamides
Urinary or vaginal secretion during UTI

Causes of false negative proteinuria:

Dilute urine
Acidic urine
Non- albumin proteinuria (light chain protein, globulin, LMW tubular
protein)
Reducing agents

Glucose
 Methods: Benedict’s test, dipstick method, clinitest tablets, and
enzymatic estimation using hexokinase.
 Benedict’s test detects reducing substances, not specific for glucose.
 Dipstick detects specific for glucose, specific gravity, pH, leukocyte
esterase, nitrite, protein, ketones, urobilinogen, bilirubin, blood and
hemoglobin.
 Lower level of glucose detection rate is 4- 5 mmol/ L.
Ketones
 Principle: based on a reaction of acetoacetate and acetone with
nitroprusside on the strip in the presence of glycine as the nitrogen
source
Microscopic examination
Pus cell
 Leukocyturia is defined as presence of more than 5 cells/HPF in
centrifuged urine or >10/mm3 in uncentrifuged urine. Pyuria means
an underlying “itis” (UTI, GN etc.)
 Boys over 3 year: 5-10 WBC/ml is significant
 Girls: 20-50/ml; suspect UTI, >50/µL definitely abnormal
 Bacteria may be clearly visible without Gram staining.
 Fungi with schistosoma can also be detected.

Epithelial Cells
 Epithelial cells may appear in the urine after being shed from anywhere
within the genitourinary tract. Three types of cells are seen:
1. Renal tubular cells: round/rectangular/polygonal/columnar, found
in ATN, rejection.
2. Urothelial cells: superficial/deep, represent desquamation.
3. Squamous cells: a constant finding, abundant cytoplasm, few
granules, small central nucleus, folded edges, usually found in
normal people.

RBC
 Phase contrast microscopy is the best, then, ordinary light microscopy.
 Presence of red blood cells (RBC) in urine and (>10 RBC per
mm3of freshly voided, unspun urine or >5 RBC per high power field
(HPF) of 10 ml of fresh urine, centrifuged at 2,000 rpm and resus-
pended in 0.5 ml.
 One ml of blood per 1 L of urine is sufficient to render urine visibly
“bloody.”
 Hematuria never causes anemia
 More than >5% acanthocyte may indicate glomerulonephritis

Casts
 Casts are elongated elements with a basic cylindrical shape. They
are formed in distal tubule and collecting duct. It consists of a matrix
of Tamm-Horsfall (TH) protein with or without entrapped cells.
 Hyaline casts: When none inside TH protein cylinder, found in
proteinuria with concentrated urine in normal person.
  Granular casts: When Tamm-Horsefall protein coats WBC, found
in UTI, GN.
 RBC casts: When it coats RBC.
 Epithelial casts: When Tamm-Horsefall coats epithelial cells.
 RBC cast indicates glomerular bleeding, WBC cast UTI, GN epithelial
cast (usually with WBC cast) indicates AIN, CIN with ATI

Crystals
 They are formed due to supersaturation of urine.
 Cystine, tyrosine, leucine, and cholesterol crystals are always pathological.

Urine Dipstick
 A urine test strip or dipstick test is a basic screening diagnostic tool
used to determine pathological changes in a patient's urine in standard
urinalysis. It is semiquantitative screening test, not qualitative (quantification
by UTP is the best)
 A standard urine test strip may comprise up to 10 different chemical
pads or reagents which react (change color) when immersed in, and
then removed from, a urine sample.
Nitrate reduction test:
 Screening test for UTI (sensitivity-83%, specificity-78% for E.coli
and other Gm-ve)
 Principle: Nitrate-splitting bacteria split nitrates in urine into nitrites
which react with an aromatic amine on the test strip, giving a
colored diazonium compound (red violet).
 If child urinates 1-4 hourly, sensitivity is 30-50%
 In girls its sensitivity is 98% because of long hold.
 Nitrituria + Leukocyturia: 93% sensitive in UTI detection
 False negativity if urine remains < 4hour in bladder
Leukocyte esterase test:
 Another screening test for UTI (sensitivity-55%, specificity-68%)
 Positivity increases by WBC or subprepucial material. It is negative
in concentrated urine or when urine contains collapsed WBC.
pH:
 Dipsticks can read pH 5–9. They are not accurate when pH <5.5
or >7.5.
Protein:
 Detects albumin and test is highly specific.
 Color change: pale green → green → blue.
Blood:
 Able to detect haemolysed and non-haemolysed blood in the
urine.
Glucose: specific for glucose.
 Based on glucose oxidase–peroxidase method, a double sequential
enzymatic method.
Ketones:
Urobilinogen
Bilirubin
Hemoglobin
Bacteruria
 Fresh urine should be kept at 4-80C during transportation to laboratory
or pre-incubated in culture media at 360C
 Bacterial colony count > 105/ml, 106 to 107/ml and any number in
bladder puncture
 False positive culture rate is 25%
 False negative culture rate in bag collection is 30-63%
 Culture media for uncommon pathogen like Chlamydia, Trichomonas,
Ureaplasma, fungus and viral are different
 TESTS AND READING TIME
SMALL MODERATE LARGE
LEU LEUKOCYTES NEGATIVE TRACE + ++ +++

2 minutes

NEGATIVE
NIT NITRITE POSITIVE
(any degree
60 seconds of uniform
pink color)

NORMAL mg/dL URINE (1 mg = approx. 1 EU)

URO UROBILINGOGEN 0.2 1 2 4 8

60 seconds

mg/dL 30 100 300 2000 or more

PRO PROTEIN NEGATIVE TRACE + ++ +++ ++++

60 seconds

pH pH 5.0 6.0 6.5 7.0 7.5 8.0 8.5

60 seconds

NON-HEMOLYZED HEMOLYZED SMALL MODERATE LARGE

BLO BLOOD NEGATIVE TRACE MODERATE TRACE + ++ +++

60 seconds

SPECIFIC 1.000 1.005 1.010 1.015 1.020 1.025 1.030

SG GRAVITY
60 seconds
TRACE SMALL MODERATE LARGE
KET KETONE NEGATIVE mg/dL 5 15 40 80 160

40 seconds
SMALL MODERATE LARGE
BILIRUBIN NEGATIVE ++ +++
BIL +

30 seconds

g/dL (%) 1/10 (ir.) 1/4 1/2 1 2 or more

GLU GLUCOSE NEGATIVE mg/dL 100 250 500 1000 2000 or more

30 seconds

Figure 3.1: Urine dip sticks

 Table 3.2 Reference range for leukocyte and bacteria (per µ/L and
ml respectively in uncentrifuged urine):

WBC count Spontaneously Midstream collection or Supra-pubic

voided Catheter collection aspiration
<3yr >3yr
Physiological <20 <15 <5 <5
Suspect 20-50 15-20 5-10 5-10
Pathological >50 >50 >10 >10
Bacteria count
Physiological <104 <103 <103 Sterile
Suspect 10 4
10 to 5×10
3 4
10 to 5×10
3 3
Sterile
Pathological >10 5
>5×10 4
>5×10 3
Any detection

PROTEINURIA
 Urine dipstick test detects presence of proteinuria; Biuret reaction
quantifies proteinuria and electrophoresis discovers type of proteinuria.
 Urine dipstick should be tested in freshly voided urine within 2 hours.
If refrigerated, it should be returned to room temperature before testing.
Positive dipstick means presence of heme (hemoglobin)
 Asymptomatic proteinuria (isolated without any other finding) found
in 0.6 to 6.3% of children
 Significant proteinuria may be found in 10% in single sample but in
2 sample, it is found in 2.5% and in 4 sample it is almost 0.1%.
 PCR/UTP is under and overestimated if urinary creatinine is very
high (>2.5 gm/L; e.g., among adoloscents and body buildres) or very
low (0.2g/L in muscular dystrophy) respectively
 Low molecular weight filtered by GBM, are reclaimed 96% in proximal
tubule
 If IgG/albumin quotient >3%, it is non-selective proteinuria
 For proteinuria detection 24 hour collection remain gold standard, because
1. Creatinine in the urine will be low in children with decreased muscle
mass and dilute urine
2. Machine measuring plasma creatinine may measure urine creatinine
inaccurately.
40mg/m2/hour roughly equivalent to 250 mg/mmol which is nephrotic
range.
 Microalbuminuria will not be detected by dipstick and labeled as
Ua:Ucr> 2.5mg/mmol
A Upr:Ucr of 100 mg/mmol or Ua:Ucr of >70mg/mmol is approximately
equal to 1gm/day.
Protein/creatinine is almostdouble albumin/creatinine (mg/mmol)
with glomerular proteinuria but even higher with tubular proteinuria.

Causes of proteinuria:
1. Intermittent/transient/physiological/insignificant:

Non-postural:
Fever
Exercise
Dehydration
Emotional stress
Cold exposure
Congestive cardiac failure(CCF)
Seizure
Hyperparathyroidism
Epinephrine
Unknown

Postural: (filtered out because of gravity)

Tamm Horsfall protein (50%)
Filtration of low molecular weight protein and albumun
Non-absorbable low molecular wt protein
 Orthostatic proteinuria moderate, non-selective proteinuria up to
1mg/mg creatinine in daytime and physiologic proteinuria may occur
during night
 It comprises 20-60% of all asymptomatic proteinuria; common in
adolescent and obese.

2. Fixed/pathological/significant /persistent proteinuria:

A) Glomerular:
Primary GN:
Minimal change nephrotic syndrome(MCNS)
Focal segmental glomerulusclerosis(FSGS)
 Mesengial proliferative glomerulonephritis (MPGN)
Rapidly progressive GN (RPGN)
 Membranous nephropathy
Congenital nephrotic syndrome(NS)
Other glomerulonephritis(GN)

Idiopathic/secondary GN:
Post infectious glomerulonephritis(GN)
Lupus nephritis
IgA nephropathy
Henoch Schonlein nephritis(HSP)
Alport syndrome
Other vasculitis and glomerulonephritis (GN).

Table 3.3 Proteinuria (threshold values)

Proteinuria measurements Timed sample Protein to creatinine

ratio (UPCR)
Normal urinary protein excretion <4 mg/m2 /h <0.2 g protein/g
(<100 mg/m2 /day)
Proteinuria >4 mg/m2/h >0.2 g/g
(>100 mg/m2/day)
Nephrotic-range proteinuria >40 mg/m 2 /h >2 g/g
(>1,000 mg/m2/day)
Microalbuminuria 30–300 mg/day 30–300 mg/g
20–200 mg/m2/day (0.03–0.3 g/g)

Table 3.4 Measurement of proteinuria:

24hour UTP PCR, mg/mg ACR, mg/G

Physiological <4 mg/m /hr or
2
<0.2 and <30
<100mg/day < 0.5 (6mon-2yr)
Proteinuria >4 mg/m2/hr or >0.2 and 30-299
>100mg/day >0.5 (6mon-2yr) (microalbuminuria)
Marked proteinuria >40 mg/m2/hr or >2 >300
>1gm/ m2/day (macroalbuminuria)
B) Tubular:
 Heriditary:
 Proximal renal tubular acidosis(PRTA)
 Dent’s disease
 Cystinosis
 Lowe syndrome
 Acquired:
 Pyelonephritis
 Interstitial nephritis
 Reflux nephropathy
 Acute kidney injury(AKI)
 Drugs
Increased production of plasma protein:
» Multiple myeloma, thalassaemia, rhabdomyolysis
Dipstick test: Urine dipstick should be tested in freshly voided urine
within 2 hours. If refrigerated, it should be returned to room temperature
before testing.

False positive:
High concentrated urine
Alkaline urine (PH > 8)
Gross hematuria
Pyuria, bacteriuria
Dipstick left in urine too long

Table 3.5 Proteinuria grading

Dip stick reading Urine protein concentration( g/l)

Trace 10-30 mg/dl

1+ 30-100 mg/dl

2+ 100-300 mg/dl

3+ 300-1000 mg/dl

4+ > 1000 mg/dl

 Table 3.6 Interpretation of dipstick test

Dip stick Color Urine protein mg/L

reading concentration( g/l)
Negative Yellow Insignificant
Trace Light yellow green <0.2 10-30, 150
1+ Yellow green 0.3 30-100
2+ Green 1.0 100-300
3+ Green blue 3.0 300-1000
4+ Blue >20 >1000

Delayed in reading dipstick

Contamination ( antiseptic, chlorhexidine)
Drugs- penicillamine, cephalosporin, sulfonamides
UTI

False negative:
Dilute urine
Acidic urine
Non- albumin proteinuria (light chain protein, globulin, LMW tubular
protein)
 A normal child can excrete 150 mg protein/day and in neonate
300mg/day. Microalbuminuria at lower concentration is found in
5-12% of healthy children.
1st morning testing urine for protein is good to avoid orthostatic
proteinuria
Insignificant proteinuria should be evaluated for 3 consecutive
mornings to exclude significant proteinuria.
Quantification dipstick detected proteinuria by 24 hour urinary total
protein.
A low albumin fraction in total excreted protein indicates extra-renal
proteinuria, e.g., hemoglobinuria, myoglobinuria, light chain proteinuria

HEMATURIA
 Persistent presence of more than 5 red blood cells (RBCs)/high
power field (HPF) in uncentrifuged urine.
 It occurs in 4–6% of urine samples from school-age children.
 1.5-2% of all children and adoloscents on repeat urine analysis
show hematuria
 Normal children can excrete more than 500,000 RBCs per 12-hr
period and increases with fever and/or exercise.
 The presence of 10-50 RBCs/μL may suggest underlying pathology,
but significant hematuria is generally considered as > 50 RBCs/HPF.
 Macrohematuria (<1000 RBC/ μL) is visible as red urine, microscopic
hematuria (RBC > 5-10/ μL) is visible by microscope only
 Macrohematuria is found in 1.3/1000 children, microhematuria is found
in 41/1000 children; common in boys (41/1000) than girls (14/1000)
 Microscopic analysis of 10-15 ml of freshly voided and centrifuged
urine is essential in confirming the presence of RBCs suggested
by > 10 RBCs/HPF, or a 1+ positive urinary dipstick reading.
 Microscopy of RBC must be prompt because of RBC lysis.
 Microscopy is mandatory to detect hematuria (RBC) with exclude
hemoglobinuria myoglobinuria positivity by dipstick (also detects
RBC)
 RBC cast is always pathological, signifies glomerular bleeding.
 Hemoglobinuria without hematuria can occur in the presence of
acute or chronic hemolysis.
 False+ve dipstick: Oxidising agent (bleaching powder), heavy bacterial
concentration, myoglobinuria, concentrated urine, hemoglobinuria.
 False negative dipstick: Dilute urine, vitamin C (reducing agent)
 1ml blood in 1L of urine makes it red- macro (gross) hematuria
 Microhematuria should be confirmed by multiple urine analysis (at
least 3)
 A positive dipstick is 73-89% sensitive and 81-93% specific (positive
dipstick means heme (Hb, myoglobin)
 Combined proteinuria and hematuria indicates underlying renal
disease and hence needs further evaluation
 Dysmorphic RBC (acanthocytes) or Micky-Mouse or RBC cylinders
(cast) indicates glomerular bleeding
 Presence of RBC >5% is 52% sensitive and 98% specific for
glomerular bleeding (GN, GP), >15-20% is significant.
 Sensitivity increases to 80% if 3 repeat different samples discloses
dysmorphic RBC
  RBC arises from glomerulus, cylinders (cast) in tubules and collecting
ducts
 Transient hematuria may not be pathological. It may be due to
fever, exercise (Jogger’s hematuria), but may be due to UTI,
stone, Wilm’s tumor.
 Girls can have RBC due to menstruation and intercourse.
 Persistent (3 times +ve) hematuria less common but signifies
underlying cause.
 Dip stick blood positivity may be due to myoglobin. Hemoglobin
and myoglobin are negative in urine for microscopy examination..
Other causes of red urine are both dipstick and microcopy negative
,only RBC is both dipstick and microcopy positive.

Causes of hematuria in children

UTI and GN are two common causes
Screen (1st urine analysis: RBC positive; 2nd and 3rd analysis positive)
needs further work up (isolated)

A. Upper urinary tract disease

Isolated renal disease
 Hypercalciuria (30-35% of hematuria)
 Immunoglobulin (Ig) A nephropathy (Berger disease)
 Alport syndrome (hereditary nephritis)
 Thin glomerular basement membrane nephropathy(TBMN)
 Postinfectious GN (poststreptococcal GN)
 Membranous nephropathy, membranoproliferative GN
 Rapidly progressive GN
 Focal segmental glomerulosclerosis
 Anti–glomerular basement membrane disease
 Hereditary angiopathy with nephropathy, aneurysms, muscle cramps
(HANAC)

Multisystem disease
 Systemic lupus erythematosus nephritis
 Henoch-Schönlein purpura nephritis (IgAVN)
 Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
 Polyarteritis nodosa
  Goodpasture syndrome
 Hemolytic-uremic syndrome
 Sickle cell glomerulopathy
 HIV nephropathy

Tubulointerstitial disease
 Pyelonephritis
 Interstitial nephritis (toxic nephropathy)
 Acute tubular necrosis
 Cystic renal disease
 Nephrocalcinosis
 Tumor

Vascular disorders
 Arterial or venous thrombosis
 Malformations (aneurysms, hemangiomas)
 Nutcracker syndrome
 Hemoglobinopathy (sickle cell trait/disease)
 Crystalluria

Anatomic disorders
 Hydronephrosis
 Cystic-syndromic kidney disease
 Polycystic kidney disease
 Multicystic dysplasia
 Tumor (Wilms tumor, rhabdomyosarcoma, angiomyolipoma, medullary
carcinoma)
 Trauma

Lower urinary tract disease

 Inflammation (infectious and noninfectious)
 Cystitis
 Urethritis
 Urolithiasis
 Trauma
  Coagulopathy
 Heavy exercise
 Bladder tumor
 Factitious syndrome, factitious syndrome by proxy (formerly Munchausen
syndrome and Munchausen syndrome by proxy)

Causes of gross hematuria

 Urinary tract infection
 Meatal stenosis with ulcer
 Perineal irritation
 Trauma
 Urolithiasis
 Hypercalciuria
 Obstruction
 Coagulopathy
 Tumor

Table 3.7 Glomerular vs non glomerular hematuria

Features Glomerular hematuria Non-glomerular hematuria
History
Urinary painless Dysuria, urgency,
symptoms frequency
Pattern of Total hematuria (bold Initial, terminal hematuria
hematuria throughout urinary stream)
Associated Sore throat, HTN, edema Fever, colicky pain
features
Family history Deafness, renal failure Renal stone, urinary
infection
Physical examination
HTN, edema Usually present Less common
Rash, petechiae, SLE, HSP Absent unless drug induced
purpura, arthritis interstitial nephritis
Urinalysis
Color Tea colored Bright red, blood clots
Proteinuria 2+ or more (>1 g/1) <2+ (<1 g/1)
Dysmprphic RBC >20% <15%, cumorphic
RBC casts Common Absent
Crystal Absent May be present

*Initial hematuria: Bladder cause and terminal hematuria: urethral bleeding.

  Glomerular disease
 Postinfectious glomerulonephritis
 IgA vasculitis (HSP)
 IgA nephropathy
 Alport syndrome (hereditary nephritis)
 Thin glomerular basement membrane disease
 Systemic lupus erythematosus nephritis.

Urethrorrhagia:
 Urethral bleeding in the absence of urine is associated with dysuria
and blood spots on underwear after voiding.
 This condition often occurs in prepubertal boys at intervals of several
months apart.
 It has a benign self-limited course.
 Less than10% of patients have evidence of glomerulonephritis.

Asymptomatic isolated microscopic hematuria

 Asymptomatic patients with isolated microscopic hematuria should
not undergo extensive diagnostic evaluation, because such hematuria
is often transient and benign.
 If it is persist for at least three urinalyses over a minimum of a 2-wk
period.
 Significant disease of the urinary tract is uncommon with this clinical
presentation.
 The initial evaluation of these children should include a urine
culture followed by a spot urine for hypercalciuria with a calcium:
creatinine ratio in culture-negative patients.
 Sickle cell screen should be included (in African-American).
 If these studies are normal, urinalysis of all first-degree relatives is
indicated.
Renal and bladder ultrasonography is useful to rule out structural lesions
(eg: tumor, cystic disease, hydronephrosis, or urolithiasis).

Causes of red urine (mimicking hematuria):

Food: Beet root, black berries, plums, cherry, food dyes; both dipstick and
microscopy negative
 Drugs: Rifampicin, nitrofurantoin, desferoxamine, chloroquine, sulfasalazine,
salicylate, adriamycin,metronidazole (both dipstick and microscopy
negative)
Pigments: Hemoglobinuria (black water fever), myoglobinuria, urate:
dipstick positive, microscopy negative. Uricite crystals cause pink
discoloration of nappies (brick red nappy)
IEM: Porphyria, alkaptonuria (both dipstick and microscopy negative)
Factitous: Munchausen by proxy: deliberate contamination.
Menstrual contamination
All discoloration except uric acid, remain so, for long time even after
centrifugation.

