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Renal Biopsy in the Pediatric Patient

Isa F. Ashoor, Deborah R. Stein and Michael J. G. Somers
Division of Nephrology
Childrens Hospital Boston
Harvard Medical School, Boston, Massachusetts
USA
1. Introduction
Renal biopsy in children can be performed either by percutaneous, laparoscopic, or open
surgical approaches. As reported in a recent large pediatric series (Hussain et al., 2010), the
percutaneous approach is by far the most commonly utilized, with the open approach
typically reserved for situations in which percutaneous biopsy may be relatively
contraindicated or there is the need for a large wedge of tissue. Increasingly, more centers
are reporting successful experience with laparoscopic approaches as an alternative to open
surgical biopsies (Caione et al., 2000; Luque Mialdea et al., 2006; Mukhtar et al., 2005).
Native renal biopsy should be performed in a child when kidney disease is suspected and
treatment decisions require confirmation, when staging or characterization of a known
kidney disease is warranted, or when the disease diagnosis is known but the utility of
further treatment is questioned. In contrast to adults, renal insufficiency in children is
more often secondary to sequelae from congenital or structural anomalies rather than
acquired diseases. As a result, loss of renal function is not unexpected and tends to
progress more slowly. Typically, children with such well-defined renal anomalies do not
undergo biopsy even as renal function declines, unless a new entity is thought to be
present.
On the other hand, children presenting with an acquired kidney condition, especially with
rapidly changing renal function or lack of response to empiric therapy, do require renal
biopsy to allow for accurate diagnosis and tailoring of therapeutic intervention. Moreover,
while relatively common medical conditions such as hypertension and diabetes mediate
much of the chronic kidney disease seen in adults, these conditions are rarer in children and
less likely to impact renal health in the pediatric patient, leading to a need for clinicians to
actually identify why kidney disease has arisen in the child.
In contrast to many adults, children and adolescents typically require significant
conscious sedation or even general anesthesia for successful renal biopsy. Consequently,
the risks of both the procedure and sedation/anesthesia must be considered when
determining whether to do the biopsy. There are several medical conditions that often
preclude biopsy. Although each case must be individually considered and there may be
an occasion when the information garnered at biopsy outweighs the potential risk, the
following situations are often considered contraindications or relative contraindications
for pediatric biopsy:

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Contraindications for biopsy:

Severe bleeding disorders such as hemophilia
Known abdominal malignancy
Multiple renal cysts or renal tumor preventing sampling of renal parenchyma
Compromised skin or skin infection overlying biopsy entry site
Uncontrolled hypertension, increasing the risk of post-operative bleeding
Relative Contraindications:
Massive ascites
Severe hydronephrosis
While some have challenged the safety of performing renal biopsy in a child with a solitary
kidney, current complication rates have decreased to such a degree that, if warranted for
diagnostic reasons and if being performed by experienced clinicians utilizing medical
imaging to visualize the kidney during biopsy, this is generally not considered to be a
contraindication.

2. Nuts and bolts: Logistics of planning and preparation for the biopsy
procedure
If no ultrasound has been obtained in the past or if there is concern that there may have been
an interval change in the kidney or urinary tract anatomy since the last imaging study, a
renal ultrasound is performed to assess for anomalies such as hydronephrosis, to confirm
location and number of kidneys, and to assess renal size prior to the biopsy. The point of the
ultrasound is to identify any anatomic reason why biopsy would be contraindicated or that
would alter the approach to the biopsy.
A complete blood count (CBC), coagulation panel including prothrombin time (PT) and
partial thromboplastin time (PTT), as well as a sample for type and screen to be held in the
blood bank are obtained, typically within 72 hours of the procedure. The CBC allows
baseline hematologic parameters to be ascertained in case there is concern regarding
bleeding or infection post-procedure and also confirms an acceptable platelet count prior to
an invasive procedure. The PT/PTT identifies any tendency toward a coagulopathy that
may increase the chances of a bleeding complication. Although transfusion post-biopsy is
rare, having a blood type and screen in the blood bank will expedite this process if it is
necessary, and especially if it is urgently required.
Informed consent is obtained from either the parent/guardian or the patient if the patient is
of legal age. The consent process must include explaining the risks of the procedure,
however rare, including bleeding, infection, and the potential need for surgery to control
bleeding or perform nephrectomy. In children less than 18 years of age who are cognitively
capable of understanding the rationale for the biopsy procedure, in addition to informed
consent from the parent or legal guardian, there is utility in obtaining assent from the child.
This documents that the patient was also involved in the decision to proceed with the
biopsy and underscores the need to keep the patient involved in a developmentally
appropriate fashion with the process.
Prior to the biopsy, the patient will need to fast for some period of time, depending on
whether sedation or anesthesia is being utilized and institutional protocols. Most children
should tolerate this period of time without the need for supplemental intravenous
hydration, but individual circumstance and clinical status must be reviewed to determine if
the usual period of fasting is likely to cause any untoward consequence; for instance, a child

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with diabetes insipidus or a child with a severe urinary concentrating defect would require
special hydration plans.

