EMBRYOLOGY AND DEVELOPMENT

OF KIDNEY

Dr. Ranjitha . S
NEPHROLOGY RESIDENT
 Contents
• Basic concepts

• Stages of kidney development

- Nephron, collecting system, vasculature
- Urinary bladder, urethra

• Molecular mechanisms in kidney development

• Role of RAAS in kidney development
• CAKUT and various anomalies
BASIC CONCEPTS
 INTRAEMBRYONIC MESODERM
• Intraembryonic mesoderm is subdivided
into

• Paraxial mesoderm

• Intermediate mesoderm

• Lateral mesoderm
 INTRODUCTION
• The embryonic structures that play important
role in development of GUS are

• 1.intermediate mesoderm

• 2.cloaca
 CLOACA
• Primitive urogenital
sinus
• 1) vesico –urethral
canal
• 2)definitive urogenital
sinus
-pelvic part
-phallic part
 INTERMEDIATE MESODERM
• After folding of the embryonic disc , the intermediate
mesoderm forms a bulging on the posterior abdominal wall,
called the NEPHROGENIC CORD /UROGENITAL RIDGE
• It extends from the cervical region to the sacral region of the
Embryo.
 Stages of kidney development
• The human kidney develops in 3
succesive stages (rostral to caudal)
 PRONEPHROS
 MESONEPHR0S
 METANEPHROS

•They are aligned adjacent

to the Wolfian/Nephric
duct
 PRONEPHROS
• It develops from
rostral most
part
• 22 days of
gestation
• Functions in larval
stages`of amphibians
and fish.
• Regress by 5 weeks
 MESONEPHROS
• Develops caudal to
pronephros
• Series of tubules drain
into nephric duct called
mesonephric duct
• Disappears by 4th
month
• Some of its cells give rise
to adrenals and gonads
• Ureteric bud formation
 METANEPHROS
• The metanephros-major
part which forms kidney in
humans
• Reciprocal inductive
interactions that occur
between the metanephric
mesenchyme (MM) and the
epithelial ureteric bud (UB)
• UB is first visible as an
outgrowth at the distal end
of the wolffian duct at
approximately 5 weeks
of gestation
 DEVELOPMENT OF THE NEPHRON
• The MM becomes
histologically distinct from the
surrounding mesenchyme and
is found adjacent to the UB.
• Invasion - UB to branch into a T-
tubule
• Reciprocal signals from UB to
MM- CONDENSATION
• Process mediated by
GDNF/cRet/Wnt- 11 signalling
pathway
• After condensation, a
subset of MM cells
aggregates adjacent and
inferior to the tips of the
branching UB.

• These are pretubular

aggregates, undergo
mesenchymal-to-
epithelial conversion to
become the renal vesicle.

• The renal vesicle forms

the glomerulus and
components of the
nephrogenic tubules .
• UB branching and
consensation further
subdivides kidney into an
outer cortical region, where
nephrons are being
induced, and an inner
medullary region,where the
collecting system will form.
• As growth
continues,successive groups
of nephrons are induced at
the peripheral regions of the
kidney known as the
NEPHROGENIC ZONE.
Remarkably, this process is repeated 600,000 to 1 million times in each
developing human kidney as new nephrons are sequentially born at
the tips of the UB throughout fetal life.
• Podocyte and
bowman capsule
formation
• GBM
• Podocyte maturation
and slit diaphragm
formation
• Tubules
 DEVELOPMENT OF THE COLLECTING
SYSTEM
• The collecting ducts are all derived from the original UB.
• The branching is highly patterned
• The uretric bud undergoes repeated branching to form
ureters ,renal pelvis,major calyces,minor calyces and
collecting ducts.
 RENAL STROMA AND
INTERSTITIAL POPULATIONS
• Stromal cells also derive from the MM.

• Cortical stromal cells exist as a thin layer

beneath the renal capsule and medullary
stromal cells populate the interstitial
space between the collecting ducts and
tubules
• Cortical stromal cells also provide signals
required for UB branching and patterning
of the developing kidney.
• A reciprocal signaling loop from the UB exists
to properly pattern stromal cell populations.
• Stromal cells differentiate into peritubular
interstitial cells and pericytes.
 DEVELOPMENT OF THE
VASCULATURE
• Includes specialized glomerular capillary
system, the vasa recta and peritubular
capillaries.
• Vasculogenesis refers to de novo
differentiation of previously nonvascular cells
into structures that resemble capillary beds.
• Angiogenesis refers to sprouting from the
early vascular beds to form mature vessel
structures including arteries, veins, and
capillaries.
DEVELOPMENT OF BLADDER
Development of Trigone of Urinary Bladder
Development of Urethra
 RENAL ASCENT
• During the 5th and 6th weeks- kidneys lie in the pelvis with
hila pointed anteriorly.
• By 7th week ,the hilum points medially and the kidneys
are loacted in the abdomen
• 9 th week, retroperitoneal position at the level of L1
• mean time kidneys have completed rotation and hila
now face anteromedially
• As the kidney ascends it receives new segmental
arteries from aorta and loses those vessels below
.Thus sometimes there is more than one renal artery.
Timeline of kidney embryology
Molecular mechanisms of renal development

• Molecular regulation of ureteric budding

 Role of RAAS in kidney development
• RAAS axis required for normal renal development Genetic
inactivation of RAAS at any step, or pharmacologic
inhibition leads to complex developmental injury to the
kidneys
• like fewer glomeruli, thinner cortex, dilated tubules, thicker
arterioles and arteries, lack of vascular bundles, papillary
atrophy, shorter capillary length and volume in cortex and
medulla.