Causes of dark brown urine or black urine:

Hydroxyquinone
Methoglobinemia
Melanin

Causes of blue green urine :

Carotene
Riboflavin
Hepatitis
Obstructive jaundice
Blue diaper syndrome
Pseudomonas UTI

Causes of cloudy urine:

UTI (pyuria)
Uric acid
Calcuium phosphate crystal
Nephrotic syndrome
Radiographic dye
Calcium salts combination
Cysteine
Struvite
Precipitation of phosphate with urate enhanced by nefrigeration.
Red diaper syndrome: Gastroenteritis due to Serratia marcescens): Microscopy
positive, dipstick negative.
Milky white wine (chyluria): causes
Disruption of lymphatic channel (with chyle, fat)
Urinary albumin
Urine triglycerides
Partial nephrectomy
Tuberculosis
Tumors

Table 3.8 Difference between glomerular and tubular proteinuria

Parameter Glomerular Tubular

RBC Present Absent
HTN Common Usually absent
Low molecular weight Not Characteristic Usual
proteinuria
Azotemia More common Less common
Tubular symptom Absent Present
Prototype protein Albumin Retinol binding protein (RBP)
 Urinary Tract Infection (UTI) 04
Chapter

Introduction

 Urinary tract infection (UTI) is defined as the invasion and multiplication

of micro-organisms in significant number in urinary tract producing
symptoms
 5-14% of pediatric emergency visits are due to UTI
 Eight percent children (1-11year) experience 1 episode of UTI
 12-3-% of infant and children may have recurrent UTI
 Febrile UTI occurs in 10% of White and 2% of Black
 3% of girls and 1% of boys have symptomatic UTI before 11 yr,
50% of them recurrence by 1 yr.
 Upto 50% of UTI can have structural abnormalities

Epidemiology

 Varies with age, sex and race

 Incidence:
 Newborn
 Term: 0.5-1%

 Preterm: 3-5%

 Average: 1-4%

 Pre-school & school age:

 Girls 8.1%
 Boys 1.9%
 Bacteremia present in 6% cases
 Younger age group: M > F of because of higher incidence of
congenital anomalies
 M > F in neonate
 M = F in infant
 F > M in preschool due to short urethra,close proximity of anus
 2% of ESRD are due to UTI.
 Aetiology

A. Bacterial:
 E-coli: 80-90% of all UTI
 60% of first symptomatic UTI
 70% of recurrent UTI
 Proteus:
 30% of UTI in boys
 Others
 Pseudomonas
 Klebsiella
 Staphylococcus epidermidis
 Streptococcus faecalis
 Enterococcus
 Group B streptococcus
 Staphylococcus in CAKUT, genitourinary surgery, catheters and recent
antibiotic use
B. Fungal:
 Candida albicans
 Cryptococcus
C. Viral:
 Adenovirus.
D. Others:
 Chlamydia
 Mycoplasma
 Schistosoma haematobium

Classification:
A. Depending on severity and underlying defect
 Simple or uncomplicated
 Atypical/ complicated/severe : Acute pyelonephritis / underlying
obstructive uropathy/renal impairment/ non E.Coli/non responsive
to antibiotic by 72 hours/urosepsis/dehydration
 Atypical UTI/ complicated UTI:
 Severe acute pyelonephritis with or without obstructive uropathy,
with or without raised creatinine in severe urosepsis
 Does not respond with appropriate antibiotic within 2 days. These
children may have mass (pus collection) in bladder/kidney, it is
usually non E. Coli infection in obstructed urinary tract with some
renal damage
 UTI with any of the following:
1. Seriosly ill,
2. Oliguria,
3. Dehydration,
4. Retention,
5. Abscess,
6. Septicemia,
7. Raised creatinine (eGFR<80ml/min/1.73m2),
8. Non- E.Coli,
9. Failure to response by 72 hours (may be due to abscess,
occult obstruction with stone, indwelling bladder catheter).
10. Dyselectrolytimia
11. Obstruction of urinary tract.
B. According to region involved
 Upper UTI: Pyelonephritis, pyelitis, urethritis
 Lower UTI: Cystitis, urethritis
C. Symptoms present or absent
 Symptomatic
Acute pyelonephritis
Acute cystitis
Unspecified
Febrile

 Asymptomatic bacteriuria (ABU)

Asymptomatic bacteriuria (ABU)[common in neurogenic bladder]:

 When significant number of bacteria is found in repeated samples
of urine in a child who has no symptoms is called asymptomatic
bacteriuria.
  Incidence is 1-3%, prevalence 0-5%, usually resolves by months
to years
 Etiology:
E. coli – low virulent
 Treatment: not required
 Masked (occult) :
- Young kids with ill understood symptoms
- Non-specific symptoms
- Antibiotic for fever can mask
- May be culture negative
D. According to severity:
 Mild: Mild symptom, able to feed
 Severe: Fever, dehydration, vomiting
E. Recurrent UTI:
 More than 2 episode of APN or >3 episode of cystitis, or 1 APN + 1
cystitis
 Reinfection: UTI with different organism
 Breakthrough infection: UTI on antibiotic prophylaxis

Recurrent UTI
 Recurrent UTI can be defined as a second positive urine culture or
dipstick positive with symptoms within 2 or more weeks after the
termination of first UTI.
 Diagnosis: Based on clinical feature & culture of a properly collected
sample of urine, dipstick
 Culture yield is 30%
F. Presumed UTI: Symptomatic + positive urine analysis (bacteria, >WBC/HPF,
leukocyte esterase, nitrate
G. Definite UTI: Symptomatic, positive urine analysis (dipstick, microscopy),
urine culture positivity

Predisposing factors for UTI

A. Host:
 Infrequent & incomplete voiding with residual urine.
 Valvitis, prosthitis or balanitis
  Bowel bladder dysfunction(BBD): School going children inhibits bowel
and bladder resulting constipation, UTI, incontinence, encopresis, abnormality
of bowel, lower urinary tract can be present
 Obstructive uropathy and anatomical abnormalities (VUR), infrequent
voiding, stasis.
 Neurogenic bladder
 Constipation
 Uncircumcised boys: 10 times > circumcised boy
 In girls due to short urethra, anal proximity, coitus.
 Thread worm infestation
 Use of broad- spectrum antibiotic for minor illness
 Malnutrition
 Urethral instrumentation.
 Wiping from back to front in girl
 Tight clothings
 Bad perineal and preputial hygiene
 Toilet training
 Stone
 Pregnancy
 Tight underware
 P blood group: 80% of acute pyelonephritis (APN) , 21% of cystitis
has p fimbrae
B. Bacterial virulence:
 P. fimbriae - Adhesin
 O. Antigen
 K. Antigen
 Biofilm

Host defense against UTI

A. Normal periurethral flora
 Lactobacilli
 Low virulence: E-coli
 Enterococci
B. Bladder defense:
 Regular bladder emptying
 Intrinsic properties of the bladder epithelial cells to kill bacteria
C. Anti-adherence properties of urine:
 Tamm horsfall glycoprotein
 Secretary IgA
 Specific antibodies
D. Diet:
 Berry juices
 Fermented milk product
E. Breast feeding:
 Antiadhesive oligosaccharide
 Lactoferin
 Secretary IgA

Spread of Infection
A. Ascending infection – mostly
 Short urethra in female and infant boys
 Fecal soiling
 Voiding dysfunction.
 Manipulation.
B. Hematogenous: Unusual-except in,
 Neonates
 GI disease with peritonitis
 Sepsis
 Severely ill children with multi organ disease
 VUR is found in 1% of normal children, it is found much higher in
UTI
 It may be primary and secondary
 VUR is familial in 30-50% of instances
 VUR resolves 10% a year, UTI also decreases.
  Sting procedure (periureteric injection of bulking agents) has replaced
open reimplantation.

Pathogenesis of UTI:

 UTI can be ascending infection with or without obstructive uropathy

or disseminated blood borne sepsis.
 P-Fimbriae (pilli), lipopolysaccharide and hemolysin determine virulence
 Adhesin pap helps in adhesion of fimbriae to uroepithelium, fimbria
recognizes tall like receptor (TLR) in uroepithelium leads to release
of cytokine and local inflammation.
 Lipopolysaccharide (LPS) (endotoxin) contains lipid –A which
determines toxic effects including fever and acute phase response
 LPS binds with tall like receptor-4 in uroepithelium and renal tubules,
activation of receptors causes release of cytokines, chemokines, generate
reactive oxygen sepsis (ROS), recruitment of neutrophil and macrophages
 Inflammation tries, kills pathogen and damages tissue
 Inflammation is initiated by macrophages and completed by neutrophils
 Fibrosis and scar formation may occur
 Pathogenic E Coli produces hemolysin which exerts cytotoxic effect.
 Mannose receptors are present on the umbrella cells of bladder
cells where E coli replicate, also intracellular bacterial communicalus
(IBC) for intracellular reservoir and hence shed periodically and
cause recurrence.
 Permanent damage is more common with non E.coli UTI

Presenting features
In newborn:
Non specific, vague, sepsis, mortality around 10%
Presents with features of
 Septicemia,
 Hypothermia, fever
 Vomiting, lethargy,
  Persistence of physiological jaundice,
 Seizure,
 Shock,
 Grayish colour ,
 Failure to thrive.
 Refusal to suck
 Apnea
 Diarrhea, vomiting
 Oliguria, polyuria, AKI
 Malodorous urine
 Concomitant meningitis (1%)

In infant and young children:

 Unexplained fever, fever without localizing sign
 Abdominal pain
 Foul smelling urine
 Dribbling
 Voiding dysfunction.

In older children:
 Acute pyelonephritis(APN):
 Fever,
 Dysuria, hematuria, frequency, urgency, incontinence
 Abdominal pain,
 Back pain or loin pain or flank pain
 Nausea, vomiting,
 Positive bacteremia-sepsis (3-20%)
 Murphy’s punch sign positivity
 Full loin tenderness,
 Perinephric abscess,
 Toxic presentation
 Cystitis:
 Temperature -380C,
 Dysuria, frequent voiding, urgency,
 Hypogastric pain,
  Terminal hematuria
 Malodourous urine
 Daytime incontinence
 Post micturition dribbling
 Feeling of incomplete voiding
 Urethritis-
 Dysuria, dysuria without fever is often due to balanitis and valvitis
 Initial hematuria
 Holding manever (Vincents courtesy sign)
 Intermittent stream
 Voiding post-ponement
 Weak stream
 Incomplete bladder emptying
 Hesitency
 Straining
 Acute hemorrhagic cystitis by E coli, adenovirus, BK virus in transplanted
kidney, commonly in boys, usually self limiting by 4 days.
 Lower urinary tract symptoms (LUTs)

Sterile pyuria:
- Pus cell present in urine, C/S does not shows any growth.
Causes:
 Partially treated UTI
 Delayed inoculation causing bacterial autolysis
 Viral urinary tract infection (UTI)
 Renal TB
 Glomerulonephritis
 Acute interstitial nephritis (AIN )
 Sexually transmitted disease (STD)
 Appendicitis
 Crohns disease
 SLE
 Kawasaki disease
 Schistosomiasis
 Neoplasia
*Presence of >2 organism and non-pathogens are considered as contamination

Complications of UTI:
 Dehydration
 Dyselectrolytemia
 Urosepsis
 Abscess
 AKI by dehydration, nephrotoxic drug
 Complete occlusion of previous obstruction
 Renal scar: 3% after 1st UTI, 15% in febrile UTI, 29% after 3 febrile
UTI
 Scarring can cause later HTN, proteinuria, CKD: reflux nephropathy.

Reflux nephropathy:
 Renal cortical abnormality ,
 Damage with VUR
 VUR found in 23-30% of children with 1st febrile UTI and <10%
have grade IV and V.

Urine sample collection:

i. Pre-continent children:

Table 4.1 Collection methods

Method Contamination rate

Non-invasive methods:
Nappy pad >60%
Urine bag >50%
Clean catch >25%
Invasive methods:
Catheter 10%
Supra-pubic aspirate 1%

*USA general practitioner (GP) prefers invasive and UK GP’s prefer non-invasive
ii. Continent children:
 Mid stream clean catch opportunistic collection
 Initial void flushes flora from urethral orifice
 Cleaning with soap and water before collection reduces contamination
rate
 To avoid contamination, girls should sit toilet facing backward with
legs wide apart
*Quick-Wee method: Supra-pubic area is stimulated by cold water
soaked gauze and then mid stream clean urine is collected
There are three screening methods of urine analysis:
1. Dipstick
2. Microscopy
3. Flow imaging analysis: USG ,DMSA
4. Urine microscopy for WBC,RBC,cast and bacteria on Gram stain

Table 4.2 Interpretation of urine culture (see urine analysis chapter)

Method of collection Colony Probability of

count / ml infection
Suprapubic aspiration Any number 99%
Midstream clean catch >105 90 – 95%
Sample 104- 105 Very likely
103 - 104 Suspicious, repeat
103 or less Unlikely
Urethral catheterization >105 95 %
103 – 105 Very likely
103 or less Unlikely

Other investigations
 USG of kidney, ureter and bladder and post voidal residue (PVR) and
mean cystic capacity.In acute pyelonephritis enlarged echo bright kidney
with loss of corticomedullary differentiation is diagnostic aid.
 Blood count
  C-reactive protein (more likely to increase in APN)
 Blood urea & serum creatinine
 Blood culture in infants
 Procalcitonin (more likely to increase in APN)
 Pro-inflammatory cytokines
 Ferritin
 CSF study in urosepsis in younger kids
 Creatinine, electrolyte
 Lactate
 VCUG should be done if sonologic dilatation persists after 4-6
weeks
 Urinary IL-6 and NGAL may be used to differentiate ABU from UTI
 Lumber puncture and CSF study in young kids with urosepsis.
 All UTI should undergo USG of KUB with PVR and MCC, if high
PVR, pelvicalyceal dilatation; MCU with RGU is recommended

Table 4.3 Urinalysis and newer screening tests

Test Sensitivity (%) Specificity (%)

Leukocyte esterase 83 78
Nitrite 53 95
Leukocyte esterase with nitrite 93 72
Leukocyturia 73 81
Bacteria 81 83
Gram stain 93 95
Catalass 86 95
Lactoferrin 93 75
Bioluminescence 96 70
Turbidimetry 9 55
Esterase+nitrate+microscopy 99 70
 which is best for lower tract evaluation. Better after 4-6 weeks of
UTI resolution because of toxin dilatation during acute infection
 E. Coli endotoxin may cause dilatation which appears to be hydro-
nephrosis
 Edema may change size and shape of kidney and echogrnicity of
parenchyma
 Ureter can be better evaluated by CT urogram, MR urogram
 DTPA/MAG3 renogram evaluate renal parenchymal function, obstruction
by its 3 phase study, in APN it is diagnostic ,can assess GFR precisely.
 DMSA after 3-6 months can detect scar, functional tissue, diffusion
weighted MRI diagnose APN
 Structural anomaly detection rate is 15% of UTI, of which 1-2 %
may require surgery, it is the reason to image in patients with UTI.
 Dipstick leukocyte esterase and nitrite are useful screening test
 Symptom positive plus dipstick esterase and nitrite positive plus
pyuria diagnose UTI with 98% probability
 APN-cystitis differentiation by CRP, procalcitonin may or may not
be possible.
 Absence of common alternative diagnosis for fever, mostly
respiratory tract, UTI should be an important consideration

Treatment
 Empirical antibiotic should be started after sending urine for
culture, then antibiotic according to culture sensitivity
 Current PO choices are cefuroxime, co-amoxicillin, cefixime, ceftibuten,
quinolone, cefaclor, cefalexin

Duration of treatment
 For complicated UTI : 10 – 14 days
 For simple UTI : 7 – 10 days
 Shorter duration of treatment regimen is not recommended in
children.
 Following initial treatment, prophylactic antibiotic therapy should
be started in children below 2 years of age until appropriate imaging
of the urinary tract is completed.
Table 4.4 Recommended imaging test:

Recommended imaging test(s)

National institute for health and clinical excellence (NICE) UK
Age 0-6 months
Uncomplicated first UTI Outpatient ultrasound.
Atypical UTI Inpatient ultrasound, outpatient DMSA
scan and VCUG.
Recurrent UTI Inpatient ultrasound, outpatient DMSA
scan and VCUG.
Age 6 months-3 years
Uncomplicated first UTI No imaging.
Atypical UTI Inpatient ultrasound, outpatient DMSA scan.
Recurrent UTI Outpatient ultrasound, outpatient DMSA scan.
Age >3 years
Uncomplicated first UTI No imaging.
Atypical UTI Inpatient ultrasound.
Recurrent UTI Outpatient ultrasound, outpatient DMSA scan.
American Academy of Pediatrics (AAP)
Age 0-24 months
Any febrile UTI Ultrasound.
Complex or atypical circumstances VCUG.
Recurrent UTI Further evaluation.
Canadian Pediatric Society (CPS)
Any febrile UTI aged <2 years Ultrasound.
European Associated of Urology/European Society for Pediatric Urology
Any febrile UTI Ultrasound.
Suspicion of VUR and/or pyelonephritis VVCUG and/or DMSA scan.
Spanish Association of pediatrics
UTI that requires admission, is recurrent Inpatient ultrasound.
or with suspected complications
First UTI if aged <6 months Outpatient ultrasound.
Recurrent or atypical UTI Outpatient ultrasound, and VCUG or
contrast enhanced bladder ultrasound
especially if aged <6 months, and
DMSA scan especially if aged <3 years.
  PO antibiotic as per culture sensitivity and in vitro response
pattern.
 Current and local sensitivity is important.
 Fever resolves by day 1 in 2/3rd, 42% by day 3, fever beyond 3
days means abscess, resistant organism or uncommon organism

Indications of IV antibiotic:

 Unable to take orally

 Too toxic child (APN)
 Less than 3 month age
 Atypical/complicated UTI
 Immunocompromised
 All oral resistant antibiotic
 Abscess (renal, perinephric)
 Non compliance
 IV choices are- ceftriaxone, ceftazidime, ampicillin+gentamicin, cefipime,
meropenem etc.

Indication of surgery:

 Abscess drainage
 Obstructive lesion
 Grade IV, V VUR

Indications of prophylaxis in UTI

 UTI with obstructive uropathy until relieved
 VUR until resolved
 AAP and Canadian Pediatric Society are reluctant to recommend
prophylaxis because of higher incidence of breakthrough UTI.
*In vivo and vitro sensitivity may not be always same, clinical response by
3 days is more important
 Broad spectrum antibiotics are discouraged as prophylaxis

Long term follow-up

 Children with renal scar detected by DMSA should be in continued
follow up twice a year.
 Antibiotics for low dose prophylaxis against urinary tract
Table 4.5 infection

Antibiotic Recommended Resistant bacteria

dosage that may cause
(mg/kg/24h) breakthrough
infections

Nitrofuratoin 1 Klebsiella

Trimethoprim 0.5 Staphylococcus

Trimethoprim sulfonamide 0.5 S epidermidis

Cefadroxil 3-5 Enterbacteria

Ciprofloxacin 1 Enteroccoci

Cephalexin 10-12 Enterocci

Cefixime 2 mg

 Physical growth monitoring (height, weight)- every 6 months

 Blood pressure monitoring- every 6 months
 Investigations (in selected cases):
a) Urine-analysis for proteinuria – every 6 months
b) Urine culture promptly if features of UTI present
c) Blood level of new biomarker & creatinine – every 6 months
d) Ultrasound to monitor renal growth – every year
e) MCU - every 12-18 months
f) DMSA scan - if breakthrough UTI
 Measures to reduce recurrent UTI
 Perineal and preputial hygiene
 Circumcision but 100 circumcisions are needed to prevent are
one UTI
 Attention to undergarments and perinealhyegiene
 Plenty of fluid intake and frequent voiding
 Avoidance of constipation
  Double voiding training
 Early intervention of obstructive uropathy
- Cranberry juice, syrup
- Prophylaxis prevents recurrence but not scarring

Infection of foreskin (prosthitis) with glans (balanitis):

 Bacterial /soap-detergents caused inflammation
 Responsible bacteria are: Streptococus, Staphylococcus, Proteus
and other Gm negative and yeast.
 Urine have only WBC with bacteria.
 Most cases are self limiting
 Topical steroid result in rapid resolution.
 Treatment:Antibiotic, anti fungal and steroid ointment for bacteria ,
fungal and inflammatory cause.
 Severe cellulitis may need systemic antibiotics and circumcision
(after infection control) in recurrent infection.
 Infection /inflammation of glans (prostatitis) can coexist. Treated in
same fashion.
Paraphimosis : It caused by retracting tight foreskin over the gland may
cause glandular oedema and swelling. It is to be reduced carefully with or
without anesthesia.

Medical indications for circumcision

1. Severe acute or recurrent balanoposthitis
2. Penile malignancy
3. Trauma foreskin injury when foreskin cannot be salvaged
4. Balanitis xerotica abliterans: non infective hard fibrotic foreskin
5. CAKUT with recurrent UTI

Complications:
 Bleeding
 Infection
 Poor would healing
 Injuring to glass, urethra
 Mental stenosis
 Vulvovaginitis
 Prepubertal girls are commonly affected
 Soreness, itching, discharge, bleeding
 Dysuria, frequency
 Inspection: inflammation of the labia with introitus and discharge
Aetiology:
 Poor wiping method
 Constipation followed by soiling
 Welting
 Friction from wet/nylon underwear
 Bubble bath/detergents
 Infection (in 20% of cases)
 Bacteria (GABS, Staphaureus, H influenza)
 Thread worm (Enterovirus vermicularis)
 Fungal
 Viral
 STD
 Oestrogen deficiency
 Skin disease: Eczema, lichen sclerosus
 Foreign body
 Sexual abuse
Investigation: Urine R/E, C/S, swab from introitus
Management:
Po antibiotic
Empirical metronidazole
Local antifungal
Oestrogen, steroid ointment
Management of etiological factors
 Acute Glomerulonephritis 05
Chapter

Post Infectious Glomerulonephritis (PIGN)

 It is a classic example of the acute nephritic syndrome.
 Immunologic injury to the glomerulus.
 Most common glomerular cause of gross hematuria.
 Characterized by:
Sudden onset of hematuria (microscopic or macroscopic).
Hypertension.

Mild azotemia.
Oliguria.

Edema.

 Declining incidence, still the most common cause of glomerulonephritis

in USA and west, 97% occur in poor areas of globe.
 Common cause of kidney injury in the Middle East, Africa, Australia,
and Worldwide.
 Annual incidence rate ranges from 6 to 28 per 100000 person per
year in less developed nation to < 1 person per 100000 in developed
nation.
 Annual worldwide burden is 47,000 cases.
 Under recognition of milder cases are common.

Etiology of PIGN

Bacteria:
 Group A β hemolytic streptococci (GAS) responsible for > 95%
of PIGN. Rarely group C & G can cause post streptococcal PIGN
(APSGN).
 Other post infectious bacterial GN are:
Pneumonia – Pneumococcus, H influenzae, Mycoplasma pneumoniae
Enterocolitis – non typhoidal Salmonella, E. coli, Campylobacter jejuni
 Abscess, cellulitis- Staph aureus
Infective endocarditis – Staph aureus > 50%, Staph epidermidis,
Streptococcus viridens, Streptococcus pyogens, Enterococcus
faecalis, Gm –ve e.g., Proteus, E coli
Shunt nephritis –Staph epidermidis
Mycobacterium tuberculosis
Neisseria meningitis
Nephritogenic and rheumatogenic GAS can coexist.

Virus/Rickettsia/Fungus/Parasite: can cause post infectious GN

(PIGN)
 Influenzas
 Hepatitis (B, C)
 Human immunodeficiency virus (HIV)
 Measles, Rubella
 Ebstein bar virus (EBV)
 Cytomegalovirus (CMV)
 Varicella
 Parvo virus
 Herpes simplex virus
 Rickettsial –Rocky Mountain spotted fever, Q fever.
 Fungal - Candida albicans, aspergillus, cryptococcus, pneumocystis
carinii, nocardia.
 Parasitic – malaria (Pmalariae, P falciparum), filariasis, leishmaniasis,
schistosomiasis, trypanosomiasis, Toxoplasma gondi.