3. Nuts and bolts: Sedation or anesthesia for the pediatric renal biopsy
Local standards and individual clinician preference have the greatest impact on the type of
sedation or anesthesia for pediatric patients undergoing percutaneous renal biopsy. The
overwhelming majority of children are offered intravenous conscious sedation or some sort
of general anesthesia, with very few patients declining such measures and opting for local
anesthesia injected at the biopsy site alone. In rare cases of children with serious
contraindication or objection to sedation or anesthesia, verbal sedation has been used,
with the child talked through the procedure with the help of a child life specialist trained in
this approach (Hussain et al., 2003).
Case series from North American centers show that general anesthesia is most often
reserved for infants or very small children where lack of cooperation during the procedure
is a concern as well as in children whose airways may be at risk with sedation alone (Birk et
al., 2007; Simckes et al., 2000; Sweeney et al., 2006). This approach is not necessarily the case
worldwide and, in fact, a recent audit in the United Kingdom (Hussain et al., 2010) showed
6 of 11 centers routinely using general anesthesia for pediatric kidney biopsies.
Intravenous conscious sedation, sometimes termed deep procedural sedation, is usually
administered by a nurse or physician who has acquired expertise in various sedation
techniques and certification in pediatric advanced life support (Cravero et al., 2006; Mason et
al., 2009). The patients should receive continuous cardiorespiratory monitoring throughout the
procedure. A variety of agents may be utilized and the protocols are institution specific or
dependent on local resources.
Our institution has successfully employed a radiologist-supervised ketamine sedation protocol
for many solid organ biopsies (Mason et al., 2009). In this protocol, children receive an IV
Ketamine bolus (2 mg/kg) over a 5-minute period with concomitant administration of 0.005
mg/kg of IV glycopyrolate. The bolus of ketamine is immediately followed by a continuous
infusion of 25-150 mcg/kg/min of ketamine for the duration of the procedure. Patients older
than 5 years also receive 0.1 mg/kg of midazolam hydrochloride (maximum = 3mg) before the
initial bolus of ketamine. There have been no major adverse events reported with this protocol
and both patient and family satisfaction rates have been high.
Other published sedation protocols employ a combination of meperidine (1 mg/kg
maximum 50 mg) and diazepam (0.2-0.4 mg/kg), with ketamine reserved for additional
sedation if necessary (Hussain et al., 2003); midazolam 0.1 mg/kg with additional ketmaine
where required (Mahajan et al., 2010); or intravenous propofol (1 mg/kg/dose titrated to
effect) and fentanyl (1 g/kg/dose) (Birk et al., 2007). Again, local practice and clinician
familiarity and expertise with certain medications tend to influence the type of sedation
provided most successfully and is more critical than the use of any specific medication or
combination of medications.
Local anesthesia may be achieved by applying a topical anesthetic cream (EMLA, lidocaine
2.5% and pritocaine 2.5% or Ametop tetracaine 4%) (Hussain et al., 2003) or local infiltration
with 1% lidocaine. At our center, for local infiltration with lidocaine, 9 mls of lidocaine
are mixed with 1 ml of 8.4% sodium bicarbonate; this approach seems to decrease
complaints of burning at the site of infiltration, and this is employed regardless of the type
of sedation utilized.

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The majority of percutaneous renal biopsies performed under sedation are done outside the
operating room, usually in an interventional radiology suite, a procedure area with access to
ultrasound imaging, or in ward treatment rooms (Davis et al., 1998; Hussain et al., 2003;
Mason et al., 2009). Although there were initial concerns about providing sedation in such
settings for invasive procedures, our own experience and that of others have shown few
safety concerns. The Pediatric Sedation Research Consortium reported a large series of
30,037 sedation encounters from 26 centers, with data submitted on a variety of pediatric
procedures performed under sedation or anesthesia outside the operating room (Cravero et
al., 2006). This study demonstrated the overall safety of such procedures, with no deaths
and only one cardiopulmonary resuscitation event. The most commonly encountered
adverse event in this cohort was more than 30 seconds of oxygen desaturation to less than
90% by transcutaneous monitoring, and this only occurred in 1.5% of cases. Needless to say,
the safety and success of such programs depend on consistently following well-developed
protocols, the presence of certified providers throughout the procedure, and readily
available anesthesia services to handle unexpected complications.

4. Nuts and bolts: Performing the renal biopsy

As discussed above, institutional practice and resources often guide the location for
pediatric biopsies. For instance, in our center, biopsies are performed in an Interventional
Radiology suite with either nurses providing conscious sedation by protocol or Pediatric
Anesthesiologists providing general anesthesia. The use of sedation versus anesthesia
typically depends on the age of the patient, developmental and emotional factors, and any
co-morbid medical conditions. For instance, a very young child with nephrotic syndrome
and significant volume overload will likely warrant general anesthesia whereas a mature
adolescent undergoing a transplant biopsy may need little other than local anesthesia over
the biopsy site.
Biopsies are performed under sterile conditions. As a result, it is important for the
individual performing the biopsy to follow standard protocol for a sterile invasive
procedure including aseptic technique and wearing appropriate gowns, gloves, masks, and
eye protection.
Obtaining an adequate sample is crucial for any renal biopsy, but is even more imperative in
children undergoing biopsy where the logistics of the procedure may be more complicated.
Availability of a dissecting microscope to view each core obtained to assess tissue adequacy
is extremely useful to guide the number of cores needed. Presence of either a pathologist or
nephrologist experienced in identifying renal tissue under dissecting microscope is
obviously essential and should allow some estimation of tissue adequacy.
For a native renal biopsy, the child is placed in a prone position and typically the left kidney
is imaged to discern an acceptable biopsy site. In a transplant patient, the child will be
supine and the area immediately over the allograft is imaged. The skin overlying the area
most appropriate for biopsy needle introduction is marked during this process. Generally, a
site in the lower pole of the kidney is selected, away from the renal hilum and large vessels.
At this point, prior to proceeding further with the procedure, a pause or time-out is
worthwhile, with the individual performing the procedure reviewing aloud the patients
name, medical diagnosis, planned procedure including site of biopsy, and confirming that
informed consent has been obtained. All others in the procedure area should then verbally
identify themselves and their role in the procedure, for instance Jane Jones, RN performing