• Role of the renin-angiotensin system in kidney development and programming of adult blood pressure
Lucas F Almeida et al. Clin Sci (Lond). 2020.
• ANGII-AT1 interaction forms (VEGF) and angiopoietins
from podocyte and epithelial cell important in late
stages of glomerular and cortical capillary growth and
medullary vascular bundle formation and patterning.
• RAAS-induced injury is associated with lower
glomerular filtration rate (GFR), lower renal plasma
flow, kidney fibrosis, up-regulation of sodium
transporters, impaired sodium excretion and salt-
sensitive hypertension.
CONGENITAL ANOMALIES OF
THE KIDNEY AND URINARY
TRACT (CAKUT)
 CLASSIFICATION
1. Anomalies of renal parenchyma
a. renal dysplasia/ hypoplasia
b. renal agenesis
c. cystic renal diseases
d. renal tubular dysgenesis

2. Disruption of normal embryologic migration of kidneys

a. renal ectopia
b. fusion anomalies

3. Anomalies of collecting system

a. Complete or partial duplication of collecting system
b. Junction obstructions
c. Anomalies of ureter (megaureter, ectopic ureter, ureterocele or vesicoureteral reflux)
d. Bladder exotrophys
e. Posterior urethral valve
Hellenic NephrologyAn overview of kidney diseases in childrenN. Printza F. Papachristou 1st Pediatric Department, Hippokratio General Hospital, Aristotle
University, Thessaloniki, Greece
 Congenital anomalies
1. Anomalies of number
2.Anomalies of ascent
3. Anomalies of form and fusion
4. Anomalies of rotation
5.Anomalies of collecting system
6.Anomalies of renal vasculature
 EPIDEMOLOGY
• Identified in fetal ultrasonography is 0.3 to 1.6 per
1000 liveborn and stillborn infants
• Nonrenal malformations in approximately 30% of
cases.
• Most common cause of all birth defects, making up
20%- 30% of all defects in prenatal period
• 30% to 50% of all cases of end- stagekidney disease
(ESKD) in children.
• 2.2% of all cases of ESKD in adult .
Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system

(1990-1998).AUQueisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J SOArch Gynecol Obstet. 2002;266(3):163 .

 PATHOGENESIS OF CAKUT
• Genetics of CAKUT are complex
• 30% of affected individuals, these
malformations occur as part of a multiorgan
genetic syndrome.
• More than 200 syndromes
THE ENVIRONMENT IN UTERO AND
CAKUT
 Renal parenchymal malformations
• 1.Bilateral renal agenesis
 first recognised in 1671
 Male predominance
 Increase maternal age.
 prevalence is 1 in 10,000 births.
 40% are still born
 Most born alive do not survive beyond 48
hours
 Anuria after the 1st 24 hours without distention
of the bladder should suggest renal agenesis.
 Unilateral Renal Agenesis
• 1 in 520 to 1000 births.

• mutations in uroplakin-IIIa are found.

• no ureter, and the ipsilateral half of the bladder

trigone, ipsilateral genital structures also absent

• The remaining kidney is usually hypertrophic, but it

may be ectopic, malrotated, or hydronephrotic with a
megaureter.
 Renal dysplasia and hypodysplasia
• Renal dysplasia - presence of malformed, immature
kidney tissue elements .

• Characterised by decreased number of nephrons, and

metaplastic transformation of metanephric mesenchyme
to cartilage and bone .

• unilateral or bilateral and occurs in 2 to 4 per 1000

births. The male-to-female ratio for bilateral renal
dysplasia is 1.3:1 and for unilateral dysplasia is 1.9:1 
 Multicystic dysplasia
• It consists of a numerous
noncommunicating cysts separated by
dysplastic tissue

• most commonly detected by routine

antenatal screening.

• Most infants with unilateral MCDK are

asymptomatic.