Risk Group
 Socio-economically disadvantageous children.
 Overcrowding.
 Geriatric population with comorbidities like diabetes, HIV infection,
CKD alcoholism IV drug user, malignancy
 Genetic predisposition HLA DR4 and DR1 identified gene (found
in 5- 28%). 40% can have family history
 Inadequate healthcare with other basic needs
  Indigenous/ aboriginal people of Australia, Canada,Māori people
of New Zealand
 More common in elderly people.
 Epidemic outbreak in risk group.

D/D of PIGN
 Vasculitis:
1. Systemic lupus erythematosus (SLE)
2. IgA vasculitis (Henoch–Schönlein Purpura)
3. Antinuclear cytoplasmic antibody (ANCA) associated vasculitis
4. Goodpastures syndrome

 Acute exacerbation of chronic GN

1. C3 GP
2. MesPGN
3. Alport syndrome

 Others: (rare AGN like presentation)

1. DPT vaccines
2. Guillain Barre syndrome (GBS).
3. Serum sickness.
4. Cryoglobinaemia.
5. Hemolytic uremic syndrome (HUS).
6. Acute interstitial nephritis.
 IgA-dominant-infection related glomerulonephritis (IgADIRGN)

Acute poststreptococcal glomerulonephritis (APSGN)

 Most common – group A β hemolytic streptococcus (GABHS) comprises
> 95% of PIGN.
 ASPGN is mediated by type-III immune complexes reaction and
depression in the serum complement (C3) level provide strong
evidence.
 Declining incidence in rich nations, still exist in resource poor nations,
aboriginal of Australia, Canada, indigenous Māori and pacific islander
of NZ
 Annual incidence ranges from 6 to 28 per 100,000 person years in
less developed nations, 0.9 (<1) person per 100,000 in developed
nation.
 Under recognition of milder transient cases are common
 Annual worldwide burden is 470000 cases.
 More common in elderly population with comorbidities like diabetes,
CKD, bed sore because of inadequate hygiene and immuno-
compromised state (4 per 10000 adult person)
 5-6-fold increased CKD risk.
 Epidemic outbreak in risk group.
 Nephritogenic strain of GABHS for pharyngitis (M-1,2 and 25) in
winter session and nephritogenic strain of GABHS (M49) following
skin infection (pyoderma) in warm weather being commonest cause
of PIGN.
 Other strain types are 1,18, 24 & 25 for throat infection and type
55, 57, 60 for pyoderma
 Nephritogenic with rheumatogenicstrains can coexist.
 Two common nephritogenic antigens are SPEB and NAPlr
 Streptococcal pyrogenic exotoxin B (SPEB).
 Nephritis associated plasmin receptor (NAPlr) – it is a glyceraldehyde
3 phosphate dehydrogenase with plasmin binding capacity, more
often found in Japan. Ab to NAPlr detected in 92% of convalescing
PSGN and 60% of uncomplicated streptococcal infection.
 M protein is not nephritogenic
 Endostreptosin.
 Preabsorbing antigen.
 SPEB and NAPlr are common two nephritogenic toxin involved in the
APSGN pathogenesis, commonly found in Europe and Latin America.
 Risk of APSGN after GAS infection 15%.
 Risk is 5% in throat infection to as high as 25% in pyoderma.
 Subclinical infection 1.5 times more than overt APSGN, subclinical
disease is characterized by hypocomplementemia, microscopic
hematuria and normal or increased BP in asymptomatic patients.
 Asymptomatic contact can have microscopic hematuria.
Pathogenesis of APSGN
Type III immune complex reaction
streptokinase
1. Plasminogen Plasmin.
2. Streptococcal antigen enters into blood stream incite antibody.
Preformed Ag-Ab immune complex formed in the circulation deposit
in glomerulus due to molecular mimicry
3. Antigen trapped/ planted in glomerulus began to interact with the
newly formed circulating antibodies to form immune complex in
situ. Ab binds to cross reactive renal Ag or trapped streptococcal
Ag or structurally homologous renal protein (molecular mimicry)
causing in situ immune complex formation ultimately which leads
to complement activation, recruitment and activation of monocyte
and neutrophil. This causesrelease of cytokines, proliferation/
hypercellularity of endothelial / mesangial with inflammatory cells.

Figure 6.1: Gross hematuria in ASPGN

4. Crescents and interstitial fibrosis are seen rarely.
5. IF :Lumpy –bumpy deposition of Ig and complements.
6. EM : Electron dense deposition
Glomerular Inflammation leads to less permeable GBM causes
water and sodium retention increases volume which leads to down-
gradingrenin angiotensin aldosteronesystem (RAAS) activity, atrial
natriuretic factor (ANF), prostaglandin (PG).
In response to glomerular inflammation and impaired filtration leads to
increased ENaC activity, decrease RAAS activity, decrease prostaglandin,
decrease kallikrein.
Subepithelial lump is characteristics.
 Clinical presentation

A) Typical:
 All ages, more common in 4-15 years and above 60 yrs., mean 7
years, school-age common, overcrowded living, and poor bracket.
 Male: Female = 2:1 to 4:1
 Abrupt onset.
 Occurring 7-14 days following pharyngitis or 3-6 weeks following
skin infection.
 Asymptomatic: 50%, subclinical 4-19 times common than overt
 Acute fluid overload:
- Peripheral edema (75-90%), periorbital may disappear at the
end of the day. Ascites is uncommon
- Pulmonary edema (14%).
- Congestive heart failure (2%).
 Hypertension (60-90%).
 Hematuria:
- Microscopic 90-100%.
- Gross 40-60%.
 Proteinuria; mild to moderation- common, up to 80%
 Nephrotic presentation; 4-10%.
 Renal function:
- Transient oliguria.
- Mild to moderately raised creatinine (40% to 45%).
 Nonspecific: anorexia, malaise, nausea, vomiting
B) Atypical: subsequent clinical evaluation may reveal typical APSGN
 Subclinical
 Severe disease - rapidly progressive glomerulonephritis (RPGN);
nephritic-nephrotic presentation
 Disease with normal urine analysis or no symptom with abnormal
urinalysis. Delay in urine examination can cause RBC lysis with negative
report.
  Extrarenal presentation suggest IgA vasculitis/ SLE/ other diagnosis
 History of blood transfusion.
 History of substance abuse.
 History of immunocompromised status (diabetes mellitus, hypertension,
heart disease, malignancy, kidney transplantation).
 History of deafness.
 Family history of glomerulonephritis, autoimmune diseases, kidney
failure, hypertension.

C) With complications:
1. Heart failure – LVF followed by CCF, pulmonary edema may simulate
pneumonia.
2. Hypertensive encephalopathy(10%), pulmono-renal symptom of
GPA, SLE, MPA, IgAVN
3. AKI incidence ranges 3 to 50%, 30% in average.
4. Posterior reversible leukoencephalopathy syndrome (PRES).: CNS
feature including headache, convulsion, blurred vision, altered cons-
ciousness, visual hallucination, mental disturbance, neuro- psychiatric
symptom
5. RPGN <1%
- Oliguria to anuria.
- Acute profound renal insufficiency with more than 50% glomeruli
with crescents.
6. Electrolyte abnormalities: low TCO2, high K+, Na+ normal/low/high,
decreased Ca, increased PO4.
7. NS: 2-4%
8. CKD: 1 to 2% in long term in children, 3-5% in adult.
1% can have persistent abnormal urinalysis, low C3, high creatinine
(C3 glomerulopathy remain as differential diagnosis)

Differential diagnoses of APSGN

 Nephrotic syndrome: atypical presentation

 Other post infectious glomerulonephritis (PIGN): bacterial, virus
and fungal.
  IgA nephropathy: shorter latency 2-3 days (synpharyngitic)
 C3GP/MPGN and other acute on chronic GN (C3 GP is also syn-
pharyngitic)
 Alport disease.
 SLE, and other vasculitis.
 IgA Vasculitis nephritis (IgAVN))
 Acute interstitial nephritis.
 HUS
 ANCA associated vasculitis
 Goodpasture disease has lung disease, positive anti GBM antibody

Natural history of APSGN

Acute phase usually resolves within 6-8 wks. Persistence of sign symptoms
beyond 8 wks may suggest alternate diagnosis.
 BP returns normal – within 2 weeks, may need 4-6 weeks
 Oliguria resolves – within 2 weeks.
 Azotemia – within 2 weeks.
 Gross hematuria resolves by 4-8 weeks.
 Massive proteinuria resolves by < 2 weeks.
 Moderate proteinuria resolves by < 6 months.
 Microscopic hematuria resolves by < 1-2 year.
 Complement level normalizes by < 3 month.
 CKD develops in 1% of APSGN.
 1% can have mild proteinuria, hematuria, hypertension. CKD is possible
in long term.

Investigation
 Urinalysis:
1. Urine routine examination, culture and colony count
a. Dysmorphic RBC.
b. RBC cast.
c. Pus cell (indicate inflammation).
d. Mild to moderate proteinuria.
2. Protein creatinine ratio: Non nephrotic range
 Bacteriology/Serology:
a. ASO titre (>333 todds unit) – rises in 90%.Rising titre is suggestive,
starts to rise 1-2 weeks, peaks by 4 weeks, gradually falls at 12
weeks, elevated more in post pharyngitis APSGN.It is found raised
in 20% of normal population.
b. Throat swab for C/S.
c. Streptozyme assay: anti-streptolysin O, anti-DNAase B, anti-
hyaluronidase, anti-streptokinase, anti NADase; it is most
sensitive (97%) and specific (80%).
d. Anti NaPlr (plasmin associated receptor) is measure of protection,
found in 60-92% of APSGN.
e. Anti NaPlr and anti SPEB-SPEB titrehave higher specificity
f. Anti DNAase B increases more in post pyoderma APSGN
 Immunology:
a. C3 and C4: C3 depressed in APSGN, both decreases in SLE,
low CH50 in 60% APSGN
C3 falls before rising of ASOT, and normalizes within 6-8 wk.
15-30% APSGN can have low C3 & C4
b. To exclude vasculitis (SLE / ANCA associated)
Anti-nuclear antibody (ANA).
Anti-ds DNA.
Anti-nuclear cytoplasmic antibody (ANCA).
 p-ANCA or MPO: microscopic polyangiitis
 c-ANCA or PR3: granulomatosis with polyangiitis
Anti GBM antibodies- Anti GBM disease, Goodpasture’s disease
c. Anti-factor B levels: It is a component of the alternative C3 convertase.
Present in >90% of children with acute post infectious glomeru-
lonephritis, distinguishing it from cryoglobulin with C 3 GP.
 Renal function and electrolytes:
a. Serum creatinine, cystatin C, other newer biomarkers.
b. Serum urea / blood urea nitrogen (BUN).
c. Serum electrolytes: raised K+, decreased TCo2, dilutional hypo-
natremia. are common
d. Blood gas analysis – if acidotic breathing.
  Hematological:
a. Full blood count: Increased polymorphonuclear leukocytes
(PMN) in APSGN.
b. Peripheral blood film – to exclude alternate diagnosis, low grade
hemolysis, dilutional anemia possible, normal film is common.
 Radiological:
a. CXR – To see pulmonary edema, cardiomegaly, pleural effusion
b. USG of KUB – To exclude chronic GN.
c. MRI of brain (T2 weighted): if PRES is suspected, hyoerin-
tense area in parieto-occipital part of brain.
 ECG: hyperkalemia with tall T, wide QRS complex and ST depres-
sion.
 Biopsy also confirms APSGN
 Serological evidence of post infectious etiology other than post
streptococcal, based on clinical suspicion: hepatitis B surface antigen,
anti-hepatitis B surface antibody, anti-hepatitis C antibody, myco-
plasma antibody, Epstein-Barr virus antibody.
 Cultures: Post-infectious glomerulonephritis: skin, tonsils
Shunt nephritis: Blood, cerebrospinal fluid, shunt tip (after removal)
Endocarditis nephritis: Blood
IgADIRGN: Blood, tissues

Indications of renal biopsy

 Delayed resolution (>8weeks)

 Oliguria, HTN and/ or azotemia persisting > 14 days
 Gross hematuria persisting > 8 wks.
 Nephrotic range proteinuria beyond 2 wks.
 Low C3 level beyond 12 wks.
 Persistent proteinuria beyond 6 months
 Persistent microscopic hematuria beyond 18 months
 Systemic features of vasculitis: Fever, rash, joint pain, heart disease,
ANA, anti-ds-DNA, ANCA, (to exclude vasculitis).
 Synpharyngitic presentation: possibility of C3 GP,IgAV
  RPGN (rapid profound AKI/ crescentic GN)
 Absence of serological evidence of streptococcal infection; normal
C3 levels (suspected chronic GN).
 Mixed nephritic nephrotic presentation.
 C3 glomerulopathy (exclusion of chronic GN)
 Recurrent nephritis
 Family history of GN

 Subclinical PSGN has mild to diffuse mild to diffuse mesangial

hypercellularity

Diagnostic criteria: At least 2-3 of the following

 Clinical:
 Edema-facial/peripheral
 Hematuria > 10 RBC/HPF or 2+ dip stick
 Hypertension
 Oliguria
 Laboratory findings:
 Urinalysis /dipstick:Hematuria
 Low C3
 ASO/ Anti DNA ase B/Streptozyme/NAPlr
 Biopsy suggestinve /exclusive
Causes of low complement-3
a. Acute poststreptococcal glomerulonephritis (APSGN).
b. Systemic lupus erythematosus (SLE).
c. C3 glomerulopathy (C3 GP)
d. Infective endocarditis (IE).
e. Shunt nephritis.
f. Cryoglobinemia.
g. Reflux nephropathy.
h. Hepatitis B virus (HBV)
i. Human immune deficiency virus (HIV)

Management

 Fluid and salt restriction.

 Use of loop diuretics to remove excess fluid and sodium is the mainstay
of treatment in acute glomerulonephritis.
 If F/O of fluid overload - loop diuretics, 1-5mg/kg up to 12 mg/kg
furosemide: mainstay of treatment. (maximum 240 mg single dose).
Slow push over 5-130 min (average 10 min) to avoid ototoxicity.
 Penicillin/other antibiotic – to prevent spread / eradicate GABHS,
McIssac criteria for Rx of sore throat, use antibiotic in case of inflamed
tonsil, adenoid, pharynx with exudate, cervical lymphadenitis and fever.
 HTN: Loop diuretics- 1-12mg/kg/day with close monitoring and
check BP before every infusion, anti-hypertensive.
 Antihypertensive medication should be started if blood pressure is
still elevated after intravenous furosemide has been given.
 Avoid ACI and ARB if serum K+ >5.5, GFR reduced by 1/3 rd,
avoid β blocker if LVF.
 Electrolyte disturbance (hyperkalemia):
 Restrict potassium containing food such as milk, tomato, fruits
and fruit juices.
 Intravenous frusemide, 2-5 mg/kg/dose
 If serum potassium remains at 6-7 mmol/L despite 2 doses of
frusemide, give oral resonium, 1g/kg, to a maximum of 30 g
  If potassium >7mmol/L accompanied by ECG changes
- IV 10 % calcium gluconate. 0.5ml/kg, upto a maximum of
20 ml given slowly over 15 minutes
- Nebulization with salbutamol: entry of K+ into cell (2.5 mg if
wt< 25 kg and 5 mg if wt> 25 kg.).
- IV salbutamol 4mg/kg
- IV insulin 1IU/5g dextrose anf dextrose 0.5g/kg
- Avoid sodium bicarbonate due to the risk of worsening of
hypertension from sodium load.
 Dialysis if acute kidney injury (AKI) or rapidly progressive
glomerulonephritis (RPGN). It is indicated in child with severe
oliguria and is not responding to frusemide with following criteria
- Severe hyperkalemia ≥7 mmol/L
- Severe acidosis
- Uncontrolled hypertension and severe fluid overload
- Pulmonary edema
 Encephalopathy:
 Symptomatic management, intravenous phenobarbitone for convulsion.
 Control of blood pressure.
 No long-term sequele
 Heart failure: Furosemide (1-12 mg/kg/day) + anti-hypertensive,
no role of digoxin. Generous frusemide use is scientific because
mechanism of hypertension and heart failure is due to sodium and
H2O retention by inflamed less permeable glomerulus.
 Sore throat, pneumonia, comorbidities need appropriate treatment.
 Treatment of RPGN
 Treatment of AKI- PD/HD + others (e.g., acidosis correction)

Prognosis
 Excellent:
 95-98%- complete recovery within 1-2 weeks.
  <1% immediate mortality. Fatality is due to heart failure with
pulmonary edema and hyperkalemia
 1% may proceed to CKD (chronic GN)., 8% in adult.
 1% may continue with mild hematuria, proteinuria, hyperten-
sion and upper side creatinine, may develop CKD in long run.
 Abnormal urinalysis can be found in 20% of children.
 Recurrence is rare because of life long immunity, smaller number
of nephritogenic strain
 Worst prognosis is with RPGN.

Poor prognostic factor

 Adult >60 yrs. with multiple comorbidities
 High creatinine at presentation
 Nephrotic presentation
 Extensive crescent on biopsy
 Early treatment of throat skin and other infection
 Scabies treatment: 5% permethrin and ivermectin
 Hand washing and personal hygiene
 Socioeconomic uplift
 Prophylactic penicillin or cotrimoxazole to high-risk group/contact
 Lifelong follow up for CKD, evolution/development of features of
APSGN differentials
 Clinically:
 Height
 Weight
 Blood pressure
 Anemia
 Investigation:
 Hb%
 Urine routine study- RBC, WBC/HPF, protein
 Serum creatinine
 New biomarker
Study has shown 3% HTN, <1% azotemia, 5.4% microhematuria, non-
nephrotic proteinuria in 7.2% children after follow up of 110 children for 15-18
yrs, they need follow up; may be lifelong, which may show differential like
C3GP, IgAV, chronic GN
Causes of recurrent gross hematuria:
 IgA vasculitis nephritis(previous HSP)
 IgA Nephropathy (Berger’s Disease)
 Alport syndrome
 Idiopathic hypercalciuria
 Thin basement membrane disease
 Cystic renal diseases
 Recurrent UTI
 Stone disease
 Obstructive uropathy
 Coagulopathy
 Wilm’s tumour

Infective endocarditis
 10% of PIGN can be due to infective endocarditis (IE).
 Renal involvement is found in 25-50 % of infective endocarditis;
mostly asymptomatic
 Focal embolic and non-suppurative GN common; can have infarct.
 Interstitial nephritis by antibiotic is possible.
 Native valve endocarditis rate is 1.7 -6.2/ 100000 person years in
USA and Europe. In adolescent young rheumatic valvular disease
has decreased.
 Endocarditis related to prosthetic valves, implantable devices and
drug abuse has increased. MRSA is also increasing.
 Bacterial endocarditis is 20-60 times more common in HD patient
with 50% mortality risk.
 Congenital heart disease and cardiac surgery are also risk factor
with current 4% mortality rate.

Pathogens
 Staphylococcus aureus more than 50%
 Staphylococcus epidermidis
 Streptococcus viridans and pyogens
  Enterococcus fecalis
 E. coli, Proteus
 Candida
 Mitral valvular calcification is commonly associated in IE.