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sedation or John Smith, attending radiologist so that there is both acknowledged

consensus of the procedure to be done by all involved and understanding of the specific
roles of all the individuals present in the area.
The biopsy area is cleaned thoroughly with a betadine solution, and all areas outside the
sterile field are covered with sterile drapes. A local anesthetic such as lidocaine is injected at
the marked skin site. An initial wheal is made and then deeper infiltration performed,
following the anticipated path of the biopsy needle. A superficial dermatotomy is made over
the wheal, and the biopsy needle is advanced through this area.
Typically, most pediatric renal biopsies are now done with ultrasound guidance. If desired,
this allows use of a needle guide that helps to position the path of the biopsy needle along
the desired biopsy tract. It also allows for continuous monitoring of the position of the
needle during the procedure and allows for ready identification of structures such as bowel
or large vessels that must be avoided. Optimally, the individual performing the biopsy has
been trained in biopsy sonography as well, so that the same individual is controlling the
imaging and the needle placement; otherwise, there needs to be continuous communication
between the individual advancing the biopsy needle and the sonographer to be sure that
both agree as to the needle position and the target.
Local practice and available resources will determine the biopsy devices and needles used,
most of which are readily available from medical vendors. For most percutaneous pediatric
renal biopsies at our center, we use an 18-gauge needle and an automated biopsy device or
gun that is loaded with the needle. The desired throw -- or length of the biopsy needle
that gets propelled into the kidney when the device is engaged -- depends on the size of the
child and the size of the kidney being biopsied. For most children, a throw of approximately
2 centimeters allows for a safe biopsy with sufficient tissue but, in especially young children
or with small kidneys, a shorter throw may be needed to avoid the renal hilum or other
surrounding structures.
The needle is advanced to the selected site in the lower pole renal cortex under continuous
ultrasound guidance. Once the needle reaches the renal capsule, it is advanced slightly
further to enter kidney tissue. The biopsy device is then fired which allows the inner
hollow-core biopsy needle to deploy, cutting a piece of kidney tissue. The cutting needle is
then automatically ensheathed by an outer protective core. The entire biopsy needle device
is withdrawn from the kidney and the protective sheath withdrawn to expose the tissue
core. The biopsy sample is carefully transferred onto a saline-soaked gauze by rolling the
needle onto the gauze, and then the core is examined by the pathologist or nephrologist
under a dissecting microscope for quick estimation of tissue adequacy. During this time
following needle extraction, the physician performing the biopsy or another designee
applies pressure to the biopsy site.
This procedure is repeated until adequate renal tissue has been obtained for the biopsy
indication, depending on the patients medical condition and the studies to be performed on
the tissue. Typically, for native kidney biopsies, we obtain three cores of tissue to allow for
sufficient tissue for light microscopy, immunofluorescence, and electron microscopy. For
transplant biopsies, two cores are generally obtained since fewer studies are usually done.
As always, the size and adequacy of tissue cores obtained will specifically define the
number of cores needed for any patient. If adequate tissue is not obtained after three to five
passes of the needle, then there must be consideration of the risk of ongoing passes into the
kidney versus the benefits of obtaining more kidney tissue at this point in time.

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At completion of the entire biopsy procedure, pressure is applied externally over the biopsy
site for a minimum of 5 minutes. A post-biopsy ultrasound with Doppler imaging is then
performed to evaluate for any hematoma or active bleeding. If bleeding is observed,
pressure is maintained until there is evidence of stable imaging with no expanding
hematoma or determination is made that there needs to be some other intervention. The
dermatotomy site is covered with a sterile dressing that may be removed the following day.
This dressing is observed for any bleeding or drainage while it is in place.

5. Open renal biopsy in children

Rarely, an open renal biopsy is appropriate in children. Common indications for open renal
biopsy are listed in Table One. Some clinical scenarios where open biopsy is more common
include when attempts at a percutaneous biopsy have failed, when a wedge resection is
required for pathologic diagnosis, or when there is a bleeding disorder but the biopsy is
paramount to treatment decisions. Open biopsy is performed typically by a general surgeon,
urologist, or transplant surgeon in an operating room. Open renal biopsy will usually result
in exposure to general anesthesia or more prolonged sedation with longer post-procedure
recovery times, hence increasing health care delivery costs.

Failed percutaneous renal biopsy

Percutaneous renal biopsy deemed unsafe:

Uncontrolled hypertension

Bleeding disorder
Solitary native kidney with specific concerns for percutaneous approach
Anatomic abnormalities complicating percutaneous approach:

Horseshoe kidney

Pelvic kidney
Intraperitoneal renal allograft with specific concerns for percutaneous approach
Donor implantation biopsy at time of transplant
Biopsy performed concurrent with other surgical intra-abdominal procedure
Morbid obesity

Table 1. Common Indications for Open Renal Biopsy

There may be center-specific variation in the use of open biopsy depending on local
experience and expertise. Similarly, there may be changes in local practice regarding specific
clinical scenarios that may come to decrease the need for open renal biopsy. For instance,
several centers have published their experiences transitioning from open to percutaneous
biopsies of solitary kidneys and transperitoneal allografts (Mendelssohn & Cole, 1995;
Vidhun et al., 2003). In cases that may be considered higher risk for percutaneous approach,
most clinicians think it judicious to pay special attention to coagulation parameters, blood
pressures and serum creatinine in determining the optimal approach for renal biopsy (Davis
et al., 1998; Simckes et al., 2000). Similarly, in situations where a clinician is performing a
higher risk percutaneous biopsy, it would be warranted to ensure in advance that there is
availability of interventional radiology or surgical support services for unexpected
complications.