• mutations in the CHD 1L,

ROBO2,HNF1B, and SALL1 genes 
 Supernumerary kidney
• Its truly an accessory organ
with is own collecting
system,blood supply and
encapsulated parenchymal
mass.
• Only 100 cases reported
• Left side
• Affects equally men and
women
 Irregular Kidneys
• Irregularity of the renal outline may result
from fetal lobulation or a “dromedary
hump,” neither of which has any functional
implications.
 Anomalies of
ascent
• Simple renal ectopic
 found in pelvis,iliac,
abdomen ,thorax and
crossed .
 1 in 900.
 Left side is more
common.
 Associated
anomalies
 Anamolies of form and fusion
• 1.crossed renal ectopia with or without fusion
 Horseshoe Kidney
• If both kidneys are low, they may join at the
lower pole and are usually drained by two
ureters.
• 1 in 400 to 1800 births and is more common in
males (2 : 1).
• 90 percent of cases, fusion occurs at the lower
poles
• Patients present, if at all, with complications of
reflux, obstruction, or stone formation.
• Two theories -
• 2-8 times more likely
to have wilms tumor.
• 7% in turners
syndrome
• Associated congenital
anomalies
Anomalies of the collecting system
1.Megacalycosis-
 Non obstructive enlargement of calyces
resulting from malformation of the renal
papillae.
 Males 6:1,whites
 VUR
• Primary VUR – incompetent or inadequate
closure of ureterovesical junction with failure
of antireflux mechanism due to short
intravesical ureter
• up to 15 percent of prenatal hydropnephrosis
• Ranges over 30 to 45 percent for children
with febrile urinary tract infections
• females were twice as likely to have reflux as
males
 Extrarenal calyces
• Major calyces as well as the renal pelvis
are outside the parenchyma.
• Failure of normal drainage may lead
to stasis,infection and calculi.
Congential ureteropelvic junction obstruction

• Reported incidence is 1 in 500 live births

• Most common anatomical cause of antenatal
hydronephrosis
• caused by anatomic lesions or functional disturbances
due to partial obstruction, that restrict urinary flow
across the UPJ, resulting in hydronephrosis
• Caused by intrinsic stenosis of the proximal ureter at
UPJ, and less commonly by extrinsic compression
(accessory renal artery) of the UPJ
 URETERAL ABNORMALITIES
1.Duplex Ureters
• 1 in 150 births
• unilateral duplication is six times more
frequent than bilateral.
• More common in girls.
 Ectopic Ureters

• Female-male ratio of 7 : 1
• The ectopic ureter comes from the upper
pole and inserts into the bladder more
distally and toward the bladder neck, or it
opens into the upper urethra.
• In females, the ureter may end in the
urethra, vagina, or vulva, and patients
present with incontinence, UTIs, or a
persistent vaginal discharge
 Ureterocele
• Ureteroceles are cystic dilations of the
terminal segments of the ureter and are
caused by maldevelopment of the
caudal ureter.
• females more than males (4 : 1)
 Megaureter
• Isolated dilation of the ureter does not necessarily imply
obstruction.
• There are three broad groups of conditions
• 1. Obstruction of the ureter itself.
• 2. Bladder outflow obstruction, with secondary ureteral
obstruction.
• 3. A dilated but nonobstructed ureter this may be
caused by
an adynamic segment of the lower ureter .
BLADDER ABNORMALITIES
 Posterior Urethral Valve

• Posterior urethral valves are the most

common cause of severe subvesical
obstruction in the male infant (but account
for only 10% of neonatal hydronephrosis).
• As a result, bilateral hydronephrosis
and megaureter occur.
• Obstruction is caused by a diaphragm
that extends from the floor to the roof
of the urethra at the apex of the prostate.
 Usg shows thickened
distended urinary bladder,
hydronephrosis, dilatated
posterior urethra
 Urethral Diverticulum

• Urethral diverticulum usually occurs in

boys and is rare.
• It may present with UTI, obstruction,
or stones.
• Two types - anterior and posterior.
 Anamolies of vasculature
 Aberrant,accessory or multiple vessels
• Multiple renal arteries is the correct term to
describe any kidney supplied by more than one
vessel.
• Aberrant vessels are those arteries that originate
from vessels other than the aorta or main renal
artery
• Accessory vessels denotes two or more arterial
branches supplying the same renal segment
 Renal artery aneurysm
• Incidence 0.1-0.3%
• Most are silent
• Pulsatile mass in the
region of renal
hilum or when an
abdominal bruit is
heard.
 REFERENCES
• 1.Rizaldy P.Scott,Yoshiro Maezawa,Jordan Kreidberg,Susan E
Quaggin.Embryology Of The Kidney.Brenner and Rector’s:The Kidney 11h
edition 2016:2-41.

• 2. Norman D. Rosenblum .Malformation of the Kidney: Structural and

Functional Consequences .Brenner and Rector’s:The Kidney 11th edition
2016:2294-2305

• 3. John O. Connolly and Guy H. Neild .Congenital Anomalies of the

Kidney and Urinary Tract.FEEHALLY 6 TH EDITION.

• 4. Vishram Singh.Development of Urinary System.Textbook of Clinical

Embryology:233-245.

• 5.UPTODATE ON CAKUT 2021

• 6. Congenital Anomalies of Kidney and Urinary Tract Hakan R. Toka,
MD, PhD,* Okan Toka, MD,† Ali Hariri, MD,‡ and Hiep T. Nguyen, MD