Clinical features
 Microscopic hematuria and proteinuria for weeks to months is common
 Renal failure in one third of patient carries poor prognosis
 Crescentic GN and antibiotic associated acute interstitial nephritis
are possible
 Nephrotic syndrome is uncommon.
 Fever, leukocytosis, raised ESR
 Lack of classic symptom is responsible for 38% of autopsy diagnosis
of infective endocarditis
 Vegetation >20 mm age less than one year, presence of heart
failure and staph aureus are diagnostic
 Stroke by embolization can occur in 6% of children
 Large systemic embolization is caused by fungus or Haemophilus.
 Acute GN

Investigation
 Low C3 C4
 High rheumatoid factor
 Cryoglobulinemia
 Rarely ANCA antibody
D/D: GPA

Histology
1. Mesangial proliferative GN
2. MPGN pattern
D/D- HCV viral nephropathy
-Lupus nephritis
IF: deposit of IgG, IgM, IgA
EM: electron dense deposit in sub endothelial and sub epithelium
Histological changes are reversible with treatment.
Treatment
 Appropriate antibiotic for 4-6 wks.
 Crescentic GN - pulse methylprednisolone and plasmapheresis

Shunt Nephritis
 Incidence of shunt nephritis is 6%
 0.7-2% of infected AV shunt can presented with nephritis

Organism are
 Staphylococcus epidermidis
 Less often Staph aureus
 Pseudomonas
 Diphtheroid
 Propionibacterium

Clinical Features
 Haematuria, proteinuria, hypertension, nephrotic syndrome.
 Fever, anemia
 Rash
 Hepatosplenomegaly
 Features of raised intracranial pressure

Investigation:
 Low C3, C4, Hb
 Elevated ESR, cryoglobulin
 Rheumatoid factor titre
 Serum anti P ANCA titre

Treatment
 Intravenous antibiotic
 Shunt removal within a few weeks’ replacement of shunt
 Haemodialysis if ESRD
 No PD because of chance of meningitis
 ESRD if shunt removal is delayed
Other post infectious GN
 Osteomyelitis and intra-abdominal abscess may cause glomeru-
lonephritis, urine analysis abnormalities and nephrotic syndrome.
 Pneumonia caused by pneumococcus, mycoplasma pneumoniae
can cause immune complex induced glomerulonephritis, haematuria
and non-nephrotic proteinuria.
 Neuraminidase (Thomsen Friedreich (T) antigen) producing pneumo-
coccus may cause haemolytic uremic syndrome .
 Histology
 Diffuse proliferative GN
 Crescent common
 Membranoproliferative GN and some C3 deposition only,
rarely Ig.
 - Treatment of infection early and effectively.
 Fluid, Electrolytes and
Acid-base Disorder 09
Chapter

A. Fluid
The goals of intravenous (IV) fluid therapy are to prevent:
a. Dehydration.
b. Deficiencies of sodium and potassium.
c. Ketoacidosis.
d. Protein degradation.
2. There is no “one-size-fits-all” approach to IV fluid therapy, as the prescription
needs to be individualized to take into account the following:
a. Medical condition of the child.
b. Initial fluid, electrolyte and acid-base status.
c. Therapeutic goal.
d. Changes in the fluid, electrolyte and acid-base status with ongoing
IV fluid therapy and losses

Fluid Requirements for Children with Normal Hydration:

Daily maintenance fluid requirements via IV route:
1. Association between metabolic rate and fluid requirement:
a. Fluid maintenance volume is the volume of daily fluid intake, which
replaces the insensible losses (from skin, lungs and stools) and
the fluid required to excrete excess solute load (urea, creatinine,
electrolytes) in a child with normal kidneys.
b. In a child with average normal kidney response: 1 ml of water is
required for each kilocalorie consumed:
2. Calorie requirements:

3. Maintenance fluid requirements for a clinically well child with normal

hydration but no oral intake (e.g., prior to elective surgery):
 IL-WO= 30 ml/100 ml or 400 ml/m2
 1 ml of water is required for each kilocalorie consumed.
a. Calculated using Holliday–Segar method, which estimates caloric
expenditure from weight:

*This method may not be useful for; i) Babies who are < 28 days old. ii)
Calculating oral maintenance fluid requirements. iii) Patients who are
overweight.
4. Fluid requirement of an overweight patient is based on age and ideal body
weight (IBW) (kg):
a. Weight for 50% percentile for the patient’s age OR
b. Formula to get the IBW (in adolescent and adults)
i. Male: 50 + 2.3*(height in cm/2.5 – 60)
ii. Female: 45.5 + 2.3*(height in cm/2.5 – 60)5.
5. Maintenance fluid requirements for term neonates (< 28 days old):
5 (a) Maintenance fluid of well children (for normal hydration) < 40 kg:
0.45% saline with 5% dextrose, > 40 kg: 0.9% saline with 5% dextrose
6. Adjustment of maintenance fluid requirements may be needed in the
following:
a. Factors affecting insensible water loss:

b. Maintenance fluid requirements may be reduced to 50–80% in

inappropriate anti-diuretic hormone (ADH) secretion:
i. Post-surgery.
ii. Stress, pain, nausea or vomiting.
iii. Central nervous system disease.
iv. Liver disease.
v. Nephrotic syndrome.
 vi. Pulmonary disease.
vii. Hypothyroidism.
viii. Hypoadrenalism.
ix. Medications, e.g. carbamazepine, cyclophosphamide, vincristine,
selective serotonin reuptake inhibitors.
c. Underlying medical conditions with specific fluid requirements, e.g.,
kidney failure and cardiac failure

Types of solutions for IV maintenance fluids:

a. Hypotonic fluid should be used cautiously as increasing reports of
iatrogenic hyponatremia with catastrophic neurological outcomes
seen in hospitalized children receiving hypotonic maintenance
fluid therapy.
b. Cause of hyponatremia is due to a combination of a positive
balance of electrolyte free water (from the administration of
hypotonic fluid) and the impaired ability in sick patients to excrete
hypotonic urine secondary to ADH secretion.
c. Data supporting isotonic 0.9% saline solution as maintenance fluid
therapy include several meta-analyses based on small clinical
trials.
d. American Academy of Pediatrics (AAP) recommends that patients
from 28 days to 18 years of age requiring maintenance IV fluids
should receive isotonic solutions, which significantly decrease the
risk of developing hyponatremia.
 e. NICE 2015 guidelines recommend the initial use of isotonic crystalloids
that contain sodium in the range of 131–154 mmol/L as maintenance
fluid.
f. Physiologically, IV fluids according to their tonicity, redistribute mainly
to the interstitial fluid (isotonic fluids) or the interstitial and intracellular
fluid compartments (hypotonic fluids).
g. Isotonic fluids are typically employed in fluid resuscitation to correct an
acute intravascular fluid deficit. Administration of hypotonic fluids
generates the necessary osmotic driving force needed to allow the
movement of water from the extracellular to intracellular compartment,
hydrating both compartments, which is the goal of maintenance fluid
therapy in hemodynamically stable fasting children.
h. There is increasing evidence that the administration of Cl-rich IV
fluids (e.g., 0.9% saline that contains Cl exceeding that of plasma
by approximately 60%) is associated with:
i. Increased risk of mortality.
ii. Direct effect on intrarenal perfusion, vasoconstriction, and glomerular
filtration.
iii. Impaired coagulation (Cl-rich resuscitation fluid).
iv. Risk of fluid overload as compared to a balanced crystalloid
solution (e.g., PlasmaLyte with a Cl concentration closer to plasma
Cl concentration).
v. Hypertension.
Note: Children with impaired kidney functions are particularly at risk of the
above sequelae due to the reduced ability to excrete excess Cl. 0.9% saline
solution delivers Na and Cl loads 2x more than a 0.45% saline solution ml
for ml, which can potentially result in Na and Cl overload in children.

Choice of maintenance fluids:

a. Children < 40 kg: Use 0.45% saline solution (hypotonic solution) as
an initial maintenance fluid therapy for clinically well children and
adjusted in response to monitoring during intravenous fluid therapy.
b. Children ≥40 kg: Use 0.9% saline solution as 0.45% saline delivers
a Na load of < 4 mmol/kg/day, except in children who cannot
tolerate Na or Cl overload.
c. Recommended fluid to be infused as maintenance therapy for
clinically well children with normal hydration is: Children <40 kg:
0.45% saline with 5% dextrose. Children ≥40 kg: 0.9% saline with
5% dextrose. Add 1–2 mmol/kg/day of KCl (if there is no hyperkalemia
or kidney impairment).
 d. Do NOT use 0.45% saline with 5% dextrose solution in the following
situations: i. Serum Na is low (<130 mmol/L). ii. Initial treatment of
acute neurological conditions, e.g., meningitis and head injury. iii.
Conditions associated with syndrome of inappropriate anti-diuretic
hormone secretion (SIADH). iv. Volume resuscitation. Fluid restriction
in SIADH is 20-50%
e. Neonates:
i. For term neonates who are ≤ 7 days old, 0.45% saline with 5%
dextrose solution can provide excessive Na and inadequate
glucose. Consider a combination drip consisting of dextrose and
an added 20% sodium chloride (NaCl) to provide 4 mmol/kg/day
of Na and a glucose delivery rate of 4–6 mg/kg/min.
ii. For term neonates ≥8 days old, 0.45% saline with 5 to 10%
dextrose solution can be used safely.

Daily maintenance fluid requirements via ORAL route:

Due to the low caloric density of milk (67 kcal/ml) and significant water
loss in feces from oral feeding, the recommended oral maintenance fluid
volume is higher than the intravenous requirement.
Types of fluids:
a. Age ≤ 6 months old: Mainly milk.
b. Age > 6 months old: Water, milk and other fluids (once solid feeds
are established).

Fluid Requirements for Children with Dehydration:

The fluid requirements for a dehydrated child should include maintenance
requirements, deficit and ongoing loss.

Initial resuscitation (in established or impending shock):

1. Initial resuscitation should be: Fluid bolus of 20 ml/kg of 0.9% saline,
Ringer’s lactate, or PlasmaLyte solution.
2. In hypotensive patients: Give over 10 minutes. ·
3. If compensated shock: Give over 20–30 minutes.
*Note: Patients should not have signs of fluid overload.
4. Limit crystalloid fluid boluses in specific pre-existing conditions (e.g.,
cardiac or kidney disease), diabetic ketoacidosis, or trauma. In
trauma, give blood products early (bolus 10 ml/kg), preferentially over
crystalloids.
5. The child should be reassessed (heart rate, perfusion, blood pressure,
urine output) immediately after the fluid bolus, and additional fluid
bolus may be needed.
*Seek expert advice early (e.g., from intensivists) if >40–60 ml/kg of IV
bolus fluids are needed and/or inotropes are required

Maintenance volume requirement:

 Most children will tolerate standard fluid requirements as recommended
by the Holliday–Segar method mentioned above.
 Some acutely ill children with increased ADH secretion may benefit
from their maintenance fluid requirement being restricted to 50–80%
of the normal recommended volume.

Deficit volume replacement:

 Fluid deficit in ml can be calculated following an estimation of the
degree of dehydration expressed as a percentage of body weight.
Volume of fluid deficit (ml) = % dehydration/100 × weight (kg) ×
1000
 Recommended fluid to replace volume deficit: For patients < 40 kg
and without hyponatremia: 0.45% saline with 5% dextrose. For
patients ≥ 40 kg: 0.9% saline with 5% dextrose

Rate of replacement of fluid deficit depends on the child’s illness:

 Replacement may be rapid in most cases of gastroenteritis. Give
the first half of the total volume (fluid deficit + maintenance – initial
resuscitation volume) over the first 8 hours, followed by half of the
total volume over the next 16 hours.
 Replacement has to be slower in diabetic ketoacidosis and meningitis.
Replace the total volume over 48 hours.

Ongoing losses:
 Ongoing losses (e.g., from diarrhea, nasogastric suction, and drains)
should be measured and replaced regularly if the above combined
fluid deficit/maintenance approach fails to correct the dehydration.
  Replacement may be based on each previous hour or 4-hour
period, depending on the situation.
 Type of fluid used to replace ongoing losses depends on the
electrolyte composition of the fluid being lost. For example, nasogastric
suction losses should be replaced with IV 0.45% saline with KCl 10
mmol added to each 500 ml of 0.45% saline

Rehydration of Children with Severe Acute Malnutrition

 Severe acute malnutrition (SAM) is defined as a mid-upper arm
circumference < 11.5 cm or weight-for-height Z-score <–3.
 Rehydration of dehydrated children with SAM should be done
orally rather than intravenously, when possible, to reduce the risk
of overhydration and heart failure.
 Rehydrate initially using standard WHO low-osmolality oral rehydration
salt (ORS) solution (glucose 125 mmol/L, Na 45 mmol/L, K 40 mmol/L,
Cl 70 mmol/L, osmolality 300 mmol/L).
I. Give 5 ml/kg every 30 minutes for the first 2 hours.
II. If the child is still dehydrated, give F-75 (starter formula with 75
kcal and 0.9 g protein per 100 ml) 5–10 ml/kg/hour every alternate
hour for a maximum of 10 hours.
 III. Assess frequently: Every 30 minutes for the first 2 hours and
hourly thereafter.
 If in shock, give IV resuscitation fluid at 15 ml/kg/hour using any of
the following:
I. Ringer’s lactate solution with 5% dextrose.
II. 5% dextrose + 0.45% saline solution with KCl 20 mmol/L.
III. Monitor every 5–10 minutes for signs of overhydration and
congestive heart failure. If signs develop, stop IV fluid therapy
immediately.
Monitor serum electrolytes at baseline and 6-hourly until the child is fully
hydrated

B. Electrolytes

Introduction
 Male: solid muscle- 50%; water- 50%
 Female: ↑fat and solid- 40%; water- 60%
 In fetus- ˃75% is total body water (TBW), at birth TBW ~75%, early
infancy >60%, and after 1 year- 60% up to puberty.
 Total body water: Male 60%, female 50% because of more fat
 Blood- 8% of total body weight

Two compartment of TBW (out of 60%)

 Extracellular fluid (ECF)- 20%, (15% interstitial, 5% plasma)
 Intracellular fluid (ICF)- 40%.

Sodium (Na+) –
 Normal range 135-145mmol/l
 It is the determinant of plasma osmolality.
 Minimum urine osmolality is 30-50 mOsm/L and maximum is 1200
mOsm/L
 Plasma osmolality contributed by Na+ is called tonicity.
 Osmolality: 2 x (Na+) + glucose / 18 + BUN / 2.8, osmolality is
maintained to normal range of 285-295 mOsm/kg
  Effective osmolality: 2 x (Na+) + glucose / 18
 Normal plasma: 93% water by volume, 7% protein, lipids etc.
 Decrease H2O in ECF leads ECF high Na+ which causes increase
plasma osmolality, thirst, high ADH binds to V2 receptor in collecting
duct causes increased cAMP leading to insertion of aquaporin 2 and
increase permeability leads increase H2O reabsorption in DCT.
Angiotensin II helps Na (with H2O) reabsorption and K+ excretion in
DCT, CT
 If hypernatremia persist > 24 hours leads brain generates an excess
of low molecular wt organic solvents such as sugar, alcohol, methylamines,
amino acids that help increase ICF; idiogenic osmoles, includes organic
solutes; inositol, taurine and glutamine which help to prevent dehydration of
brain cells but rapid correction of persistent increased Na+ can cause
significant brain edema and dehydration. Oncotic adaptation needs 2 days.
Hyponatraemia (Na+<135 mmol/l; Mild: 130-135mmol/L, Moderate:
125-130 mmol/L, Severe: < 125mmol/L))
 Sudden decreased sodium; cerebral edema
 Gradual reduced Na+; no edema but alternate adaptation and
inadaptation causes cellular dehydration that may cause central
pontine myelinolysis (CPM). So during correction of Na+, it should
not rise > 0.5 mEq/L (˃12 mEq/L/day), 8-10 mEq/L/day

Classification
 Pseudohyponatremia (normal osmolality)
 Redistributive hyponatremia (hyper-osmolar)
 Hypovolemic hyponatremia
 Euvolemic hyponatremia
 Hypervolemic hyponatremia

Causes
 Pseudohyponatremia
 Osmolality is low in pseudo, normal in true
 Direct potentiometry by blood gas analyzer is useful
 Calculated Na= Measured Na- Triglyceride (mg/dl) × 0.002
 Calculated Na= Measured Na- plasma protein- 8 (gm/dl) × 0.025
  Calculated Na= Measured Na+ 1.6 × glucose (mg/dl)-100/100
 Hyperlipidemia, hyperproteinemia: Spurious low levels are
trivial, increase TG by 500 mg/dl and protein by 4gm will
decrease Na by 1gm/L
 Hyperosmolality
 Hyperglycemia, iatrogenic (mannitol, sucrose, glycine)
 Hypovolemic hyponatremia: (Simultaneous equal loss of Na
and water)
 Extra-renal losses (Urine Na+< 20 mEq/L)
 Gastrointestinal (emesis, diarrhea), skin (sweating or burns),
third space losses; decease volume leads to increase ADH
causing retention of water (bowel obstruction, peritonitis, sepsis),
dilute ORS
 Renal loses (Urine Na+ ˃20 mEq/L; ± volume change irrespective
of volume status)
 Acute glomerulonephritis (AGN), acute kidney injury (AKI),
chronic kidney disease (CKD)- dilutional hyponatremia
 Diuretic – loop, thiazide
 Diuretic (polyuric) stage of acute kidney injury (AKI)- nephrotic
syndrome, post obstructive diuresis, diabetic ketoacidosis (DKA),
osmotic dieresis, polyuric phase of acute tubular necrosis (ATN)
 Mineralocorticoid deficiency/resistance: Low Na, high K+,
increase HCO3
 Pseudohypoaldosteronism (CAH, Addison)
 AR-Polycystic kidney disease, obstructive uropathy, UTI due
to tubular dysfunction
 Cerebral salt wasting (high Hct, Increase BUN, increase
creatinine, low volume, urinary urea and uric acid is high): CNS
insult causing hyper secretion of B-type natriuretic peptide
causing polyuria, hypovolemia, decrease ADH. Treatment is
normal saline, NaCl, fludrocortisone.
 Juvenile nephronophthisis, autosomal recessive polycystic kidney
disease (ARPKD), tubulointerstitial nephritis (TIN), renal tubular
acidosis (RTA-II)
Euvolemic hyponatremia (Urine Na+ ˃20 mEq/L)
 PEM: Na and urea are breakdown product of protein
 Syndrome of inappropriate anti diuretic hormone (SIADH): Central
(classic)
 Nephrogenic syndrome of inappropriate antidiuresis
 Water intoxication (increase water drinking, hypotonic fluid,
iatrogenic, dilute bottle feeding, swimming, child abuse, drowning,
tap water enema)
 Post surgery (increased ADH, decrease tonicity, intravenous fluid)
 Hypothyroidism
 Glucocorticoid deficiency
 Desmopressin acetate
 Antidepressant medication
 Psychogenic polydipsia
 Exercise-induced hyponatremia
 Diarrhea and diuretic are two common cause
Hypervolemic hyponatremia (Urine Na+< 10 mEq/L)
 Increase ADH causes retention of water, decrease Na (dilutional);
retention of Na, H20 (low urine Na, <30meq/L- renal mechanism to
compensate);
 Increase aldosterone causes small rise of Na
 Heart failure
 Cirrhosis
 Nephrotic syndrome
 Acute, chronic kidney injury, CKD
 Capillary leak caused by sepsis, dengue
 Hypoalbuminemia caused by gastrointestinal disease (protein- losing
enteropathy)

Syndrome of inappropriate anti diuretic hormone (SIADH)

 Absence of renal, cardiac, liver, adrenal, thyroid disorder, nephrotic
syndrome, diuretics intake and dehydration, clinical evaluation
 Occurs with central nervous system (CNS) infection, tumor, trauma,
pneumonia, severe acute asthma, bronchiolitis, sepsis and pediatric
intensive care unit (PICU) setting illnesses (increase ADH).
  Urine osmolality ˃ 100 mOsm/kg, serum osmolality ˂ 275 mOsm/kg,
serum sodium <135 mEq/L and urinary sodium ˃ 40 mEq/l. (The
Schwartz and Bartter clinical criterion), decrease BUN, Uric acid.
 Reversal of “sodium wasting” and correction of hyponatremia with
water restriction.
 Central classic nephrogenic (mutation in AVP receptor-2 gene)
 Cause of SIADH: Pneumonia, TB, Asthma, severe respiratory distress due to
any cause, mechanical ventilation, meningitis, encephalitis, brain abscess,
brain tumor, trauma, GBS, disseminated malignancy, post-pregnancy,
intranasal ADH, carbamazepine, vincristine, cyclophosphamide, amitriptyline.
 Investigation: Serum osmolality
 Treatment: Curtail the fluid by 25-30% upto 50%, frusemide, NaCl
Tablet, treatment of cause

Clinical manifestation of hyponatremia:

 Degree of symptoms depend on Na+ level and rate of decrease
 Symptoms tend to occur at serum sodium levels lower than 125 or
when a rapid decline in sodium level
 Patients can have mild symptoms at sodium concentrations of
110-115 mEq/L when Na+ level fall gradually.
 Clinical feature of etiological entity
Hyponatremic encephalopathy is a medical emergency, severe cases
with edema due to water inside cell creates idiogenic osmols (inositol,
taurine). Intracellular dehydration causes chronic demyelination syndrome.
Diagnosis: MRI of pontine and other area to see increase intensity.
Increase Na slowly; 10-12 mEq/L/day. These changes may cause dysarthria,
lethargy, spastic quadriparesis and pseudobulbar palsy.

Management:
 It is a dire emergency
 Correction: Day-1; 10 mmol/L, day-2; 8 mmol/L
 Na+ deficit = (130 - S.Na+) x 0.6 x kg, it is not recommended for rapid
correction, because of chance of central pontine myelinolysis, flash
pulmonary edema. Then treat with desmopressin if severe hypovolemic
hyponatremia.
  Maintain fluid 5% DNS; 1.25 to 1.5 times that normal maintenance
 Concentration of Na+
  In N/S: 154 mEq Na+ /L
  In 3% N/S: 513 mEq Na+ / L
 In urgency/ symptomatic: NaCl: 3% at 4-6 ml/kg over 10-15 minute,
if no improvement repeat.
 Stop if Na+> 125 mEq/L rest deficit correction over next 48 hour.

Hypovolemic hyponatremia
 Replacement of volume by isotonic saline (0.9% saline) to
establish euvolemia- 20 ml/kg over 20 minutes, repeat if needed
 Volume repletion removes stimulus for ADH and allow free water
diuresis
 Replacement of ongoing losses with appropriate fluid
 Reassess, repeat IV N/S
 Calculate 24 hr fluid need: maintenance + deficit + acute loss /
ongoing loss
 Subtract isotonic fluid already given in bolus
 Give remaining fluid over 24 hr using ½ NS + 20mmol /L KCL (if K+
is low)

Euvolemic hyponatremia
 Syndrome of inappropriate anti diuretic hormone (SIADH)
 Fluid restriction- mainstay of therapy
 Rx of underlying cause
 Furosemide: I/V
 Vasopressin receptor antagonist – conivaptan, tolvaptan
 Hypothyroidism, cortisol deficiency → specific hormone therapy

Hypervolemic hyponatremia
 Water and salt restriction
 Diuretics
 Vasopressin antagonist- tolvaptan
  Optimal treatment of underlying cause
 Normal saline(NS) : Albumin + diuretic
 Renal failure: dialysis
 Heart failure: diuretics I/V furosemide 2-4 mg/kg even 10 mg/kg

Hypernatremia
 Invariably hyperosmolality exists
 Na+> 145 mEq/L; true H2O deficit, increase H2O loss, more Na+
retained
 In increased Na+ (>150 mEq/L); → proportional H2O loss;
increase antidiuretic hormone (ADH) and increased thirst
 Hemorrhage (subdural, subarachnoid, ventricular)- water moves
out of cell; decreased brain volume; tearing of the veins. CSF
protein increased.
 Thrombosis in venous sinuses.
 >160 mEq/L: Neurological features may develop
 Hypernatremia always associated with ↑glucose and ↓ calcium.