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6. Laparoscopic renal biopsy

Within the last decade, there has also been increased utilization of laparoscopic approach as
an alternative to traditional open biopsy. This approach has been well-established in
morbidly obese adults where the body habitus precludes percutaneous approach (Mukhtar
et al., 2005, as cited in Shetye et al., 2003). Unfortunately, obesity rates in children are at an
all-time high and show no signs of abating (Anderson & Whitaker, 2009; Broyles et al., 2010).
Obesity is also a frequent complication of steroid therapy commonly used in treating
various glomerular lesions and in maintenance immunosuppression for renal transplant
recipients who may come to require biopsy. Furthermore, in the face of the obesity
epidemic, we are increasingly recognizing the entity of obesity-related secondary focal
segmental glomerulosclerosis presenting with heavy proteinuria (Fowler et al., 2009).
Consequently clinicians may find an increasing population of obese children requiring
biopsy whose body habitus prevents a percutaneous approach.
Mukhtar et al (Mukhtar et al., 2005) reported their experience with two morbidly obese
children where initial attempts at percutaneous biopsy failed. The procedures were then
carried out laparoscopically with no major complications, and both children were
discharged home within 48 hours at significant cost savings compared to an open biopsy.
Two larger case series from Italy and Spain (Caione et al., 2000; Luque Mialdea et al., 2006)
also described successful experiences with laparoscopic renal biopsies in 20 and 53 pediatric
patients, respectively. Children in those series ranged in age from 13 months to 19 years.
The procedure was safe and successful in all but one patient in each series who required
conversion to an open biopsy. The mean hospital stay in both cohorts was 48 hours or less.

7. Differences between native and transplant biopsies in children

In most children > 20 kg, transplanted kidneys are typically placed extraperitoneally in the
lower abdomen within the iliac fossa. In smaller children, kidneys may need to be placed
intraperitoneally. In most pediatric renal transplant recipients, transplanted kidneys are far
more superficial than native kidneys and this must be kept in mind during biopsy to avoid
improper sampling or damage to the vascular structures. Again, ultrasound guidance
during the biopsy procedure will help to minimize these technical complications. In those
children with intraperitoneal allografts, care must be taken to avoid bowel or other
structures that may overlie the allograft.
Allograft biopsies are typically performed to evaluate for acute rejection, to assess for
recurrence of diseases such as Focal Segmental Glomerulosclerosis (FSGS), to define new
onset suspected glomerular disease, to assess extent of chronic allograft nephropathy, or to
document infectious insults such as BK virus nephropathy. Some centers may perform
interval protocol biopsies at set intervals to assess the allograft parenchyma. Processing
and staining of the biopsy samples from transplanted kidneys depends on the biopsy
indication (see section 10).

8. Post-biopsy monitoring in children

There are currently no standard guidelines established for post renal biopsy monitoring. The
standard of care in adult patients has included bed rest with close observation for up to 24
hours (Whittier & Korbet, 2004). In their retrospective analysis of 750 adult patients who
underwent native renal biopsy, Whittier and Korbet found an observation time of up to 24

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hours to be optimal, with an observation period of 8 hours or less missing up to 33% of

complications. There are, however, various clinical and social factors that impact any
specific patients circumstances and, as a result, the length of observation post-biopsy
should be somewhat individualized.
In children, there are also wide variations in practice for post-biopsy monitoring. For
instance, a survey of pediatric nephrologists in Japan (Kamitsuji et al., 1999) covering
complications in 2,045 native percutaneous renal biopsies revealed that no center allowed
discharge within 24 hours of the biopsy, with 67% of patients remaining in the hospital for
at least 4-8 days. The patients in this cohort had similar complication rates to other pediatric
series with shorter duration of observation, however, and the prolonged hospital stay was
attributed to local practice.
Over the last two decades, with increasing safety of percutaneous renal biopsy, particularly
when performed with an automated biopsy needle under real time ultrasound guidance,
more centers are moving towards short post-biopsy monitoring times for both native and
allograft renal biopsies in children. In fact, several centers in North America and Europe
have implemented same day renal biopsy in ambulatory or day clinical care units as
standard practice for low risk patients since the early 1990s (Birk et al., 2007; Hussain et al.,
2003; Sweeney et al., 2006). This trend has been associated with significant cost savings
compared to inpatient renal biopsies and comparable safety outcomes (Chesney et al., 1996;
Hussain et al., 2003; Lau et al., 2009; Simckes et al., 2000). In addition, several centers in
developing countries are reporting successful experiences with percutaneous renal biopsies
in the ambulatory setting, where it was initially promoted for logistical reasons associated
with limited inpatient bed space (Al Makdama & Al-Akash et al, 2006; Mahajan et al., 2010).
In most centers where pediatric renal biopsies are performed as an inpatient procedure,
there is consensus regarding the utility of bed rest in the supine position for a period of 3-6
hours post biopsy. Patients are asked to save their urine for gross inspection and most
centers allow the patient to stand to void if two consecutive post-biopsy urine samples are
negative for gross hematuria. Vital signs are usually monitored every 15-30 minutes in the
first 2 hours post biopsy and less frequently thereafter. Some centers provide intravenous
hydration until patients are fully awake and able to drink. Most centers utilize
acetaminophen for analgesia.
Local standards often dictate post biopsy laboratory investigations or imaging studies. In
our institution, biopsies are performed by nephrologists trained in renal sonography in the
presence of an interventional radiologist who can immediately assist if there is some
question or concern for an adverse event. As noted above, immediate post-biopsy images
are also obtained by ultrasound to assess for hematoma formation and to provide a postbiopsy baseline. Others employ routine post-biopsy ultrasound from 24 hours to two weeks
following renal biopsy in all patients to detect peri/intra renal hematoma formation with
consideration of Doppler studies to assess for arteriovenous fistula formation (Al Rasheed et
al., 1990; Kamitsuji et al., 1999; Mahajan et al., 2010), though it is unclear whether this
changes clinical care of the stable patient (Castoldi et al., 1994).
It is also our practice to observe patients for at least 6 to 8 hours post-procedure and to check
a hemoglobin and hematocrit level at 4-6 hours post biopsy and again the next morning as
long as there is no concern to warrant repeat laboratory work sooner. A hematocrit drop of
greater than 5-7%, severe abdominal or flank pain, gross hematuria that does not clear or
markedly improve within two to three voids, or any evidence of hemodynamic instability

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would prompt urgent renal imaging with an ultrasound to detect ongoing bleeding or
expanding hematoma formation.
In those centers that perform percutaneous renal biopsies in the ambulatory setting without
provision for hospital admission, the selection criteria for low risk patients generally include
normal or controlled blood pressure, normal pre-biopsy hematocrit and coagulation studies,
a competent care giver to monitor the patient after the procedure, and the familys
willingness to stay within a reasonable distance of the hospital for the first night post-biopsy
(Ogborn & Grimm, 1992). Following the biopsy, patients are typically monitored for 6-8
hours with strict bed rest for 1-3 hours. Patients are discharged home at the end of this
observation period if their urine is free of gross hematuria, their vital signs are stable and
they have no significant pain at the biopsy site (Birk et al., 2007; Hussain et al., 2003; Ogborn
& Grimm, 1992; Simckes et al., 2000).
The value of routine post-biopsy imaging studies is controversial, with several studies
suggesting the development of post biopsy perinephric hematomas is common and does not
negatively impact patient outcomes or change the need for patient care in most cases
(Castoldi et al., 1994; Vidhun et al., 2003). Detection of hematoma may also be a function of
sensitivity of the imaging technique employed. For instance, data from CT scanning post
biopsy reveals that perinephric hematoma is almost universal (Castoldi et al., 1994, as cited
in Ralls et al., 1987). Castoldi et al further attempted to stratify hematomas according to size
and correlate them with patient outcomes. In their retrospective analysis of 230 patients
where 218 underwent post-biopsy sonography within 72 hours, the incidence of
parenchymal, subcapsular, and perinephric hematomas combined was 42%. In the absence
of clinical signs of bleeding, no short or long-term adverse effects were reported and, even
in the presence of clinical signs of bleeding, serious complications only occurred in those
with large hematomas. Large hematomas were defined as those having a thickness greater
than 1 cm and length greater than 3 cm. Moreover, although these large hematomas were
found in 20 patients (9% of their total cohort), only 7 of these patients had more than a 7%
decrease in their post-biopsy hematocrit values. On the other hand, all hematomas with a
thickness less than 2 cm in their study had a favorable clinical course.
Davis et al (Davis et al., 1998) evaluated the utility of monitoring the post-biopsy change in
hemoglobin concentration to identify bleeding complications that were otherwise not
clinically apparent. In their retrospective review of 177 percutaneous renal biopsies (137
native, 40 transplant), hemoglobin measurements were obtained at 4-10 hours and 15-24
hours post biopsy. In their study, using a drop in hemoglobin levels of more than 16% of
baseline for instance from 10 g/dl to 8.4 g/dl -- served as a sensitive (100%) and specific
(98%) marker of major bleeding complication that required either transfusion or additional
monitoring. The change in post-biopsy hemoglobin was not associated with the presence of
gross hematuria or perinephric hematoma, which were considered minor complications in
this study.
Children are allowed to return to school within one to two days of biopsy, though
participation in physical education classes is usually avoided for one week. Children are
also encouraged to avoid contact sports or vigorous activities that might result in direct
trauma to the biopsy site for one week. Children are allowed to shower but immersion of
the biopsy site in water is not recommended until the dermatotomy site is scabbed over,
which typically occurs within 48 to 72 hours. In the immediate post-biopsy period, families
are instructed to contact their pediatric nephrologist urgently for new onset gross
hematuria, dysuria, pain at the biopsy site, or fever.