Cause
Excessive sodium

 Improperly mixed formula, concentrated oral rehydration salt (ORS )

 Excess sodium bicarbonate
 Ingestion of sea water or sodium chloride (P/O or enema)
 Intentional salt poisoning, salt water (near drowning), Munchausen
by proxy
 Intravenous hypertonic saline
 Hyperaldosteronism
Water deficit: Dehydration more, less volume, Na is extracellular (97%),
only 3% intracellular
 Diabetes insipidus: Nephrogenic and central
 Increased insensible losses
 Premature infants, radiant warmers, phototherapy
  Inadequate intake: Ineffective breastfeeding, child neglect or abuse,
adipsia (lack of thirst)
 Poor access in infant, handicapped, critically ill

Water and sodium deficits

 Gastrointestinal losses: diarrhea, emesis/nasogastric suction, osmotic

cathartics (lactulose)
 Cutaneous Losses: burns, excessive sweating
 Renal losses: Osmotic diuretics (mannitol), diabetes mellitus, CKD
(dysplasia and obstructive uropathy), polyuric phase of acute tubular
necrosis, post obstructive diuresis.
 Essential increase in Na: rare, injury to hypothalamic posterior pituitary
axis. It is euvolemic, non-hypertensive but hyperdipsia due to reset
osmol sensor

Classification

A) Euvolemic (due to loss of free water)

Causes:
Diabetes Insipidus (DI), increase insensible loss
B) Hypovolemic (due to loss of free water and Na+, water deficit > Na+
deficit)
Causes:
 Diarrhea, vomiting
 Burn, fistula, diuretic
C) Hypervolemic
Gain of Na+ and free water, Na+ gain > water gain
Causes:
 Hypertonic saline
 Accidental salt ingestion
 Cushing syndrome
Clinical feature:
 FRIED
 Fever
 Restless
 Irritability
 Edema
 Decreased urine output, dry mouth
 Doughy/flushed skin
 Others
 Muscular twitching
 Hyperreflexia
 Spasticity
 Seizure, coma (brain hemorrhage)
 Thrombotic complication: stroke, dural sinus thrombosis, renal
vein thrombosis
 CNS symptoms parallel to the degree of raised Na. High Na moves
water out of the cell causing decrease volume in brain. Sub-
arachnoid and subdural hemorrhage as tearing of vessel.
 Dehydration feature may not be overt, brain edema features (late)
may develop but ECF may be maintained
 Hemorrhage, thrombosis, coagulopathy, hyperglycemia, hypocalcemia
may exist
 Most children are dehydrated, may be asymptomatic
 Malnutrition in chronic cases
 Features of etiology

Treatment
 Shock with dehydration: 10-20 ml/kg NS or 5% albumin over 20-30
min
 If oliguric dehydration 0.45% NS
 If euvolemic 0.23% NS (baby saline) with caution
 Calculate free water deficit = weight x 0.6 (1-145) x S. Na + level
  It is equivalent to 3-4 ml of water per kg of each 1 mEq of Na+ that
exceed current level of 145 mEq/L
 Rapid correction can cause central pontine/extra pontine myelinolysis so
reduce ˂10 mEq/L of Na+ day
 Correct underlying cause
 If no dehydration, typical fluid: 5% dextrose (5%DNS) + ½ NS
(with 20 mEq/L KCL unless contraindicated)
 Concomitant hypokalemia give- KCl
 If diarrhea: cholera saline and ORS
 Hypocalcemia found in 10%, so correct it.
 Serum Na > 180 mmol/L is an indication for dialysis.

Potassium (K+)

 Normal serum level: 3.5-5meq/L (˂1% of total body K+ in plasma),

serum K+ is 0.4meq/L higher than plasma
 Concentration gradient is maintained by Na+-K+ ATPase, 93%
intracellular
 Small change may have profound CVS/CNS impact.
 Factor affecting movement between extra cellular fluid (ECF) and
intra cellular fluid (ICF)
 Acidosis/alkalosis,
 Insulin
 Catecholamine
 B2 agonist
 Exercise: releases K+
 Hyperkalemia (raised K+ ˃ 5.5 mEq/l; Neonate > 6meq/L, Preterm
>7 mEq/L)

Types
 Mild: 5.5-6.5 mEq/L
 Moderate: 6.5-8 mEq/L
 Severe: > 8 mEq/L
Causes of hyperkalemia (mostly insufficient renal excretion)
 Spurious: high K+ (factitious)
In vein puncture
 Prolonged torniquet test
 Squeezing
 Jerking while transport can cause hemolysis
 Leukocytosis
 Thrombocytosis (for every 1 lac K+ increase by 0.15 mEq/L)
 Clinching of fist
 Delay in processing blood
 Cold storage
 Storage at high temperature
 Heparin
 Familial pseudohyperkalemia (K+ release from RBC due to
genetic abnormality)
 Transcellular shift
 Acidosis
 Type-I Diabetes mellitus(DM), diabetic ketoacidosis (DKA)
 Dehydration and increased osmolality
 Strenuous exercise
 Hyperkalemic periodic paralysis (autosomal dominant, mutated Na
channel, episodic cellular K+ release with paralysis)
 Malignant hypertension
 Digitalis intoxication
 B-blocker
 Tissue necrosis
 Pseudohypoaldosteronism type I: AD, defect in Na channel causing
low volume, decrease Na, high K+, high H+, low HCO3. Severe
failure to thrive, diarrhea, recurrent pneumonia, mitharia rebon like
rash begin in infancy may remit in adulthood.
 Increased intake/release from damage cell
 Transfusion of old blood
 Rhabdomyolysis, TLS
  Severe exercise
 GI bleeding
 Hematoma

Low excretion:
 Acute kidney injury (AKI ), premature
 Chronic kidney disease (CKD)
 Type IV renal tubular acidosis (RTA)
 Lupus nephritis
 Calcineurin inhibitors (CNI), ACEi, ARB, NSAID, trimethoprim,
K+ sparing diuretics, COX-2 inhibitor, heparin
 Chronic TIN
 Aldosterone deficiency
 Primary- Addison’s disease, congenital adrenal hyperplasia
(CAH)
 Secondary
 Gordon syndrome
 Pseudohypoaldosteronism type II: AD, WNKI 4 mutation; Increase
volume, hypertension, hyperkalemia, hyperchloremia, acidosis.
Treatment with thiazide
 Aldosterone resistance
 Obstructive uropathy, Bartter syndrome
 Renal transplant
 K+ sparing diuretics
 Very low birth weight(VLBW)

Clinical features:
 Acute: Neuromuscular, cardiac
 Chronic; Asymptomatic; better tolerated
 Neuromuscular: Muscle weakness, fatigue, paresthesia, low bowel
syndrome, rhabdomyolysis, paralysis, skeletal muscle, trunk, extremities,
respiratory muscles and urinary retention
 Cardiac: SVT, VT, heart block
 Muscle cramp
  Drowsiness
 Low BP
 Arrythmia/cardiac arrest: in digitalis receiving underlying cardiac
disease
 Oliguria, diarrhea

Investigation:
 Serum potassium
 ECG
 Aldosterone, renin
 Urine spot/timed K+:Creatinine ratio
 Underlying cause-
 CBC, uric acid
 Creatinine phosphokinase (CPK), Ca+- rhabdomyolysis, etc.
ECG changes: Normal in spurious hyperkalemia
K (mEq/L) ECG findings
5.5-6.5 Tall peaked T wave, prolonged PR interval
6.5-8 Increased PR interval, P-flattening, QRS- progressive
widening, ST elevation
˃8 QRS merge with T forming sine wave, VF, asystole

Figure 9.1: ECG changes in hyperkalemia

Treatment:
 Stop K+ containing foods
 Calcium gluconate- 1ml/kg (not over 10 ml) over 10 minutes- to
antagonist cardiotoxic effect of K +
 Insulin- 0.1 U/kg/hr + glucose 0.5 gm/kg in 5%DA (2 ml/kg of 25%
glucose) over 30 minutes, can be repeated in ½ to 1 hr – quick
entry of K+ into cell.
 NaHCO3 – 1-2 mEq/kg over 5-10 minutes, effective only if
underlying acidosis present
 Nebulized salbutamol: 5-10 mg- potentiates effect of insulin +
entry of K+ into cell
 IV salbutamol has no difference with nebulized salbutamol
 Na+- K+ exchange resin- 0.5 to 1 gm/kg- eliminate excess of K +
 Loop diuretic – if good renal function (Frusemide 1-2mg.kg)
 Dialysis- if renal failure/TLS: HD removes by 4 hour, PD 15-20%
as effective as HD, CRRT in critically ill children
 Treatment of underlying cause
 In chronic cases: Fludrocortisone (decreases aldosterone, volume)

Hypokalemia (↓ K+: < 3.5 mEq/L)

 Mild: 3.0-3.5 mEq/L,
 Moderate to severe: ˂3 mEq/L

Causes:

 Spurious- leukocytosis, leukemia

 Poor intake: PEM, anorexia
 Transcellular shift (redistribution): Refeeding syndrome, alkalosis,
insulin,  blocker, hypokalemic periodic paralysis (AD, rare disease-
acute cellular uptake of K+), thyrotoxic periodic paralysis (Asian
with hyperparathyroidism can have sudden shift of K+ into cell).
 Gastrointestinal (GIT) loss: Diarrhea, vomiting, laxative over use,
congenital chloridorrhea (chloride diarrhea)
 Skin loss- Burn, increase sweating, cystic fibrosis
  Renal loss- Diuretic phase of AKI/ATN, post obstructive diuresis,
renal tubular acidosis (RTA), diabetic ketoacidosis (DKA), diuretic,
protein energy malnutrition (PEM), excessive dialysis, Bartter and
Gitelman syndrome
 Low magnesium: Aminoglycoside, Cisplatin
 Adrenal – adenoma, congenital adrenal hyperplasia(CAH)

Clinical feature:
 Asymptomatic
 Acute: Neuromuscular, cardiac
 Chronic: Renal, glycosuria, decrease growth
 Weakness
 Lethargy
 Hypoactive gut (constipation at 2.5 mEq/L)
 Alkalosis: shallow respiration- respiratory paralysis (low k+ with
metabolic alkalosis: a. with low chloride: vomiting, NG suction, low
chloride formula, diuretic, b. with high chloride and normal BP:
Bartter syndrome, Gitelman syndrome, c. high chloride with high
BP: CAH [Adenoma], renovascular disease, Cushing syndrome,
Liddle syndrome, renal tumor)
 Confusion
 Cardiovascular system(CVS) : Increased digitalis toxicity, arrythmia-
thready pulse
 Muscle: weakness, cramps, lethargy, paralysis, ileus, retention
 Chronic hypokalemic nephropathy- polyuria, polydipsia due to
decrease urinary concentrating ability, failure to thrive
 Hypokalemia: causes increase renal NH4 production- worsens
hepatic encephalopathy
 Severe hypokalemia- kidney damage by interstitial nephritis and
renal cyst.
 Chronic hypokalemia- like RTA, Bartter syndrome- poor linear growth

ECG changes (Slow depolarization):

 ST depression
 Wide P wave
  Flat T wave
 Appearance of U wave
 QT prolongation
 Digitalis induced arrythmia- Supraventricular tachycardia (SVT),
ventricular tachycardia (VT), heart block, VF and torsades de
pointes, cardiac arrest

Investigation:
Spurious exclusion by ECG, spot urinary K+, Spot urine K+/Cr ratio, Fe
K+ (fractional excretion of K+)

Treatment:
 Deficit: K+ required. = 0.6 x weight (kg) x (4 - measured level)
 Preferred- Per oral safe (3-4 mmol/kg/day; starting dose 1-2m Eq/kg/day;
maximum 60 mEq/kg/day) - potassium carbonate, acetate, citrate- 2-4
mEq/kg/day max. Span K+ tablet: 600mg (K=8 mmol/kg), Syp. KCL
(potchlor, Electro K)
 Intravenous- only symptomatic + ECG changes, paralytic ileus
 KCL- 0.5-1 ml with N/S given over 1 hr (max 40 mEq)
 Maximum infusion rate is 0.2 mmol/kg/hr to 0.4 mmol/kg/hr
 In diabetic ketoacidosis (DKA)- acidosis- redistribution occur, so in
correction of decrease K+ ; may have rebound raised K+
 Acidosis with hypokalemia: K+ acetate citrate
 With hypophosphatemia: K+ phosphate
 Serum K+
 > 3 mmol- KCl- 1 ml in 100 ml N/S,
 2-3 mmol- KCl- 1.5 ml in 100 ml N/S
 < 2 mmol- KCl- 2 ml in 100 ml N/S
 K+= [3-measured K+× wt (kg) × 0.04]
 Never give fast IV and concentration of K+ in IV fluid should not
exceed 60 mEq/L in peripheral vein and 80 mEq/L in central vein
 Monitor by ECG and serum K+ level
 Concomitant hypomagnesemia should be corrected as it causes
hypokalemia
  Treat underlying cause
 Food: Beans, citrous food, coconut, potato
 Should not be use with bicarbonate which may aggravate redistribution
and low K+
 Hypokalemia should be corrected prior to acidosis correction.

Figure 9.2: A showing T wave inversion and prominent U waves in

hypokalaemia

Figure 9.3: B showing long QU interval in hypokalaemia

Calcium
 Function of Ca:
1. Stabilization of cell membrane.
2. Signaling e.g., muscle contraction
3. Neurotransmitter and hormone (PTH) release
4. Co factor in clotting
5. Stabilization of skeletal and dental structure
  Calcium (Ca) exists in three forms in plasma:
1) Calcium bound to protein (40 %)
2) Ionized calcium (48 %)
3) Complexed with anions like phosphate, citrate, and bicarbonate
(12 %).
 Normal value: 8.5-10.5 mg/dl
 Bone, intestine, and kidney are key organs involved in Ca homeostasis
and is regulated principally by PTH and 1, 25 (OH) 2 D and to a lesser
extent by calcitonin.

Hypocalcemia
Definition:
 Preterm newborn – serum Ca < 7 mg/dl (1.75 mmol/l) or ionized Ca
< 1 mmol/l
 Term newborn – serum Ca < 8 mg/dl (2 mmol/l) or ionized Ca < 1.1
mmol/l
 Children – serum Ca < 8.5 mg/dl (2.12 mmol/l) or ionized Ca < 50
% of serum Ca

Causes:
 Vitamin D deficiency or impaired metabolism: Nutritional, VDDR,
BMD of CKD, AKI, NS (Ca binding protein loss)
 Hypoparathyroidism: DiGeorge syndrome, CHARGE association,
PTH gene mutations, calcium sensing receptor (CASR) abnormality
– gain of function mutations or antibodies to the receptors, hypo-
magnesemia, neck surgery/post-parathyroidectomy
 Pseudohypoparathyroidism type IA, IB, II
 Redistribution of plasma Ca: Tumor lysis syndrome (TLS), hyper-
phosphatemia, hungry bone syndrome, acute pancreatitis.
 Infants of diabetic mother
 Prematurity
 Birth trauma
 Birth asphyxia
 Hypomagnesemia: Mg is cofactor for PTH secretion
  Activating mutation of CaSR (autosomal dominant)
 Poor calcium intake: Parenteral nutrition, presence of dietary calcium
chelators, malabsorption
 Drugs - furosemide, steroids, phenytoin, phenobarbitone, rifampicin,
NaHCO₃
 Massive blood transfusion
 Leukemia
 Albumin infusion
 Alkalosis

Clinical features of hypocalcemia

Acute
 Neuromuscular irritability: paresthesia of lips, extremities (fingers
and toes), tetany, laryngeal stridor, apnea in neonates, seizures
 Cardiac: Congestive cardiac failure, arrhythmias, ECG: prolonged
QT interval, heart block
 Latent Sign: Chvostek sign, Trousseau sign, peroneal sign, tetany
 Myopathy, psychosis
 Depression, dementia
 Hypotension, prolonged QT, heart block

Chronic
 Candidiasis, subcapsular cataracts, basal ganglia calcifications, extra-
pyramidal symptoms, enamel hypoplasia, papilledema
 Features of rickets
 Latent signs (signs of Chvostek and Trousseau)
 Ventricular arrhythmia, congestive heart failure.
  Dry skin, eczema
 Hair loss, brittle nail
 Cataract
 Enamel hypoplasia

Investigation
 Serum ionized calcium, phosphate, magnesium, albumin, alkaline
phosphatase, electrolytes, creatinine
 ABG, 25 OHD, iPTH, ECG, renal USG
 Urine analysis

Treatment
 Symptomatic hypocalcemia: 1–2 ml/kg/dose of 10 % calcium gluconate
IV diluted to twice the volume in dextrose under cardiac monitoring
for bradycardia and repeat every 6–8 h. Once the symptoms have
resolved, oral supplements can be initiated at 50–100 mg/kg/day
of elemental calcium in 3–4 divided doses. Extravasation can
cause severe skin injury.
 Treatment of underlying cause of hypocalcemia.

Hypercalcemia
 Serum calcium >12 mg/dl (>3 mmol/l), total corrected Ca > 2.6
mmol/L
 Severe hypercalcemia >15 mg/dl (3.75 mmol/l).

Causes:
 Increase parathormone (PTH):
 Primary - Adenoma, multiple endocrine neoplasia, calcium-sensing
receptor mutation (loss of function).
 Primary and tertiary hyperparathyroidism (e.g., chronic kidney disease)
 Excess vitamin D: Hypervitaminosis D, sarcoidosis, granulomatous
diseases (Wegener’s, Crohn’s disease), tuberculosis, lymphoma,
leprosy
 Factors releasing Ca from bone: Thyrotoxicosis, immobilization, SLE
  Drugs: Thiazides, lithium, calcium and vitamin D supplements, vitamin A
 Inherited Ca sensing receptor (CaSR) loss of function
 Idiopathic infantile hypercalciuria
 Others: Idiopathic infantile hypercalcemia, William’s syndrome, milk
alkali syndrome, Addison’s/Cushing’s disease
Clinical features:
 Gastrointestinal: nausea, vomiting, constipation, poor feeding
 Cardiac: Hypertension, arrhythmias, shortened QT interval
 Neurological: Hypotonia, poor activity, psychiatric disturbances, coma
 Renal: Polyuria, polydipsia, nephrocalcinosis, nephrolithiasis, distal
renal tubular acidosis, acute renal injury
 Ocular: Band keratopathy, conjunctival and palpebral calcification
 Others: weakness, anorexia, bone pain
Investigation:
 Serum ionized calcium, phosphate, alkaline phosphatase (ALP),
parathormone (PTH), 25 vit D
 Calcium × phosphate product
 Renal function test(RFT)
 USG of thyroid
 Calcium creatinine ratio
 Corrected calcium = Measured Ca (mmol/L) + 0.02 [40-albumin)
g/L)
OR

36-s albumin
Serum Ca +
40

 ECG :short QT interval, arrhythmia

Treatment

 The four main strategies in management:

1) Decrease intestinal calcium absorption
2) Increase urinary Ca excretion
 3) Decrease bone resorption
4) Remove excess Ca with the help of dialysis.
 Hydration
 Loop diuretics
 Hydrocortisone
 Bisphosphonates: Pamidronate. zoledronate, etidronate
 Calcitonin
 Dialysis
 Surgical subtotal parathyroidectomy.
Hypomagnesemia: Mg < 0.7 mmol/L

Causes:
1. Loss by kidney: ATN, TIN, diuretic, CNI, aminoglycoside
2. Decreased absorption in gut: PEM, diarrhea
3. Endocrine: IDM, hyperaldosteronism, hypoparathyroidism, hyper-
thyroidism
4. Hungry bone syndrome, hypercalcemia, hypophosphatemia, IUGR.
Hungry bone syndrome occurs following parathyroidectomy,
thyroidectomy and correction of severe metabolic acidosis.
5. Acute pancreatitis
6. PPI long use with diuretics
Hypercalciuric hypomagnesemia
Barter type 5 due to gene CaSR (AD) and type 3 due to CLCNKB (Ca, Na,
K wasting)

Hypocalciuric (Gitelman like) hypomagnesemia

 Gitelman
 Barter 4
 EAST syndrome (epilepsy, ataxia, sensorineural deafness and
tubulopathy + motor delay + Gitelman type dyselectrolytemia):
KCNJ10 (AR)
 HHH: HTN, increase cholesterol, decrease Mg, decrease Ca: MTT
(Mt) gene inheritance
 Kearns- Sayre syndrome: opthalmoplegia, retinopathy, cardiac
conduction defect, and ataxia: mitochondrial DNA defect.
 Clinical feature:
Asymptomatic until Mg< 0.5 mmol/L
Weakness, tremor, seizure, athetosis, chorea, apathy, delirium, coma
Positive Chvostek and Trousseau sign
ECG: ventricular arrhythmia (Torsade De Pointes), premature atrial and
ventricular complexes, atrial fibrillation, tachycardia
Moderate hypomagnesemia: QRS widening and peaked T wave
Hypokalemia because of common cause, hypocalcemia (Mg is cofactor
for PTH secretion)
Investigation: FeMg >4% increase renal loss

Treatment:
Acute 0.1- 0.2 mmol/kg if 10% MgSO4 (0.25- 0.5 ml/kg)
Chronic: 0.2 mmol/kg/day PO TDS

Hyperphosphatemia:
 Causes: a) Decreased renal excretion - CKD, AKI, nephrotic
syndrome
b) Increased production- Tumor lysis, rhabdomyolysis, acidosis
c)Endocrine- Thyrotoxicosis, glucocorticoid deficiency, acromegaly
 Clinical feature: Non specific
 Symptom of hypocalcemia
 Treatment of causes

Hypophosphatemia:
Plasma PO4 < 1.2 mmol/L in infants and <0.8 mmol/L in adolescents
 Cause:
a) increased renal loss: vit D deficiency, hyperparathyroidism,
Fanconi syndrome, TIN, hypophosphatemic rickets, post renal
transplantation.
b) increased calcium uptake: refeeding syndrome, alkalosis, DKA
treatment
c) decrease absorption – vit D deficiency, malabsorption
d) corticosteroid excess
  C/F:
non specific
Decrease ATP: weakness, lethargy, paresthesia
Ricket

 Inv: serum phosphate

 Treatment: of cause
PO4 supplement
Vit D

C. Acid Base Disorder

Normal PH: 7.35-7.45
Acidemia: PH < 7.35; Acidosis- increase H+
Alkalosis: PH > 7.45; Alkalosis- decrease H+

*PH may be different during compensation, mixed disorder may exist

Table 9.14 Appropriate compensation during simple acid-base disorders

3 buffer systems in the body:
1) Blood buffer works within second
2) Respiratory: Minutes to hours
3) Kidney: Hours to days (usually 3-4days)

Metabolic acidosis
Causes:
 Diarrhea- HCO3 loss; lactic acidosis, decrease tissue perfusion
 Renal tubular acidosis (RTA) - HCO3 loss, H+ retention
 Diabetic keto acidosis (DKA)–Increase organic acid
 Fasting
 Acute glomerulonephritis (AGN)-Decrease excretion of H +
 Acute kidney injury (AKI) -decrease excretion of H+; decrease
bicarbonate, albumin, sulphate, urate, both causes mixed effect
and normal anion gap and metabolic acidosis
 Chronic kidney disease (CKD)–Decrease excretion of H +
 Addison
 Toxin- salicylate overdose, methylene, ethylene glycol
 Lactic acidosis due to tissue hypoxia, occurs in shock, severe
anemia, liver failure, disseminated malignancy, metformin, inborn
error of metabolism.
 Surgical intestinal damage
 Interstitial nephritis
 Ketoacidosis- by DM, starvation, alcoholic, acute glomerulonephritis,
chronic kidney disease
 Poisoning- salicylate, ethylene glycol
Anion gap:
 The anion gap is the difference between the measured cation
(Na+) and the measured anions (Cl− + bicarbonate). The anion
gap is also the difference between the unmeasured cations (K+,
magnesium, calcium) and the unmeasured anions (albumin,
phosphate, urate, sulfate)
 Blood anion gap: Na+ – (Cl- + HCO₃-)
  Normal: 14-18 mEq/L, range 12-20 mEq/l
 ˂12 mEq/l means absence of anion gap, ˃ 20 means presence of
anion gap (e.g., lactic acidosis, IEM)
 May results from unmeasured anion primarily phosphate,
sulphate, acidic protein and also by nonvolatile acid (lactic)
 Can be measured by difference between the unmeasured cations
(K+, Mg+ and Ca+) and anions (urate, albumin, sulphate and phosphate)
 Every mEq of reduced HCO3ˉ causes equal amount of chloride
increment hence anion gap remains same.
 Urinary anion gap [(urinary Na+ + K+)- urinary Cl)]: It is positive in
distal renal tubular acidosis (dRTA), it measures NH4.
 Normal urinary anion gap 30-35 mEq/l
 For hypoalbuminemia: For each 10 g/L reduction of serum albumin
decrease A:G by 2.5 mmol/L
Corrected AG = AG +2.5× [4.0- measured albumin g/dl]