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9. Complications post-biopsy
Percutaneous renal biopsy as performed in most pediatric centers today with ultrasound
guidance and automated biopsy needles is an extremely safe procedure with few associated
minor and major complications. Those complications are summarized in Table 2.
Various factors such as indication for biopsy, operator experience, needle type, and number
of passes can affect the rate of post biopsy complications. In the large Japanese cohort of
2,045 percutaneous native renal biopsies (Kamitsuji et al., 1999), the rate of gross hematuria
was very low and comparable between patients in whom an automated biopsy needle was
used compared to the older Vim-Silverman needle in which the cutting core was advanced
manually (2.7% vs. 3%). On the other hand, in a retrospective analysis of 177 percutaneous
renal biopsies, Davis et al (Davis et el., 1998) noted a significantly higher rate of post-biopsy
hematoma in those procedures performed with an automated biopsy needle (Meditech
ASAP Automatic 15-G Core Biopsy System needle) compared to a non-automated device (14
G Franklin-Vim-Silverman needle or 15 G Trucut needle). However, the authors report the
use of CT scan or ultrasound for post-biopsy imaging in the automated group compared to
ultrasound only in the non-automated group, which might have led to increased detection
of hematomas in the former because of CTs higher sensitivity, rather than actual difference
related to the biopsy device. Simckes et al (Simckes et al., 2000) found a trend for the nonautomated Trucut needle to be the least traumatic compared to the modified Franklin-VimSilverman and automated spring-loaded needles in their cohort. In comparison, Webb et al
(Webb et al., 1994) reported significantly more total complications with the Trucut needle
compared to the automated biopsy needle, though the difference in major complications
was not significant. Most likely, clinical factors and operator experience play a larger role in
post-biopsy hematoma formation that the biopsy device itself.

Minor complications
Microscopic hematuria
Self-limited gross hematuria
Asymptomatic peri-nephric hematoma
Asymptomatic decrease in Hb
concentration
Self-limited arteriovenous fistula
Mild pain/ discomfort at biopsy site
Inadequate biopsy tissue and/ or
failed biopsy

Table 2. Complications Post-Renal Biopsy

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Major complications
Persistent gross hematuria
Symptomatic peri-nephric hematoma
causing hemodynamic instability
Significant decrease in Hb
concentration requiring blood
transfusion
Hypotension
Symptomatic arteriovenous fistula
Inadvertent damage to adjacent organs
(e.g. liver, intestine)
Severe abdominal and/ or flank pain
Urinary tract infection
Urinary tract obstruction
Acute Renal Failure
Allograft loss
Nephrectomy
Death

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No difference has been reported in complication rates between using a 14-G Biopty gun
needle or an automated 14-G Trucut needle, suggesting that needle size may influence the
rate of complications more than needle type (Webb et al., 1994). Along those lines, Vidhun
et al (Vidhun et al., 2003) have shown in renal allograft biopsies a higher incidence of
perinephric hematoma (43% vs. 13.3%) and macroscopic hematuria (29% vs. 2.3%) with
use of a 16-G versus an 18-G biopsy needle. Similar findings in native renal biopsies were
also reported from a large Brazilian cohort (Piotto et al., 2008). As such, Birk et al (Birk et
al., 2007) hypothesized that the slightly higher incidence of post-biopsy gross hematuria
(8.4%) in their cohort of 43 renal transplant recipients compared to previously published
reports (1.9-3.5%) was their use of a larger 16-G needle compared to an 18-G needle used
elsewhere.
With regards to other factors, several retrospective analyses have shown no significant
difference in complication rates whether the biopsy was performed as an outpatient or
inpatient procedure (Hussain et al., 2003, 2010; Simckes et al., 2000), under general
anesthesia or sedation (Durkan et al., 2006; Hussain et al., 2010; Webb et al., 1994), by a
supervised trainee or by an attending physician or consultant (Durkan et al., 2006; Simckes
et al., 2000), and between an intraperitoneal and extraperitoneal graft in the case of allograft
percutaneous biopsies (Vidhun et al., 2003).
Interestingly, in native percutaneous biopsies, one author (Hussain et al., 2003) observed a
trend for a higher incidence of gross hematuria post biopsy in those patients with a
histological diagnosis of IgA Nephropathy/ Henoch-Schonlein Purpura. In the case of renal
allografts, biopsies for urgent issues were noted to have a higher incidence of post biopsy
hematoma compared to protocol biopsies (Vidhun et al., 2003). Increased number of passes
was significantly associated with obtaining more adequate tissue for making a histological
diagnosis (Durkan et al., 2006), but with a slightly increased but not significant trend
towards hematoma formation (Simckes et al., 2000).
Through the decades, the safety of percutaneous renal biopsy has been verified in several
large pediatric case series. Death is extremely rare. One early review (Al Rasheed et al., 1990,
as cited in White, 1963) reported 17 deaths in more than 10,000 biopsies (0.17%). Similarly,
another large review at that time reported a mortality rate of 0.12% in 4000 biopsies
(Simckes et al., 2000, as cited in Dodge et al., 1962). On the other hand, Edelmann found no
deaths in a review of reports published between 1971-1976 of more than 1,700 percutaneous
biopsies in children (Simckes et al., 2000, as cited in Edelmann et al., 1992). This improved
safety profile continues to be reported in more recent series from North American and
various institutions in Europe and Asia (Al Makdama & Al-Akash, 2006; Birk et al., 2007;
Hussain et al., 2010; Kersnik Levart et al., 2001; Mahajan et al., 2010) and likely is mediated
by concomitant imaging at the time of biopsy decreasing the chances for catastrophic
hemorrhage or damage to vital organs other than the kidney.
Given the use of different definitions and thresholds to report complications, it is worth
noting, however, that rates of so-called minor and major complications post-biopsy are
somewhat difficult to compare between individual centers. For example, one study included
microscopic hematuria as a minor complication, a finding almost universally seen in all
patients undergoing renal biopsy (Al Rasheed et al., 1990). Some studies include gross
hematuria as a major complication, while others only include it if persistent and associated
with hemodynamic instability and transfusion requirement. In their audit of UK centers,
Hussain et al included 39 patients with gross hematuria in the major complication group

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Topics in Renal Biopsy and Pathology

while only 4 of them required blood transfusions (Hussain et al., 2010). Regardless of those
differences, most recent series report major complication rates in the 0-5% range and
minor complications rates in the 8-15% range, though most complications that are
reported in either category are of little immediate or long-lasting clinical significance to the
patients well-being.
Similar low complication rates also can be found with allograft biopsies. Benfield et al
(Benfield et al., 1999) reported data from 19 pediatric transplant centers on 86 children who
underwent 212 allograft biopsies. There were a total of 9 complications (4.2%) with only 4
(1.9%) requiring intervention. No patient lost kidney function or required nephrectomy after
graft biopsy. Vidhun et al (Vidhun et al., 2003) specifically analyzed complication rates in
adult-sized renal allografts in children and reported an overall complication rate of 16.1%,
consisting mostly of perinephric hematomas (13.4%), while the gross hematuria rate (2.7%)
was similar to the cohort reported by Benfield. Most of those hematomas (81.4%) were small
(< 1 cm), and no patient in that cohort required intervention related to post-biopsy
complications.

10. Pathologic findings

The ultimate goal of the renal biopsy is to obtain sufficient tissue to make a diagnosis or guide
therapy. Based on histologic assessment of the biopsy samples, therapeutic intervention may
be initiated or altered and important prognostic information may be gained.
It is crucial to obtain sufficient tissue to allow proper assessment by the pathologist. In certain
pediatric renal diseases, light microscopy may be the most critical element, such as in the child
with steroid resistant nephrotic syndrome in which the differential is minimal change disease
versus focal and segmental glomerulosclerosis. In others, such as IgA nephropathy,
immunofluorescence studies play a vital role and, in some, such as idiopathic
membranoproliferative glomerulonephritis, electron microscopy will be necessary to
supplement light microscopy and immunofluorescence results. Table Three summarizes the
key pathologic studies to obtain on biopsy samples based on suspected clinical diagnosis.
Table Four lists the histopathologic changes typically seen in several pediatric renal diseases.
Suspected or Known
Disease

Light
Microscopy

Immunofluorescence

Electron
Microscopy

IgA Nephropathy
Henoch-Schonlein
Purpura

X
Defines extent
and severity of
process

X
Necessary for
diagnosis

Suggested but not

required

Systemic Lupus
Erythematosus

X
Necessary to
identify
class/severity

X
Necessary to
diagnose Class V
(membranous)

Membranoproliferative
Glomerulonephritis

X
Necessary for
diagnosis

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Renal Biopsy in the Pediatric Patient

Thin Basement
Membrane Disease
Hereditary Nephritis
Alports
Nail Patella Syndrome

X
Necessary for
diagnosis

Minimal Change
Nephrotic Syndrome
Focal and Segmental
Glomerulosclerosis

ANCA associated
vasculitis
Anti-GBM disease
Rapidly progressive
glomerulonephritis

? May not be
crucial

Transplant Biopsies*

X **

*If suspected recurrent disease, see above disease categories for tissue processing recommendations.
** C4d crucial for diagnosis of acute antibody-mediated rejection

Table 3. Desired Pathology Studies Based on Suspected Diagnosis

Disease
Nephritis
IgA Nephropathy

Henoch-Schonlein Purpura

Systemic Lupus
Erythematosus
I: Minimal Mesangial

II: Mesangial Proliferative

III: Focal

IV: Diffuse

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Light Microscopy

Immunofluorescence

Focal or diffuse
mesangial
hypercellularity

Mesangial IgA deposits Focal mesangial

proliferation with
electron-dense
subendothelial deposits
Granular IgA
Immune deposits

Focal or diffuse
mesangial
hypercellularity,
crescents

Normal

Mesangial immune
deposits (Ig, C3, C4)

Increased mesangial Mesangial immune

matrix
deposits (Ig, C3, C4)

Electron Microscopy

Normal

Few or no subepithelial
or subendothelial
deposits
Less than 50% of
Mesangial deposits, few Focal, subendothelial
glomeruli involved subepithelial and
deposits
subendothelial deposits
(Ig, C3, C4)
Nearly all glomeruli Mesangial deposits, few Endothelial cell
involved, wire-loop subepithelial and
proliferation
appearancesubendothelial deposits Subendothelial immune
thickened BM
(Ig, C3, C4)
complex deposition

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Topics in Renal Biopsy and Pathology

V: Membranous

See membranous GN Subepithelial Ig, C3, C4 Subepithelial deposits

VI: Advanced Sclerosing

90% of glomeruli
globally sclerosed
Mesangial and
Granular IgG and C3
endothelial cell
proliferation,
thickened basement
membrane due to
extensive immune
complex deposition,
increased mesangial
matrix
Tram-track or
double-contour
appearance of
basement membrane
(best seen with silver
stain)
See MPGN Type I
C3 linear or doublecontoured along BM

Membranoproliferative
Glomerulonephritis Type I

Membranoproliferative
Glomerulonephritis Type II
(Dense Deposit Disease)
Thin Basement Membrane
Disease
Alports

Normal

Early: Normal
Late: Sclerosis
Post-Infectious
Enlarged glomeruli
Glomerulonephritis
Endocapillary
proliferation
Obliteration of
capillary loops
Increased mesangial
cells
Exudative
proliferative GN
Interstitial Nephritis
Cellular infiltrates in
interstitium
Hemolytic Uremic Syndrome Thrombosis of
glomeruli, arterioles
Nephrotic Syndrome
Minimal Change Nephrotic
Normal
Syndrome
Focal and Segmental
Glomerulosclerosis