Clinical Features:
 Acute acidosis: Rapid deep breathing (Kussmaul)
 Chronic acidosis: Nausea, vomiting, poor weight gain, weakness
 Abdominal pain
 Stupor, coma due to decrease brain metabolism
 Reduces cardiac contractility and cardiac output
 Arterial vasodilatation and hypotension
 Resistance to effect of catecholamine (at pH < 7.2)
 Decreased affinity of hemoglobin for oxygen and hence tissue
hypoxia
 Impaired leukocyte, lymphocyte function
 Stimulates interleukins and increases inflammation
 Hyperkalemia, decrease in ionized calcium levels
 Clinical features of underlying disease

Evaluation:
 Urinary anion gap: (urine Na+K)- (urine Cl-)
  It is caused by NH₄, it is not routinely measured, chloride concentration
of urine, provides an approximate estimation of NH₄ excretion.
 Extra renal loss of HCO₃ˉ: Increase NH4 excretion and increase
urinary anion gap
 HCO₃ loss from gut- decrease urinary anion gap

Treatment:
 Required when HCO3 < 18 mEq/l and pH <7.15
 Treatment:
 HCO3 deficit= 0.3 x wt (kg) x (desired- actual HCO3). It applies
for half correction
 IV correction if HCO3 is < 12 mmol/l
 In acidosis due to hypovolemia target correction is 15 mmol/l,
volume replacement will correct rest.
 In RTA correction upto 25 mmol/l is desirable.
 In DKA correct acidosis if pH <7.0 and target pH is 7.1
 7.5% NaHCO3 2-3 mEq/kg/dose diluted with twice volume of
IV fluid or 1:1 volume
 Oral base therapy is given to children with chronic metabolic
acidosis. Sodium bicarbonate tablets are available for older
children.
 Lactic acidosis- O2 inhalation
 Treatment of cause
 Complications of sodium bicarbonate therapy: hyperosmolality,
hypernatremia, hypokalemia, decrease in ionized calcium, intracerebral
acidosis, and shift of oxygen dissociation curve resulting in worsening
of tissue hypoxia and worsening of intracellular acidosis.
 Tris-Hydroxymethyl Aminomethane (THAM): THAM is a weak
alkali that reduces arterial [H+] without producing CO₂. It is an
alternative to bicarbonate therapy especially if acidosis is associated
with severe hypernatremia and high PCO₂. However, there are
few studies regarding its efficacy.
 Hemodialysis is another option for correcting a metabolic acidosis
 and it is an appropriate choice in patients with renal insufficiency,
especially if significant uremia or hyperkalemia is also present.
 Long term therapy for acidosis is needed for RTA, CKD, IEM
 Short term in AKI, AGN
 In diabetic ketoacidosis, insulin and IV fluid correct acidosis,
NaHCO₃ is not used because of hypervolemia. It is also true for
lactic acidosis.
 NaHCO3 tablet 600 mg contains 137 mg Na = 6 mmol Na + 6 mmol
HCO3
 Shohl’s solution = 1 mmol Na + 1 mmol citrate ( 3 mmol HCO 3) per
ml

Metabolic alkalosis

 Vomiting and diuretics are 2 common causes of metabolic

alkalosis
 Chloride responsive alkalosis respond to volume and chloride
replacement, it is usually due to loss of HCl from upper gastro-
intestinal tract, urine chloride ˂15 mEq/l, decreased volume so
replace volume.
 Chloride resistant alkalosis does not respond to volume replacement,
it is due to loss of H+ from distal nephron, urine Cl ˃ 20 mEq/l.
 Volume loss- ↑Na+/ HCO3 reabsorption from proximal convoluted
tubule (PCT), aldosterone secretion®Na+, ¯ H+, ¯K+® refractory to
therapy
 Phases of metabolic alkalosis: Initiation and maintenance are the
two phases of metabolic alkalosis. The alkalosis can persist after
the initiating process has resolved only if there are additional
factors maintaining it
 Initiation: Renal or extra renal losses of H+ (vomiting, nasogastric
suction, use of diuretics)
 Gain of HCO₃ (NaHCO₃ administration, citrate in transfused blood)
 Maintenance
 Chloride depletion: There is increased reabsorption of HCO₃ in
order to maintain electroneutrality. Decrease in luminal chloride
 decreases the activity of the intercalated cells and decreases
bicarbonate excretion.
 Potassium depletion: Bicarbonate reabsorption in both the proximal
and distal tubules is increased in the presence of potassium depletion.
 Volume contraction augments fluid reabsorption in the proximal
tubule increasing bicarbonate reabsorption and maintains
alkalosis.
 Reduced glomerular filtration rate (GFR) due to volume contraction
limits the filtration of HCO₃.

Causes
A. Chloride responsive (urine Cl- ˂ 15 mEq/l): Cl loss is greater than
Na, K loss with low volume.
 GIT
 Persistent vomiting
 Congenital hypertrophic pyloric stenosis
 Congenital primary/secondary hyperaldosteronism
 Barttar/Gitelman/Liddle syndrome; chloride losing diarrhoea
 NG suction
 Renal loss of H+
 Loop diuretic: Decrease volume, increase RAAS, high Na, low
K+ causes increase HCl excretion and alkalosis. Initially urinary
Cl increases (>20meq/L), later low (<15meq/L)
 Sweat loss in cystic fibrosis
 Post hypercapnia
 Intracellular shift of H+ - ¯ K+
B. Chloride resistance (urine Cl- ˃ 20 mEq/l)
 With hypertension- Adrenal adenoma, congenital adrenal hyperplasia
(CAH), renovascular hypertension, cushing syndrome
 With normal BP- Bartter syndrome, Gitelman syndrome, HCO-3
administration, hypoalbuminemia
 Emesis- Increase hydrochloric acid (HCL) loss (also water/volume
loss)- Increased HCO3 (citrate, blood transfusion) in blood (maintain
by renal tubule)
  Volume depletion
 Decreases GFR- Decrease HCO3 filtration
 Increase Na+ and HCO3 reabsorption on PCT by renin angiotensin
and aldosterone (RAAS)
 Increased aldosterone causes H+ and HCO3 reabsorption in
collecting tubule (CT).
 Hypokalemia occurs because of gastric loss and urinary loss by
aldosterone
 Aldosterone shifts K+ to cell
 Diuretics causes volume depletion which activates RAAS.
Diuretics causes increase delivery of Na into distal convoluted
tubule (DCT) and collecting tubule (CT) causing hypokalemia.
 Alkalemia compensated PCO2 by decreasing ventilatory drive
causing hypoxia
 Alkalemia increases Ca+ binding with albumin so decreases Ca+
causes tetany

Clinical Features
 Asymptomatic
 Symptomatic when ionized Ca+ is low: Neuromuscular irritability-
numbness, tingling, tetany, cardiac arrythmia
 High BP in raised mineralocorticoid hormone
 Volume depletion features like low pulse and low BP, capillary
filling ˃ 3 sec
 Hypokalemic features
 Features of hypoxia
 Arrythmia
 Mild metabolic alkalosis (HCO₃ > 28 mEq to < 36 mEq/l): asymp-
tomatic
 Moderate metabolic alkalosis (HCO₃ 36–42 mEq/l): paresthesia,
weakness, orthostatic hypotension, fatigue, muscle cramps,
lethargy, hyporeflexia, muscular irritability
 Severe metabolic alkalosis: (HCO₃ >45–50 mEq/l): arrhythmias,
tetany, seizures, delirium, stupor
  Complications: hypoventilation, hypoxemia, difficulty in weaning
from ventilator, increased digoxin toxicity, worsening of hepatic
encephalopathy
 Features of hypokalemia: muscle weakness, paralytic ileus, arrhythmias

Investigation:
 HCO3 / blood gas analysis
 Urinary Cl <10 meq/L- chronic volume depletion, increase (>20meq/L)
in diuretic induced
 Unexplained, significant raised HCO 3 – rule out compensatory
respiratory alkalosis

Treatment:
 Rx of underlying cause.
 Normal saline ± KCl for volume replacement
 Proton pump inhibitor (PPI)- decrease HCl secretion
 Replace potassium (KCl)
 Arginine hydrochloride- in chloride (Cl) resistant alkalosis
 Acetazolamide- decreases HCO3 reabsorption in proximal
convoluted tubule (PCT) and hence HCO3 loss
 Nasogastric replacement (NG) of NaCl
 Treatment of Bartter syndrome: oral K + and K+ sparing diuretics
 Gitelman: Magnesium per oral or intravenous.

Chloride-Responsive Metabolic Alkalosis

 Correct the hydration status with normal saline infusion @ 10

ml/kg over 10–30 min. May repeat the bolus, if indicated. Do not
use Ringer’s lactate.
 Associated hypokalemia should be corrected. For GI losses: decrease
frequency of nasogastric drainage, use antiemetics and drugs that
inhibit gastric acid secretion.
 In diuretic-induced metabolic alkalosis: stop or decrease the dose
of diuretics, use of K + -sparing diuretics and KCl supplementation.
Chloride-Resistant Metabolic Alkalosis

 Treat the underlying cause.

 Adrenal adenoma – surgical removal
 Primary hyperaldosteronism - NaCl restriction, KCl supplementation,
 Spironolactone
 Glucocorticoid remediable aldosteronism - low-dose dexamethasone
 Apparent mineralocorticoid excess – K+ supplements, K+-sparing
diuretics
 Bartter syndrome – K+ supplementation, K+ sparing diuretic,
indomethacin
 Gitelman’s syndrome – K+ supplementation, K+ sparing diuretics,
magnesium replacement
 Liddle’s syndrome – salt restriction, K+ supplementation, K+ -sparing
diuretics
 Triamterene, amiloride

Treatment of Refractory Metabolic Alkalosis

 Acetazolamide orally @ 5 mg/kg once daily and up to 8–30

mg/kg/day in 2–3 divided doses or intravenously @ 8–30
mg/kg/day in 2–3 divided doses; monitor serum K +.
 Life-threatening metabolic alkalosis (HCO₃ >50 mmol/l) with problems
in mechanical ventilation warrants the following options:
 Renal replacement therapy (hemodialysis or peritoneal dialysis) dialysate
fluid may be modified with reduced/absent base. Continuous form of renal
replacement therapy (e.g., CVVH) may be preferred.
 Direct titration with HCl infusion.
 The goal of HCl therapy is to decrease HCO₃ (bicarbonate) by 50
% aiming at reducing the pH <7.55 and HCO 3 < 40 mEq/l. Intravenous
0.1 M HCl (100 mEq H + per liter) via central vein is infused or
added to dextrose/amino acids/electrolyte solution. Pediatric dose
not firmly established. Rate of infusion should not exceed >0.2
mEq/kg/h.
 Limitations: volume of fluid required, hemolysis, venous thrombosis.
 Respiratory acidosis
Causes
 Pneumonia
 Pulmonary edema
 Acute severe asthma
 Massive pleural effusion
 Pneumo/hemothorax
 Respiratory muscle paralysis: GBS, OPC poisoning, myasthenis
gravis
 CNS disease
C/F: CNS
 Drowsiness
 Somnolence
 Irritability
 Restlessness
 Confusion
 Headache
Respiratory
 Compensated tachypnea
 Irregular breathing
 Cyanosis
Tachycardia
Mx: mechanical ventilation
Treatment of cause

Respiratory alkalosis
Causes: Anxiety
CNS
 Encephalopathy
 Infection
 CVA
 Fever, toxemia
Respiratory
  Pneumonia
  Asthma exacerbation
  Mild pulmonary edema
Hypoxia
ALF
Overventilation
C/F
  Increase in ventilation
  Respiratory muscle fatigue
Mx: Rx of cause
Weight Descriptor Definition
8 Seizure Recent onset, exclude metabolic, infectious or drug causes
8 Psychosis Altered ability to function in normal activity due to severe disturbance
in the perception of reality. Includes hallucinations, incoherence,
marked loose associations, impoverished thought content, marked
illogical thinking, or bizarre, disorganized, or catatonic behavior.
Exclude uremia and drug causes
8 Organic brain syndrome Altered mental function with impaired orientation, memory, or other
intellectual function, with rapid onset and fluctuating clinical features,
inability to sustain attention to the environment, plus at least 2 of the
following: Perceptual disturbances, incoherent speech, insomnia or
daytime drowsiness, or increased or decreased psychomotor activity.
Exclude metabolic, infectious, or drug causes
8 Visual disturbance Retinal changes of SLE: Includes cytoid bodies, retinal hemorrhages,
serous exudate or hemorrhages in the choroid, or optic neuritis.
Exclude hypertension, infection, or drug causes
8 Cranial nerve disorder New onset of sensory or motor neuropathy involving cranial nerves.
8 Lupus headache Severe, persistent headache, may be migrainous, but must be
nonresponsive to narcotic analgesia
8 Cerebrovascular accident New onset cerebrovascular accident(s). Exclude arteriosclerosis
8 Vasculitis Ulceration, gangrene, tender finger nodules, periungual infarction,
splinter hemorrhages, or biopsy or angiogram proof of vasculitis
4 Arthritis ≥2 joints with pain and signs of inflammation: Tenderness, swelling or
effusion
4 Myositis Proximal muscle aching/weakness, associated with elevated creatine
phosphokinase or aldolase or electromyogram changes or a biopsy
showing myositis
4 Urinary casts Heme-granular or red blood cell casts
4 Hematuria > 5 RBC/hpf. Exclude stones, infection or other causes
4 Proteinuria >0.5 g/24 hours
4 Pyuria > 5 WBC/hpf. Exclude infection
2 Rash Inflammatory type rash
2 Alopecia Abnormal, patchy, or diffuse loss of hair
2 Mucosal ulcers Oral or nasal ulcerations
2 Pleurisy Pleuritic chest pain with pleural rub or effusion, or pleural thickening
2 Pericarditis Pericardial pain with at least 1 of the following: Rub, effusion, or
electrocardiogram or echocardiogram confirmation
2 Low complement Decrease in CH50, C3, or C4 below the lower limit of normal for
testing laboratory
2 Increased DNA binding Increased DNA binding by Farr Assay above the normal range
1 Fever 1 >38°C. Exclude infectious causes
1 Thrombocytopenia Platelets <100 × 109/L. Exclude drug causes
1 Leukopenia WBC <3 × 109/L. Exclude drug causes
14
Chapter
Obstructive Uropathy

 Hindrance of urine flow.

 Early detection and intervention can prevent CKD.
 Genetic: gene has some rule in the development of ureter and kidney.
Karyotyping detection of trisomy 21, 18, 13 in intrauterine life can
be useful.
 UTD (upper urinary tract dilatation) incidence is 1-5.4% of all preg-
nancies of which 25% are persistent, rest are transient.
 Mild hydronephrosis detected in the second trimester is more common
in fetuses with Down’s syndrome compared with normal fetuses.
 90% of antenatal hydronephrosis are detected by 18 weeks gestation
and 95% by 22 weeks.
 50% of congenital hydronephrosis have no recognizable cause
(functional).
 Fetal urine flow is 4-6 times greater than neonatal period. This is
due to differences in renovascular resistances, glomerular filtration
rate and concentrating ability before and after birth. These differences
may contribute to ureteric dilatation in utero in absence of functionally
significant obstruction.
 PUJ (UPJ) obstruction is the most common cause of unilateral
hydronephrosis.
 PUV (posterior urethral valve) occurs in 1:5000 to 8000 male births,
2nd common cause of bilateral renal damage and hence CKD.
 Bilateral renal injury is responsible for CKD and ESRD in PUV
 CAKUT occurs in 0.1-0.6% of life birth and responsible for 50-60%
of CKD/ESRD, commonest cause of CKD.
 Renin angiotensin aldosterone system plays an important role in
renal development
 Genes affecting ureteral muscle development may play a rule in
congenital obstructive uropathy
 Tubulointerstial fibrosis and atrophy in obstructive uropathy results
from induction of cytokines in response to stretch stress injury
 Cell death, genes and signaling molecules are involved

Figure 14.1: Mechanism of renal damage

EGF – extracellular growth factor

ROS – reactive oxygen species
TGF β – transforming growth factor beta
 Etiology
 Congenital
 Trauma
 Calculi
 Inflammation
 Surgery
 External compression

Common types:
 Meatus: Stenosis, phimosis, preputial adhesion.
 Urethra: Posterior/anterior urethral valve, stricture, polyp, diverticulum
 Bladder: Bladder neck hypertrophy, neuropathic bladder.
 Ureterovesical junction obstruction: Congenital obstruction.
 Ureter: Stricture, calculi, vascular obstruction, ureterocele, primary
megaureter.
 Pelviureteric junction: Congenital pelviureteric junction obstruction,
kinks, bands, adhesion, calculi, aberrant vessels.
 Calyx: Infundibular stenosis, calculi, tuberculosis.

Pathology
 Obstruction causes dilatation of the upper part leads to hydro-
nephrosis that causes thinning of renal parenchyma, also repeated
infection which leads to scarring of renal parenchyma.
 Chronic obstruction causes chronic kidney disease (CKD), proteinuria,
hypertension
 Acute obstruction: Low glomerular filtration rate (GFR) e.g.; acute
kidney injury.
 “Brodel effect”: High inserting ureter, into dilated pelvis leading to
a marked obstruction and long stenotic ureteral segment

Clinical feature
Lower urinary tract symptoms:
 Asymptomatic
 Straining at urine
 Frequency
  Urgency
 Hesitancy
 Dribbling
 Full bladder
 Palpable kidney
 Sense of incomplete voiding
 Incontinence
 Poor stream
 No sense of full bladder (neuropathic bladder)
 Pelviureteric junction obstruction (PUJ Obs.) features
 Recurrent abdominal pain
 Mass
 Dietle’s crisis: mass resolve with passage of large amount of
urine with electrolyte abnormality
 Recurrent UTI
 Renal tubular acidosis (distal)
 Acute obstruction: Acute kidney injury
 Chronic untreated: chronic kidney disease (CKD)
 Features of etiology

Information of diagnostic investigations of obstructive uropathy

Ultrasound:
1. Unilateral/bilateral dilatation
2. Simplex/duplex system
3. APRPD (anteroposterior renal pelvic diameter)
4. Calyceal dilatation
5. Ureteric dilatator: proximal/distal
6. Bladder abnormalities.
MCUG:
1.Urethral anatomy
2. Valve
3. Bladder abnormalities
4. VUR
DMSA:
1. Differential renal function
2. Morphology
MAG-3:
1. Differential renal function
2. Drainage
3. Tubular function
MRU: Anatomy in detail

Treatment

 Early surgery of treatable causes

 Posterior urethral valve (PUV): Fulguration; cystoscopic resection
by pediatric resectoscope at 1st week of life at 5,7 and 12 o’clock
position.
 Vesico ureteric reflux (VUR), dilated ureter: Reimplantation, endoscopic
sclerotherapy
 Pelviureteric junction obstruction.: Pyeloplasty followed by DJ
stent
 Stone: PCNL (percutaneous nephrolithotripsy)/ESWL (extracorporeal
shockwave lithotripsy)
 Neurogenic bladder: Clean intermittent catheterization, diversion
procedure (Mitrofanoff, ileal conduit)
 Urethral stricture: Dilatation of urethra with probe.
 True phimosis: Circumcision
 Treatment and prophylaxis of urine infection
 Treatment of acute kidney injury.
 Treatment of chronic kidney disease (CKD) or end stage renal
disease (ESRD)

Favorable prognosis
 Normal USG at 12-24 week of gestation
 Creatinine <0.8 to 1mg/dL after bladder decompression, 75% maintain
normal function
 Visualization of corticomedullary junction
 Unfavorable prognosis in
 Oligohydramnios in utero
 Creatinine >1mg/dL after bladder decompression, all progress to ESRD
 Bilateral cortical cyst
 HDN at <24 weeks of intrauterine time
 Diurnal incontinence > 5yr old child, possible due to uninhibited
contraction of bladder
 Poor bladder compliance
 Atonia
 Dyssynergia
 Polyuria- due to distal RTA

Markers to predict ESRD in children

 Low GFR
 Microalbuminuria
 Urine protein creatinine ratio
 Low hemoglobin
 Increased serum phosphate
 Decreased serum albumin

Biomarkers of renal injury:

 Renal imaging
 Renal functional measurement
 Microscopic anatomy
 Markers of cellular function
 E.g., Proximal tubulopathy by B-2 macroglobulin and retinal binding
protein
 PNGAL and L-FABP levels increase 5 years before renal replacement
therapy
PNGAL: Plasma neutrophil gelatinase-associated lipocalin (NGAL)
L-FABP: liver-type fatty acid-binding protein (L-FABP)

Antenatal hydronephrosis
Antenatal hydronephrosis is defined as renal pelvic diameter ≥ 5 mm at
any gestational age and requires post-natal evaluation.
 Antenatal HDN is detected on USG in 1-5% of all pregnancies.
 Transient hydronephrosis is due to unilateral or bilateral narrowing of
PUJ that resolves in 3rd trimester, no further evaluation is needed.
 VUR can be bilateral in 60%, usually milder grades resolve
 Multicystic kidney disease is non communicating, non-functional
kidney tissue which undergo atrophy.
 Abdominal mass due to enlarged kidney: PUJ obstruction or multicystic
dysplastic kidneys
 Palpable bladder and/or poor stream and dribbling: posterior urethral
valve in a male infant
 Abnormalities in the spine and lower limb with patulous anus: neurogenic
bladder
 Single umbilical artery: congenital abnormalities of kidney and urinary
tract (CAKUT), particularly VUR
 Examination for other associated congenital anomalies: VACTERL
association, prune belly syndrome, branchial-renal-oto syndrome,
and retinal-renal syndrome.
 Deformities secondary to oligohydramnios: hip dislocation, talipes equinovarus
and potter facies, comprising a receding chin, low set ears, hyper-
telorism with epicanthic folds, and a compressed broad flat nose.
 Figure 14.2: SFU grading