Segmental sclerosis
of glomeruli

Membranous Nephropathy

All glomeruli
affected
Thickened capillary
walls
Membrane spikes

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Normal
Negative
Irregular granular C3,
IgG, and others

Starry sky: fine

granular C3, IgG
(early in disease)

Mesangial:
mesangial C3
(week 4-6)
Negative
Negative

Mesangial Proliferation
with immune deposits,
subendothelial electron
dense deposits between
layers of BM double
contours

Subepithelial depositsElectron dense deposits

in ribbon-like pattern
Diffuse thinning of BM
Split basement
membrane
Acute: subepithelial
humps, disappear by 6th
week
Garland type: dense
deposits along capillary
loops, subepithelial

Interrupted BM with
thickened areas
No deposits

Negative

Marked foot process

effacement

Negative (may be
positive for mesangial
C3, IgM)
Granular IgG or C3

Foot process effacement,

early hyaline deposition
Thickened basement
membrane
Electron dense
subepithelial immune
deposits
Spikes

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Renal Biopsy in the Pediatric Patient

Rapidly Progressive
Glomerulonephritis
ANCA associated vasculitis

Anti-GBM disease

Endocapillary
proliferation, some
mesangial
proliferation, urinary
space open, focal
necrosis, crescents
Proliferation of
podocytes and
epithelial cells,
proliferation of cells
around Bowmans
capsule leads to
crescent formation
Endocapillary
proliferation, some
mesangial
proliferation, urinary
space open, focal
necrosis, crescents

Negative

No deposits

Anti-glomerular
basement membrane
antibodies (IgG)
Linear pattern

No deposits

Proliferation of
podocytes and
epithelial cells,
proliferation of cells
around Bowmans
capsule leads to
crescent formation
Transplant Biopsies
Acute Cellular Rejection

Tubulitis
Endothelialitis

Humoral Rejection
Calcineurin Inhibitor Toxicity Concentric
hyalinosis
Interstitial Fibrosis

C4d positive staining

+ Arteriolar IgM

Necrosis, smooth
muscle cell injury

Table 4. Histopathology Based on Diagnosis and Type of Tissue Study

11. Conclusion
Renal biopsy in children is a safe procedure, typically performed percutaneously
with ultrasound guidance and conscious sedation, and with an 8 to 24 hour period
of post-procedure observation. Biopsy allows diagnosis of new renal conditions,
assesses health of the renal parenchyma by defining the extent of injury and potential for
recovery, and provides the pediatric clinician with valuable information to tailor
further diagnostic or therapeutic interventions. Surgical renal biopsy by open technique
or laparoscopic approach is less commonly required for the child with an isolated
renal condition. The ability to rely on percutaneous biopsy simplifies the typical
procedure, decreases patient time spent hospitalized or under supervised observation,
and ultimately provides economy of health care costs. More importantly, by allowing

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Topics in Renal Biopsy and Pathology

for precise histopathologic diagnosis rather than clinical assessment alone, the use of
renal biopsy as needed in children helps to expand the understanding of the impact
and course of certain pediatric renal diseases, their response to therapy, and their
prognosis.

12. References
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outcome of percutaneous renal biopsy in children: an analysis of 120 consecutive
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Anderson, S. E., and R. C. Whitaker. 2009. Prevalence of obesity among US preschool
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Birk, P. E., T. D. Blydt-Hansen, A. B. Dart, L. M. Kaita, C. Proulx, and G. Taylor. 2007. Low
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Broyles, S., P. T. Katzmarzyk, S. R. Srinivasan, W. Chen, C. Bouchard, D. S. Freedman, and
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Castoldi, M. C., R. M. Del Moro, M. L. D'Urbano, F. Ferrario, M. T. Porri, P. Maldifassi, G.
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33

Fowler, S. M., V. Kon, L. Ma, W. O. Richards, A. B. Fogo, and T. E. Hunley. 2009. Obesityrelated focal and segmental glomerulosclerosis: normalization of proteinuria in an
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Topics in Renal Biopsy and Pathology

Edited by Dr. Muhammed Mubarak

ISBN 978-953-51-0477-3
Hard cover, 284 pages
Publisher InTech

Published online 04, April, 2012

Published in print edition April, 2012

There is no dearth of high-quality books on renal biopsy and pathology in the market. These are either single
author or multi-author books, written by world authorities in their respective areas, mostly from the developed
world. The vast scholarly potential of authors in the developing countries remains underutilized. Most of the
books share the classical monotony of the topics or subjects covered in the book. The current book is a unique
adventure in that it bears a truly international outlook and incorporates a variety of topics, which make the
book a very interesting project. The authors of the present book hail not only from the developed world, but
also many developing countries. The authors belong not only to US but also to Europe as well as to Pakistan
and Japan. The scientific content of the book is equally varied, spanning the spectrum of technical issues of
biopsy procurement, to pathological examination, to individual disease entities, renal graft pathology,
pathophysiology of renal disorders, to practice guidelines.

How to reference

In order to correctly reference this scholarly work, feel free to copy and paste the following:
Isa F. Ashoor, Deborah R. Stein and Michael J. G. Somers (2012). Renal Biopsy in the Pediatric Patient,
Topics in Renal Biopsy and Pathology, Dr. Muhammed Mubarak (Ed.), ISBN: 978-953-51-0477-3, InTech,
Available from: http://www.intechopen.com/books/topics-in-renal-biopsy-and-pathology/pediatric-renal-biopsy

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