 HDN mimickers
MCDK
Megaureter
Megacalycosis
Large renal cyst
Figure 15.3: An approach to postnatal management of antenatally detect-
ed hydronephrosis

Surgical treatment considered if

 Pelvic AP diameter >30 mm with calyceal dilatation
 <35% renal function on the affected side or decreasing function
with increasing pelvic diameter on USG
 Bilateral moderate to severe pelvic dilatation with raised serum
creatinine
 Obstruction of solitary kidney

Pelviureteric Junction Obstruction

 Commonest obstructive uropathy
 Incidence of 1 in 2000 children, with a male female ratio 3:1.
 Bilateral in 20-25% of cases, 70% on left side.
 Causes-
 Intrinsic due to adynamic segment
 Congenital
  Crossing vessel
 Arteriovenous malformation
 Ureteral fold, polyp
 Stone
 Association – VUR, VUJ obstruction, duplex system

Clinical feature:
 Abdominal pain (dull constant pain or severe spasmodic pain),
 Calculus
 Lump
 UTI, pyonephrosis
 Gross hematuria
 Dietl’s crisis- refers to abdominal pain and palpable renal mass
which resolves with passage of large amounts of urine
 Antenatal unilateral hydronephrosis (APD > 20 mm)
 Pelvis rupture

D/D
 Megacalycosis,
 Megaureter
 Unilateral congenital non obstructive dilatation (HDN)
 Renal cyst
 VUR

Diagnosis
 Ultrasonography of kidney and urinary bladder with post voidal
residual with mean cystic capacity, grading of hydronephrosis.
 Micturating cystourethrogram (MCUG) or voiding cysto-urethrogram
(VCUG): for lower tract urethra bladder and to exclude ipsilateral
VUR present in 10-15%.
 Dynamic renal scintigraphy (dynamic renogram with split renal function,
DTPA/MAG3) – MAG 3 is better.
 MRU/CTU: better for ureteric pathology
 MAG-3: better for kidney
  Urine routine microscopy (R/M/E), culture sensitivity and colony
count (C/S and C/C)
 Serum creatinine
 Biomarkers of uteropelvic/pelviureteric junction obstruction: In urine
and serum
 Monocyte chemotactic peptide (MCP-1)
 Macrophage inflammatory protein 1 (MIP-1a)
 Osteopontin (OPN)
 Neutrophil-gelatin associated lipocalin (NGAL)
 Cystatin C
 B2 –Microglobulin
 Heme oxygenase-1 (HO-1)
 KIM-1 (kidney injury molecule 1)
 TGF β (transforming growth factor beta)

Treatment of pelviureteric junction obstruction

 20% will need surgery, rest may resolve, may not need surgery.
 Anderson Hynes pyeloplasty followed by DJ stent
 APRPD > 40mm: Early pyeloplasty
 APRPD > 30 mm: pyeloplasty
 APRPD: > 20-30mm: 40% needs surgery, 35% resolve, 25%
remain static.
 Indications of surgery in PUJ obstruction:
 T ½ (elimination time) of diuretic renogram > 15-20 min.
 Differential renal function < 40% in subsequent scan
 Declining renal function >5%
 If function drop 10 % in second MAG3
 Progressive thinning of renal cortex
 Significant grade hydronephrosis, >20mm with marked
calyceal dilatation
 APD >30 mm
 Presence of hypertension, hematuria, stone, unilateral flank pain.
 Frequent pyelonephritis.
  F/U: Week, 1 and 6, then every 3 months in 1st year, every 6 months
in 2nd yr, then annually until 4 yr.
If dilatation is static in 1st yr: then 2nd MAG-3 at 1 yr to see maintained
function
 Nephrectomy if differential function <5-10%- no improvement,
source of HTN, infection.
 Other supportive care
 Affected kidney will always have low GFR

VUJ dysfunction:
 Any dilated ureter >7mm, without VUR and poor drainage on MAG3
 Ureteric dilatation improves spontaneously in 1/3rd, remain static
in further 1/3rd.
 Protocol of f/up is same as PUJ dysfunction.
 British association of Pediatric Urologist recommends intervention
if
 Distal ureter is > 10 mm and child has febrile UTI and pain.
 Differential function is < 40%
 Differential function drops by >10% on serial isotope scan
 Dilatation progresses to > 15 mm even asymptomatic
 Cystoscopy, ureteric stenting and dilatation is intervention of choice
 Ureteric reimplementation if stenting fails.
 Ureterovesical junction obstruction (VUJ obstruction)
(obstructive megaureter)

 30-40% bilateral, left >right

 Meyer-Wiegert rule: ectopic ureter is obstructed, dilated and drains
upper pole moiety of kidney which may be dysplastic. In 80% of
ectopic ureterocele is lateralized, can present as refluxing with obstructive
system.
 Surgical correction of VUJ obstruction needed in 40% because of
spontaneously resolution of 60%.
 Balloon dilatation and resection of narrow segment.
 High risk of recurrence and VUR

Posterior Urethral Valve

 It is persistent urethral membrane

 The second most common cause of childhood obstructive uropathy
 Incidence: 1:5000 to 8000 births, 16% of cases of CKD
 Valves are of three forms
 Exclusive in boy, anterior urethral valve may occur in girl.
Type-I: Commonest form, appear to radiate distally from the verumontanum
& merge into each other to form anterior commissure.
Type-II: Usually undetected because the valves spread proximally & do
not obstruct the flow of urine.
Type-III: Less common, consisting of a diaphragm with a central hole.

Clinical features of PUV

 Antenatal hydronephrosis
 LUT symptoms
 Bed wetting
 Proteinuria, HTN (reflux nephropathy)
 CKD/AKI
 The classical features on antenatal scanning include oligohydramnios,
bilateral hydronephrosis and hydroureter, a thick-walled bladder and a
dilate posterior urethra, renal dysplasia and pulmonary hypoplasia
  Tubular damage with dysfunction may cause hyponatremia acidosis
with hyperkalemia
 Potter facies
 Walnut like mass in suprapubic area, urinary ascites.
 Tubular damage may cause hyponatremia, hypokalemia and acidosis.
 Secondary VUJ obstruction develops because of bladder wall thickening.
Renal damage in posterior urethral valve is due to
 Bladder dysfunction
 Chronic VUR
 Persistent/recurrent obstruction
 Polyuria
 Hyperfiltration
 UTI
 Hypertension by RAAS activation.

Diagnosis
 Endoscopy: urethroscopy, cystoscopy
 MCU with RGU
 Urine/R/E C/S
 Creatinine and other biomarkers

Treatment of PUV

 Post urethral valve (PUV): With cold knife fulguration/ electro- fulguration
(cautery); cystoscopic resection at 5, 7 and 12 clock positions by pediatric
resectoscope at 1st week of life. Appropriately sized resectoscope for
term, pre-term, infant.
 Reflux (70% unilateral, 30% bilateral) bladder dysfunction, renal dysplasia
(valve bladder dysfunction) to be treated with IV antibiotic for urosepsis,
correction of acidosis, dehydration.
 Urosepsis/too sick child non availability of resectoscope and skill
hand should have cystostomy. Cystostomy is temporary, poor choice
 Percutaneous nephrostomy and high loop ureterostomy is temporary
 But ultimately fulguration should be done.
  Catheter may not enter into bladder
 Diversion (Mitrofanoff, ileal conduit)
 Intrauterine (2nd trimester) Rodeck vesicoamniotic shunt improves
patient survival, reduces CKD load, may be technically difficult can
have complication like preterm labor, premature rupture of
membrane, chorioamnionitis with fetal loss.
 Urine electrolyte predicting good Rodeck vesicoamniotic shunt
outcome are:
Urine Na < 10 mmol/L
Urine chloride < 90 mmol/L
Urine osmolarity < 210 mmol/L- Means normal fetal tubular
reabsorption of Na and Cl and ability to concentrate urine
 Circumcision reduces UTI by >80%.

Treatment of ESRD in PUV-

 30-50% patients show progressive deterioration of kidney function
(CKD) need RRT.
 Thirty percent develop ESRD, 20% ongoing renal impairment and
ultimately CKD, 50% grow out of the problem with good renal
function
 Bladder pressure determination by urodynamic study
 High bladder pressure needs correction by Mitrofanoff appendico-
vesicostomy, bladder augmentation and Ileal diversion
 Transplant if normal bladder pressure.
 Dialysis if high bladder pressure.

Vesicoureteric reflux (VUR)

 Retrograde flow of urine from the bladder to the ureter & kidney.
 Reflux occurs when the submucosal tunnel between the mucosa
and detrusor muscle is short or absent.
 1-2% of healthy children have primary VUR
 M:F upto 6 month 1:3, then 1:1.
 20-30% of children and 40-50% of neonates with UTI have VUR.
 20-40% with urine infection and vesicoureteric reflux develop renal
scarring, of which 5-10% progress to end stage renal disease (ESRD).
Renal scaring in VUR is called reflux nephropathy, hypertension, proteinuria
can be presentation.
 Gross vesicoureteric reflux during infancy is seen in boys and is
usually bilateral.
 In older children, girls have milder VUR.
 Reflux at birth described in 25% with neuropathic bladder, 50%
with PUV, 15% with multicystic dysplastic kidney.
 Types of VUR:
a) primary VUR – maturational abnormality of the ureterovescical
junction
b) secondary VUR – due to abnormally high voiding pressures as
a result of obstruction of lower urinary tract
 VUR Grading based on MCU
 Grade-I: Reflux into a nondilated ureter
 Grade-ii: Reflux into the upper collecting system without dilatation
 Grade-iii: Reflux into dilated ureter & blunting of calyceal fornices
 Grade-iv: Reflux into a grossly dilated ureter
 Grade v: Massive reflux with significant ureteral dilatation, tortuosity
& loss of the papillary impression.
 VUR is diagnosed by MCUG or contrast enhanced voiding ultrasonography
(CeVUS) done after resolution of bacteriuria/UTI.
Figure 14.4: Different grading of vesicoureteric reflux

Treatment
 Grades 1-2
 Antibiotics prophylaxis until 1 year old and restart antibiotic prophylaxis
if breakthrough febrile UTI.
 Grades 3-5: Antireflux surgery. It consists of reimplantation of
ureter into another site of bladder (neocystostomy) in oblique manner
with a bladder mucosal flap at its opening, so that urine does not
leak back while bladder contracts. Reported good success rate is
98%.
 Antibiotic prophylaxis until 5 years old, consider surgery if break-
through febrile UTI
 Beyond 5 years, prophylaxis continued if there is bowel bladder
dysfunction.
 Endoscopic correction of VUR by subureteric transurethral endoscopic
injection (STING) of dextranomer or hyaluronic acid copolymer
(Deflux) and its modification hydrodistension implantation technic
(HIT)
 Success rate in grade I 78%, grade II 72%, grade III 63%, grade
IV and V 51%. Overall success rate is 68%.
 Endoscopic submucosal injection of deflux in intramural segment
of ureter for grade IV and V is an alternative. Success rate for
correction is 83%
  Cure rates per ureter for grade I and II is 78%, grade III > 72%,
grade IV 63% and grade V 1%.
 Indication of continuous antibiotic prophylaxis
Age ≤ 2 years with dilating VUR (grade III-V), until at least 2 years
after a febrile UTI
Age > 2 years with dilating VUR (grade III-V) and febrile UTI,
until at least 2 years after a febrile UTI
Recurrent UTI and non-dilating VUR (grade I-II), until 2 years
after a febrile UTI

 Combined surgical and antibiotic treatment versus antibiotics alone

did not reduce the risk of febrile UTI for upto 2 years but caused 57%
reduction in febrile UTI by 5 years but didn’t result in reduced risk of
new or progressive kidney damage at any time point.
  Surgical correction of VUR has not shown to be superior to long
term antibiotic prophylaxis in preventing kidney scarring, cortical
thinning, or poor kidney growth.
 Long term follows up necessary for children with cortical scarring
or congenital dysplasia, mainly to prevent the development of VUR-
related sequelae such as hypertension, pregnancy complications, UTI
or chronic kidney disease.

D/D of loin mass

 Hydronephrosis
 Wilms tumor
 Perinephric abscess
 Teratoma
 Dermoid
 Hematoma
 Rhabdosarcoma
 Renal vein thrombosis.

Bladder Diverticulum
 Outpouching of bladder mucosa through bladder wall
 May be acquired or congenital
 Causes-
 Bladder outlet obstruction
 Neuropathic bladder
 Prune belly syndrome
 Ehlers Danlos syndrome
 Post-surgery
C/F: LUT symptom
UTI
Renal impairment
Treatment: Excision of diverticulum and ureter reimplantation
Ureterocele
 Dilation of terminal part of ureter
  Usually inside the bladder may be outside
 Ureterocele is bilateral in 10-15%, associated with duplex kidney
in 80-90% and ectopic ureter in 75%, majority need surgical
correction.
 May be single kidney/duplex kidney-duplication in 100% girls and
50% of boys with ureterocele.
 Duplicated one drains upper nonfunctional dysplastic moiety
 Obstruction and hydroureteronephrosis is possible
 Reflux is possible in opposite side
 Dx-Cobra head appearance in IVU, VCUG and USG are diagnostic

D/D
Ectopic ureter may displace bladder and may appear as ureterocele (pseudo
ureterocele)

Treatment
Endoscopic deroofing
Reimplantation of ureter in VUR
Excision and reimplantation of ureter if obstruct bladder outline
(laparoscopic, robotic, open)

Megaureter
 The ureteric diameter more than 8 mm
 Aperistaltic common
 Classification- 1. obstructed, 2 refluxing, 3. obstructed and refluxing,
4. neither obstructing or refluxing
 It is bilateral in 25%
 Opposite kidney is absent or dysplastic in 10-50%
 Figure 14.5: Megaureter classification

 Causes-
Spina bifida
Tethered spinal cord
Neurogenic bladder
Ureterocele
Ectopic ureter
Bladder diverticulum
Periureteral fibrosis
Tumor compression
Aberrant vessels
 C/F
1. Groin pain
2. Hematuria
3. UTI
 Dx
MAG-3
 DTPA
MCU
IVU
MRU/CTU better

Treatment
 Excision of obstructing lower segment of ureter and reimplantation.
HDN takes years to resolve.
 Nephroureterectomy if split renal function is less than 5-10%, severe
urosepsis, stone or increasing HDN.
Prune belly syndrome: 1:40000 male, cause of 1-2.6% of CKD
1. Deficiency of abdominal wall, undescended testis,
2. Oligohydramnios, pulmonary hypoplasia.
3. Massive dilatation of urinary tract (ureter, bladder, urethra) secondary
to dysplasia
4. VUR, patent urachus, urachal cyst
5. PUV, obstruction at PUJ and VUJ
6. Malrotation of gut and heart
7. Empty hypoplastic scrotum, invariably infertile.
8. Poor bladder contraction, significant PVR
9. Telepes equinovarus, congenital dislocation of hip
10. Wrinkles lax abdominal wall
Inv: MAG 3, MRU
Rx:
Vesicostomy and other diversions.
Abdominal wall reconstruction
30% reaches ESRD
24
Chapter
Appendix
 Blood Pressure Levels for Boys by Age and Height Percentile

BP Systolic BP (mmHg) Diastolic BP (mmHg)

Age Percentile Percentile of Height Percentile of Height
(Year) 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
1 50th 80 81 83 85 87 88 89 34 35 36 37 38 39 39
90th 94 95 97 99 100 102 103 49 50 51 52 53 53 54
95th 98 99 101 103 104 106 106 54 54 55 56 57 58 58
99th 105 106 108 110 112 113 114 61 62 63 64 65 66 66
2 50th 84 85 87 88 90 92 92 39 40 41 42 43 44 44
90th 97 99 100 102 104 105 106 54 55 56 57 58 58 59
95th 101 102 104 106 108 109 110 59 59 60 61 62 63 63
99th 109 110 111 113 115 117 117 66 67 68 69 70 71 71
3 50th 86 87 89 91 93 94 95 44 44 45 46 47 48 48
90th 100 101 103 105 107 108 109 59 59 60 61 62 63 63 9
5th 104 105 107 109 110 112 113 63 63 64 65 66 67 67
99th 111 112 114 116 118 119 120 71 71 72 73 74 75 75
4 50th 88 89 91 93 95 96 97 47 48 49 50 51 51 52
90th 102 103 105 107 109 110 111 62 63 64 65 66 66 67
95th 106 107 109 111 112 114 115 66 67 68 69 70 71 71
99th 113 114 116 118 120 121 122 74 75 76 77 78 78 79
5 50th 90 91 93 95 96 98 98 50 51 52 53 54 55 55
90th 104 105 106 108 110 111 112 65 66 67 68 69 69 70
95th 108 109 110 112 114 115 116 69 70 71 72 73 74 74
99th 115 116 118 120 121 123 123 77 78 79 80 81 81 82
6 50th 91 92 94 96 98 99 100 53 53 54 55 56 57 57
90th 105 106 108 110 111 113 113 68 68 69 70 71 72 72
95th 109 110 112 114 115 117 117 72 72 73 74 75 76 76
99th 116 117 119 121 123 124 125 80 80 81 82 83 84 84
7 50th 92 94 95 97 99 100 101 55 55 56 57 58 59 59
90th 106 107 109 111 113 114 115 70 70 71 72 73 74 74
95th 110 111 113 115 117 118 119 74 74 75 76 77 78 78
99th 117 118 120 122 124 125 126 82 82 83 84 85 86 86 8
8 50th 94 95 97 99 100 102 102 56 57 58 59 60 60 61
90th 107 109 110 112 114 115 116 71 72 72 73 74 75 76
95th 111 112 114 116 118 119 120 75 76 77 78 79 79 80
99th 119 120 122 123 125 127 127 83 84 85 86 87 87 88
9 50th 95 96 98 100 102 103 104 57 58 59 60 61 61 62
90th 109 110 112 114 115 117 118 72 73 74 75 76 76 77
95th 113 114 116 118 119 121 121 76 77 78 79 80 81 81
99th 120 121 123 125 127 128 129 84 85 86 87 88 88 89
10 50th 97 98 100 102 103 105 106 58 59 60 61 61 62 63
90th 111 112 114 115 117 119 119 73 73 74 75 76 77 78
95th 115 116 117 119 121 122 123 77 78 79 80 81 81 82
99th 122 123 125 127 128 130 130 85 86 86 88 88 89 90
 Blood Pressure Levels for Boys by Age and Height Percentile (cont’d)

BP Systolic BP (mmHg) Diastolic BP (mmHg)

Age Percentile Percentile of Height Percentile of Height
(Year) 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
11 50th 99 100 102 104 105 107 107 59 59 60 61 62 63 63
90th 113 114 115 117 119 120 121 74 74 75 76 77 78 78
95th 117 118 119 121 123 124 125 78 78 79 80 81 82 82
99th 124 125 127 129 130 132 132 86 86 87 88 89 90 90
12 50th 101 102 104 106 108 109 110 59 60 61 62 63 63 64
90th 115 116 118 120 121 123 123 74 75 75 76 77 78 79
95th 119 120 122 123 125 127 127 78 79 80 81 82 82 83
99th 126 127 129 131 133 134 135 86 87 88 89 90 90 91
13 50th 104 105 106 108 110 111 112 60 60 61 62 63 64 64
90th 117 118 120 122 124 125 126 75 75 76 77 78 79 79
95th 121 122 124 126 128 129 130 79 79 80 81 82 83 83
9th 128 130 131 133 135 136 137 87 87 88 89 90 91 91
14 50th 106 107 109 111 113 114 115 60 61 62 63 64 65 65
90th 120 121 123 125 126 128 128 75 76 77 78 79 79 80
95th 124 125 127 128 130 132 132 80 80 81 82 83 84 84
99th 131 132 134 136 138 139 140 87 88 89 90 91 92 92
15 50th 109 110 112 113 115 117 117 61 62 63 64 65 66 66
90th 122 124 125 127 129 130 131 76 77 78 79 80 80 81
95th 126 127 129 131 133 134 135 81 81 82 83 84 85 85
99th 134 135 136 138 140 142 142 88 89 90 91 92 93 93
16 50th 111 112 114 116 118 119 120 63 63 64 65 66 67 67
90th 125 126 128 130 131 133 134 78 78 79 80 81 82 82
95th 129 130 132 134 135 137 137 82 83 83 84 85 86 87
99th 136 137 139 141 143 144 145 90 90 91 92 93 94 94
17 50th 114 115 116 118 120 121 122 65 66 66 67 68 69 70
90th 127 128 130 132 134 135 136 80 80 81 82 83 84 84
95th 131 132 134 136 138 139 140 84 85 86 87 87 88 89
99th 139 140 141 143 145 146 147 92 93 93 94 95 96 97

BP, blood pressure

* The 90th percentile is 1.28 SD, 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD
over the mean.
For research purposes, the standard deviations in Appendix Table B–1 allow one to compute BP
Z-scores and percentiles for boys with height percentiles given in Table 3 (i.e., the 5th,10th, 25th,
50th, 75th, 90th, and 95th percentiles). These height percentiles must be converted to height
Z-scores given by (5% = -1.645; 10% = -1.28; 25% = -0.68; 50% = 0; 75% = 0.68; 90% = 1.28%;
95% = 1.645) and then computed according to the methodology in steps 2–4 described in
Appendix B. For children with height percentiles other than these, follow steps 1–4 as described
in Appendix B.
 Blood Pressure Levels for Girls by Age and Height Percentile (cont’d)

BP Systolic BP (mmHg) Diastolic BP (mmHg)

Age Percentile Percentile of Height Percentile of Height
(Year) 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
l 50th 83 84 85 86 88 89 90 38 39 39 40 41 41 42
90th 97 97 98 100 101 102 103 52 53 53 54 55 55 56
95th 100 101 102 104 105 106 107 56 57 57 58 59 59 60
99th 108 108 109 111 112 113 114 64 64 65 65 66 67 67
2 50th 85 85 87 88 89 91 91 43 44 44 45 46 46 47
90th 98 99 100 101 103 104 105 57 58 58 59 60 61 61
95th 102 103 104 105 107 108 109 61 62 62 63 64 65 65
99th 109 110 111 112 114 115 116 69 69 70 70 71 72 72
3 50th 86 87 88 89 91 92 93 47 48 48 49 50 50 51
90th 100 100 102 103 104 106 106 61 62 62 63 64 64 65
95th 104 104 105 107 108 109 110 65 66 66 67 68 68 69
99th 111 111 113 114 115 116 117 73 73 74 74 75 76 76
4 50th 88 88 90 91 92 94 94 50 50 51 52 52 53 54
90th 101 102 103 104 106 107 108 64 64 65 66 67 67 68
95th 105 106 107 108 110 111 112 68 68 69 70 71 71 72
99th 112 113 114 115 117 118 119 76 76 76 77 78 79 79
5 50th 89 90 91 93 94 95 96 52 53 53 54 55 55 56
90th 103 103 105 106 107 109 109 66 67 67 68 69 69 70
95th 107 107 108 110 111 112 113 70 71 71 72 73 73 74
99th 114 114 116 117 118 120 120 78 78 79 79 80 81 81
6 50th 91 92 93 94 96 97 98 54 54 55 56 56 57 58
90th 104 105 106 108 109 110 111 68 68 69 70 70 71 72
95th 108 109 110 111 113 114 115 72 72 73 74 74 75 76
99th 115 116 117 119 120 121 122 80 80 80 81 82 83 83
7 50th 93 93 95 96 97 99 99 55 56 56 57 58 58 59
90th 106 107 108 109 111 112 113 69 70 70 71 72 72 73
95th 110 111 112 113 115 116 116 73 74 74 75 76 76 77
99th 117 118 119 120 122 123 124 81 81 82 82 83 84 84
8 50th 95 95 96 98 99 100 101 57 57 57 58 59 60 60
90th 108 109 110 111 113 114 114 71 71 71 72 73 74 74
95th 112 112 114 115 116 118 118 75 75 75 76 77 78 78
99th 119 120 121 122 123 125 125 82 82 83 83 84 85 86
9 50th 96 97 98 100 101 102 103 58 58 58 59 60 61 61
90th 110 110 112 113 114 116 116 72 72 72 73 74 75 75
95th 114 114 115 117 118 119 120 76 76 76 77 78 79 79
99th 121 121 123 124 125 127 127 83 83 84 84 85 86 87
10 50th 98 99 100 102 103 104 105 59 59 59 60 61 62 62
90th 112 112 114 115 116 118 118 73 73 73 74 75 76 76
95th 116 116 117 119 120 121 122 77 77 77 78 79 80 80
99th 123 123 125 126 127 129 129 84 84 85 86 86 87 88
 Blood Pressure Levels for Girls by Age and Height Percentile

BP Systolic BP (mmHg) Diastolic BP (mmHg)

Age Percentile Percentile of Height Percentile of Height
(Year) 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
11 50th 100 101 102 103 105 106 107 60 60 60 61 62 63 63
90th 114 114 116 117 118 119 120 74 74 74 75 76 77 77
95th 118 118 119 121 122 123 124 78 78 78 79 80 81 81
99th 125 125 126 128 129 130 131 85 85 86 87 87 88 89
12 50th 102 103 104 105 107 108 109 61 61 61 62 63 64 64
90th 116 116 117 119 120 121 122 75 75 75 76 77 78 78
95th 119 120 121 123 124 125 126 79 79 79 80 81 82 82
99th 127 127 128 130 131 132 133 86 86 87 88 88 89 90
13 50th 104 105 106 107 109 110 110 62 62 62 63 64 65 65
90th 117 118 119 121 122 123 124 76 76 76 77 78 79 79
95th 121 122 123 124 126 127 128 80 80 80 81 82 83 83
99th 128 129 130 132 133 134 135 87 87 88 89 89 90 91
14 50th 106 106 107 109 110 111 112 63 63 63 64 65 66 66
90th 119 120 121 122 124 125 125 77 77 77 78 79 80 80
95th 123 123 125 126 127 129 129 81 81 81 82 83 84 84
99th 130 131 132 133 135 136 136 88 88 89 90 90 91 92
15 50th 107 108 109 110 111 113 113 64 64 64 65 66 67 67
90th 120 121 122 123 125 126 127 78 78 78 79 80 81 81
95th 124 125 126 127 129 130 131 82 82 82 83 84 85 85
99th 131 132 133 134 136 137 138 89 89 90 91 91 92 93
16 50th 108 108 110 111 112 114 114 64 64 65 66 66 67 68
90th 121 122 123 124 126 127 128 78 78 79 80 81 81 82
95th 125 126 127 128 130 131 132 82 82 83 84 85 85 86
99th 132 133 134 135 137 138 139 90 90 90 91 92 93 93
17 50th 108 109 110 111 113 114 115 64 65 65 66 67 67 68
90th 122 122 123 125 126 127 128 78 79 79 80 81 81 82
95th 125 126 127 129 130 131 132 82 83 83 84 85 85 86
99th 133 133 134 136 137 138 139 90 90 91 91 92 93 93

BP, blood pressure

* The 90th percentile is 1.28 SD, 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD
over the mean.
For research purposes, the standard deviations in Appendix Table B–1 allow one
to compute BP Z-scores and percentiles for girls with height percentiles given in
Table 4 (i.e., the 5th,10th, 25th, 50th, 75th, 90th, and 95th percentiles). These height percen-
tiles must be converted to height Z-scores given by (5% = -1.645; 10% = -1.28; 25% = -0.68;
50% = 0; 75% = 0.68; 90% = 1.28%; 95% = 1.645) and then computed according to the
methodology in steps 2–4 described in Appendix B. For children with height percentiles
other than these, follow steps 1–4 as described in Appendix B.
Measurement
 Begin routine blood pressure (BP) measurement at 3 years of age.
 Correct cuff size depends on arm size. Practically speaking, correct
cuff size equals largest cuff that will fit on the upper arm with room
below for the stethoscope head.
 BP should be measured in the right arm of a relaxed, seated child.
 BP measurement by auscultation is the Gold Standard.
 BP by automated device correlates reasonably well with auscultation,
with practical advantages of rapid measurement remote from child
and elimination of reader error.
 If BP is high by automated device, repeat by auscultation.

BP Classification/Interpretation
BP is classified by systolic BP (SBP) and diastolic BP (DBP)
percentiles for age/sex/height. If SBP or DBP >90th percentile, repeat
twice at same office visit before interpreting result.

Normal BP: SBP and DBP <90th percentile

 Recheck in 1 year.
Prehypertension: SBP or DBP > 90th percentile to <95th percentile
or BP >120/80 mmHg to <95th percentile
 Recheck in 6 months.
 Begin weight management (as appropriate). Stage 1 Hypertension
(HTN): SBP and/or DBP >95th percentile to < 99th percentile plus 5
mmHg
 Recheck in 1 to 2 weeks.
 If BP remains at this level on recheck, begin evaluation and treatment
including weight management if appropriate.
Stage 2 HTN: SBP and/or DBP >99th percentile plus 5 mmHg
 Begin evaluation and treatment within 1 week, immediately if
symptomatic.

Systolic BP Percentile Tables

Since diastolic HTN rarely occurs without systolic HTN in children, the SBP
percentile tables on the next page can be used for HTN screening. If a child’s
SBP on screening is classified as prehypertension or HTN, then both SBP and
DBP percentiles should be determined using the tables in the complete report:
The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood
Pressure in Children and Adolescents. Pediatrics 2004 Aug;114(Suppl 2:)555-76;
or http://www.nhlbi. nih.gov/health/prof/heart/hbp/hbp_ped.htm.

Directions for Use of Tables

1. Heights in the table are given for age at midyear. Use closest height
to interpret BP.
2. Prehypertension SBP > value from table (90th percentile) to < Stage
1 HTN value; or SBP >120 mmHg to < Stage 1 HTN value.
Stage 1 HTN SBP > value from the table (95th percentile) to < Stage
2 HTN.
Stage 2 HTN. SBP >value from table (99th percentile plus 5 mmHg)

For more information go to: www.nhlbi.nih.gov.

Appendix 1 Nomogram-Body Surface Area
Appendix 2 Conversion from conventional to SI units
Laboratory test Conventional SI To convert to
units units SI units
ALT (alanine units/l ukat/l ×0.01667
aminotransferase)
Albumin g/dl g/l ×10
Alkaline phosphatase units/l ukat/l ×0.01667
Aldosterone ng/dl nmol/l ×0.0277
Amylase, serum units/l nkat/l ×0.01667
Bilirubin mg/dl umol/l ×17.1
Calcium, serum mg/dl mmol/l ×0.25
mEq/l ×0.50
Calcium, urine mg/24 h mmol/24 h ×0.025
Cholesterol, total mg/dl mmol/l ×0.02586
Creatinine mg/dl umol/l ×88
Glucose, plasma mg/dl mmol/l ×0.05551
Iron (total) and ug/dl umol/l ×0.179
total iron-binding
capacity
Magnesium mg/dl mmol/l ×0.411
Parathyroid hormone pg/ml ng/l No conversion
Phosphorus mg/dl mmol/l ×0.323
Urea, plasma (BUN) mg/dl mmol/l ×0.357
Uric acid mg/dl umol/l ×59.48
1,25-dihydroxyvitamin D pg/ml pmol/l 2.6
25-hydroxyvitamin D ng/ml nmol/l 2.496
Appendix 3 Bipolar renal length and renal volume
Age Mean ± SD (cm) Renal volume ± SD (ml)
1 months 4.3 ± 0.6 9.7 ± 4.7
3 months 4.7 ± 0.7 12.1 ± 6.0
6 months 5.5 ± 0.7 18.3 ± 7.0
9 months 5.6 ± 0.6 19.6 ± 6.8
1 year 5.7 ± 0.4 21.3 ± 5.5
2 years 6.1 ± 0.7 25.3 ± 8.2
3 years 6.7 ± 0.6 31.3 ± 10.0
4 years 6.8 ± 0.6 32.9 ± 9.1
5 years 6.7 ± 0.6 33 ± 8.9
6 years 6.8 ± 0.6 34.2 ± 9.4
7 years 6.7 ± 0.4 44.6 ± 12.7
8 years 7.2 ± 0.6 49.8 ± 14.8
9 years 7.6 ± 0.7 56.2 ± 16.7
10 years 8.0 ± 0.6 58.0 ± 16.2
11 years 8.0 ± 0.7 59.8 ± 17.3
12 years 8.5 ± 0.8 61.4 ± 16.5

Appendix 4 Normal values for GFR

Age Mean GFR ± SD,ml/min/1.73m2
Neonate 27-31 weeks gestation
1 week 19.95 ± 9.30
2 weeks 22.11 ± 14.91
3 weeks 24.64 ± 10.88
4 weeks 27.66 ± 12.66
Neonate < 34 weeks of gestation
1 week 15.3 ± 5.6
2-8 weeks 28.7 ± 13.8
> 8 weeks 51.4
Neonate > 34 weeks of gestation
1 week 41 ± 15
2-8 weeks 66 ± 25
> 8 weeks 96 ± 22
Children and adolescents
2-12 years (male and female) 133 ± 77
13-21 years (male) 140 ± 30
13-21 years (female) 126 ± 22
Appendix 5 Important formula
Formula Remarks

Estimated glomerular K × height (cm) Staging and management

Filtration rate (GFR) Serum Cr (mg/dl) (K= 0.43) of CKD

Serum anion gap Na+ - (Cl- + HCO3-) Normal value 6-12 mEq/L

Urine anion gap Na+ + K+ - Cl Index of urinary NH4

excretion

Plasma osmolality 2(Na+) + BUN(mg/dl) / 2.8 + Normal 280-285 mOsm/kg

glucose /18

Free water deficit Total body water × (Na+ Total body water=
concentration / 140) - 1 0.6 × wt (kg)

Transtubular potassium gradient Urine K+ × plasma osmolality Reflece aldosterone mediated

Plasma K+ × urine osmolality Plasma K+ × urine osmolality diatal K+ secretion. Normal
(TTKG) <2.5 during hypokalemia; >7
in hyperkalemia

Fractional excretion of Na+ Urine Na+ × plasma creatinie <1% in volume contraction
plasma Na+ × urine creatinine with appropriate renal Na+
retention

Calcium correction for 0.8 × (4.0 – patient albumin) +

hypoalbuminemia serum creatinine

Change in sodium concentration (infusate Na+ - serum Na+) ÷ Infusate Na+: concentration
following infusion of 1L solution (TBW + 1) of Na+ in fluid infused

Expected bladder capacity < 2 yrs: [weight in kg × 7] ml

> 2 yrs: [(age in yrs + 2)×30] ml
Appendix 6 Preparation of alkali and phosphate supplements
Preparation Dosage Formulation Remarks

Bicitra 2–3 mEq/kg/24 h 100 g sodium 1 ml = 1 mEq of base

PO ÷ Q6–8 h citrate equivalent
60 g citric acid per L

Polycitra 2–3 mEq/kg/24 h 110 g potassium 1 ml = 2 mEq base

PO ÷ citrate, 100 g equivalent, 1 mEq
Q6–8 h sodium Na, 1 mEq K; sour taste and
citrate, 66.8 g citric laxative effect
acid per L

Polycitra-K 2–3 mEq/kg/24 h 220 g potassium 1 ml = 2 mEq base

PO ÷ citrate, 66.8 g citric equivalent, 2 mEq K; K salts
Q6–8 h acid per L should be used with caution
in patients with renal
functional impairment

Shohl solution 2–3 mEq of 140 g citric acid, 1 ml = 1 mEq base

bicarbonate/ 90 g sodium equivalent
kg/24 h PO ÷ citrate per
Q6–8 h 1,000 L

Joulie solution 1,000 ml = 136 g 1 ml = 30 mg PO 4 (1.6

dibasic sodium mmol) Use with caution in
phosphate, patients with renal
58.8 g phosphoric impairment. Be aware of
acid sodium and/or potassium
load when supplementing
phosphate. May cause
nausea, vomiting, abdominal
pain, or diarrhea

Sodium 2–3 mEq/kg/d. IV ‘s’ Solution 1 ml = 0.9 mEq base,

bicarbonate Higher doses (7.5 %) 325 mg = 4 mEq, 650 = 8
required Tabs: 325, 650 mg mEq bicarbonate. Watch for
for patients with hypernatremia, tetany,
proximal RTA hypokalemia

Potassium 1–2 mEq/kg/d 10 % Syrup Kesol: 5 ml = Injection potassium chloride

chloride solution (Potchlor), 13 mEq of potassium (15 %, 10 ml/ampoule), 1 ml
15 ml = 20 mEq = 2 mEq of potassium
of potassium

Table continued
Appendix 6 (continued)
Preparation Dosage Formulation Remarks
Calcium 45–65 mg of 250, 500 mg 1,000 mg = 22.3 mEq base.
carbonate elemental calcium/ tablets Side effects: constipation,
kg/24 h PO ÷ QID hypercalcemia,
hypophosphatemia,
hypomagnesemia, nausea,
vomiting, headache, and
confusion. Administer with
plenty of fluids. As a
phosphorus-lowering agent,
administer with meals
Calcium 0.5 ml/kg/dose, 10 % solution 1 ml = 100 mg calcium
gluconate slow IV. Max IV gluconate = 9 mg elemental
infusion rates: IV Ca. Slow infusion and
push: Do not monitor for bradycardia and
exceed 100mg/min hypotension
(1ml/min). IV
infusion: 120–240
mg/kg/h (1.2–2.4
ml/kg/h)

Calcidiol Children < 20 kg: 0.25, 0.5 microg Monitor plasma levels of
(alphacalcidiol): 0.05 ug/kg/d. 1 mg calcium, phosphorus,
1 hydroxycho- Children > 20 kg alkaline phosphatase, and
lecalciferol body: 1 ug/d parathyroid hormone. Side
effects: polydipsia, polyuria,
constipation, hypotonia,
metastatic calcification,
headache, vomiting

Calcitriol Renal failure: 0.25 ug, 0.5 microg Active and most potent
(1,25dihydroxy- 0.01–0.05 ug/ vitamin D metabolite
cholecalciferol) kg/24 h available. Side effects same
as calcidiol
Appendix 8 Normal values for serum creatinine
Age Range (mg/dl)
Cord 0.6 – 1.2
Newborn 0.3 – 1.0
< 3yrs 0.17 – 0.35
3-5 years 0.26 – 0.42
5-7 years 0.29 – 0.48
7-9 years 0.34 – 0.55
9-11 years 0.35 – 0.64
11-13 years 0.42 – 0.71
13-15 years 0.46 – 0.81
Adult male 0.7 – 1.3
Adult female 0.6 – 1.1
 INDEX
A Congenital oligomeganephronia 25
ABPM 317 Contrast enhanced voiding ultrasonogra-
Acetazolamide 274 phy 554
Acidification of urine2 CoQ10 related mitochodropathies 168
ADAMTS13 362 COVID vaccines 399
Aldosterone deficiency 254 Cr-EDTA 560
Anion gap 267 Cystatin C 380
Antenatal hydronephrosis 405 Cystic tumors 440
Apparent mineralocorticoid excess 330 Cystinosis 452
Ask-upmark kidney 25 D
B DCE-MRI 559
Barrington nucleus 520 Deferment of Immunization 396
Bicarbonate loading test 459 Denys-Drash syndrome 151
BOLD MRI 559 Detrusor overactivity 544
Bosniak classification 440 Development of kidney 13
Botulinum 526 Dietl’s crisis 410
Bowed leg 484 Difficult to treat steroid sensitive disease
Bowel bladder diary 523 126
BP index 317 Dipping 317
Brodel effect 402 Drug-associated immune complex
Burosumab 487 vasculitis 177
DSE 534
C Dual energy X-ray absorptiometry 482
Calciphylaxis 388
Captopril renography 566 E
Caroli disease 425 EAST syndrome (SeSAME syndrome)
Causes of recurrent gross hematuria 96 466
Chlorambucil 139 Ectopic Kidney28
Chronic Valsalva 528 Eculizumab 374
Churg Strauss syndrome 200 EDOUF 539
CIMT (carotid intima-media thickness test) 335 Endoscopic deroofing 420
Cinacalcet 487 Enuresis risoria 543
cloudy urine 59 Eponymous syndromes 433
CNI 140 Euvolemic hyponatremia 248
Cobra head appearance 420 Evaluation for HTN (MONSTER) 334
F K
factitious syndrome by proxy 57 Klotho 478
Fanconi Syndrome 452 L
Fanconi syndrome 461 Leech method 523
Filtration Barrier 05 Leigh syndrome 169
fMRU 559 Lesch Nyhan syndrome 500
Fresier syndrome 167 L-FABP-Liver type fatty acid binding
FRIED 251 protein 291
Liddle syndrome 330
G
Liddle’s syndrome 274
Galloway and Mowat syndrome 169
Lipoprotein apheresis 157
Gammopathy 113
Loin mass 419
Gitelman’s syndrome 274 Looser zones 482
Glomerular and tubular proteinuria 60
Glomerular cysts 430
M
MAHA 370
Glomerular filtration rate (GFR) 15
Masked HTN 317
Glomerulocystic kidney disease (GCKD) 446
McIsaac Criteria 94
Glomerulocystic kidney disease 423
Medullary cystic dysplastic kidney26
Goodpasture syndrome 102 Medullary Sponge Kidney 26
Gordon syndrome 330 Megaureter 421
H Membranous Nephropathy (MN) 119
Haploinsufficiency 362 Meningocele closure 548
Holding maneuver 521 Mesenchymal stem cells (MSCs) 157
Hungry bone syndrome 488 MEST-C Score 189
Micky-Mouse 54
Hyper filtration injury 377
Micropenis 34
Hypercaloric diet 172
Midstream urine 40
Hyperkalemia 253
Mirabegron 526
Hyperkalemic periodic paralysis 253
Mitrofanoff 549
Hypervolemic hyponatremia 248 Multicystic dysplastic kidney (MCDK) 434
Hypomagnesemia 264 Multicystic kidney 406
Hypospadias 33 Multilocular cystic nephroma 429
Hypovolemic hyponatremia 248
N
I Nail patella syndrome 168
Ileal conduit 549 Nail Patella syndrome 443
Infective endocarditis 96 Nail-Patella syndrome 151
IVC collapsibility index 129 NC grade1 568
J Nephronophthisis 431
Jogger’s hematuria 55 Neuromodulator 526
Juxtaglomerular apparatus 06 NGAL 291
O Rodeck vesicoamniotic shunt 415
Ochoa 543 ROS 401
Ofatumumab 142 S
Ofatumumab 156 Sacral nerve stimulation 530
Onuf nucleus 521 Schwartz and Bartter clinical criterion 246
Oscillometric device 316 Serum biomarkers 213
P SIADH 238
Pectus excavatum 480 SIADH 246
PEX 373 Simple renal cyst (SRC) 434
Phimosis (Non-retactile foreskin) 35 Simple renal cyst 25
Pierson syndrome 168 Single kidney 23
Pierson’s syndrome 151 Snellen classification 564
Plasmapheresis (PEX) 108 spinal reflex 10
PLCE 1 168 St. vincents courtesy 521
Pneumococcal vaccine 147 Syndromic cysts 426
Propiverine 526 T
prune belly syndrome 35 Thomsen Friedreich (T) antigen 99
Prune belly syndrome 422 Thomsen-Friedenreich Antigen- T antigen 363
Q Tolterodine 526
Quick-Wee method 40 Tris-Hydroxymethyl Aminomethane
(THAM) 269
R Trospium 526
Rachitic rosary 480 TTP 363
Radionuclide cystography (RNC) 567
RASSI 157 U
Reabsorptive Hypercalciuria 499 Urinary biomarkers 213
Urodynamic study 550
Red diaper syndrome 60
Uroflow study 524
Red eye syndrome 388
Uroflowmetry 546
Reflux nephropathy 413
Uromodulin 443
Refractory KD 196
Urotherapy 524
Renal angina index 293
Renal dysplasia 25 V
Renal hypoplasia 25 Vaccination 395
Renal physiology 14 Varicella 145
Renal solute load (RSL) 233 Vasopressin antagonist 248
Renal tubular buffer system20 Vesicoureteric reflux 417
Renal tubular dysgenesis 26 W
Renal tubule with syndrome 448 Washout/excretory phase 565
Renin Angiotensin Aldosterone (RAAS) system 18 Water deprivation 470
Resistant HTN 317 White coat hypertension 317
Rituximab 141, 155 Williams syndrome 437