Renal biopsy

Renal Biopsy
Mohamed Abdelhafez Soliman
Nephrology Specialist
NMGH

Renal Biopsy
 Introduction
 Is Renal Biopsy A Necessary Investigation?
 Biopsy adequacy
 Workup For Renal Biopsy
 Contraindications To Renal Biopsy
 Renal Biopsy Technique
 Post Biopsy Monitoring
 Complications Of Renal Biopsy
 Indications For Renal Biopsy

INTRODUCTION
• Percutaneous renal biopsy was first described in the early 1950s .
• These early biopsies were performed with the patient in sitting position by
use of a suction needle and intravenous urography for guidance.
• An adequate tissue diagnosis was achieved in less than 40% of these early cases.
• In 1954, Kark described a modified technique using the Franklin modified Vim-
Silverman needle, with the patient in a prone position and an exploring needle
used to localize the kidney before insertion of the biopsy needle.
• These modifications yielded a tissue diagnosis in 96% of cases, and no major
complications were reported.

INTRODUCTION
• Since then, the basic renal biopsy procedure has remained largely
unchanged, although the use of real-time ultrasound and refinement of
biopsy needle design have offered significant improvements.
• Renal biopsy is now able to provide a tissue diagnosis in more than 95% of
patients, with a life-threatening complication rate of less than 0.1%.

Is Renal Biopsy a Necessary Investigation?
• Early studies suggested that renal biopsy provided
diagnostic clarity in majority of patients , but this
information did not alter management, with the exception
of those with heavy proteinuria or systemic disease.
• More recent prospective studies suggest that :
Renal biopsy identifies a diagnosis different from that
predicted on clinical grounds in 50% to 60% of patients
and leads to a treatment change in 20% to 50%.
• This is apparent in patients with heavy proteinuria or AKI,
more than 80% of whom have biopsy findings that alter
their management.

Biopsy Adequacy
• The number of glomeruli in the sample is the
major determinant of whether the biopsy will be
diagnostically informative.
• A typical diagnostically useful biopsy sample will
contain 10 to 15 glomeruli .
• Because of sampling issue, a biopsy sample of
this size will be unable to diagnose focal diseases
and at best will provide imprecise guidance on
the extent of glomerular involvement.

Biopsy Adequacy
• An adequate biopsy should provide samples for :
immunohistology and electron microscopy (EM).
• Immunohistology is provided by either immunofluorescence on
frozen material or immunoperoxidase on fixed tissue, according to
local protocols .
• It is helpful for the biopsy cores to be viewed immediately after
being taken under microscope to ensure that they contain cortex
and when cores are divided, immunohistology and EM samples
both contain glomeruli.

Biopsy Adequacy
• If the material obtained for a pathologic evaluation is
insufficient, a discussion with pathologist should address
how best to proceed before the tissue is placed in fixative .
• So that provide maximum information for specific clinical
scenario.
• For example, if patient has heavy proteinuria, most information
will be gained from EM because it is able to demonstrate
Podocyte foot process effacement
Focal sclerosis
Electron-dense deposits of immune complexes.
. Organized deposits of amyloid.

Workup for Renal Biopsy
Assessments
1- Renal imaging
two normal size
unscarred
unobstructed
kidneys
2- Blood pressure
diastolic BP
<95 mm Hg
3- Urine culture
Sterile
4- Coagulation status
Drug therapy stop aspirin, clopidogrel, and warfarin 7 days before biopsy
NSAIDs and S.C heparin 24 hours before biopsy.
Platelet count >1003/l
Prothrombin time <1.2 times control
Activated partial thromboplastin time (APTT) <1.2 times control
Bleeding time <10 min (measure if BUN >56 mg/dl and high risk)
(if prolonged, give DDAVP 0.4 u g/kg 2–3 h before biopsy)

Contraindications to Renal Biopsy
 bleeding diathesis is the major contraindication .
 If the disorder cannot be corrected and the biopsy is indispensable
.Alternative approaches can be used, such as open biopsy,
laparoscopic biopsy or transvenous (usually transjugular) biopsy .
 Inability of the patient to comply with instructions during renal
biopsy is another major contraindication.
 Sedation or in extreme cases general anesthesia may be necessary.
 Relative contraindications to renal biopsy are Hypertension
(>160/95 mm Hg), hypotension, perinephric abscess,
pyelonephritis, hydronephrosis, severe anemia, large renal tumors,
and cysts.
 When possible, these should be corrected before the biopsy is
undertaken.

Kidney Status Patient Status
Multiple cysts
Solitary kidney
Acute pyelonephritis
Perinephric abscess
Renal neoplasm
Uncontrolled bleeding diathesis
Uncontrolled blood pressure
Uncooperative patient
Uremia
Obesity

• The solitary functioning kidney has been considered
a contraindication to percutaneous biopsy, and risk
of biopsy is reduced by direct visualization at open
biopsy.
• However, the post biopsy nephrectomy rate of
1/2000 to 1/5000 is comparable to the mortality rate
associated with the general anesthetic required for
an open procedure.
• Therefore, in the absence of risk factors for bleeding,
percutaneous biopsy of a solitary functioning kidney
can be justified.

RENAL BIOPSY TECHNIQUE
Percutaneous native Renal Biopsy
• Biopsy is performed by nephrologists with
continuous (real-time) ultrasound guidance and
disposable automated biopsy needles.
• We use 16-gauge needles and the trend toward
fewer bleeding complications of smaller needles.
• For most patients, premedication or sedation is not
required.
• The patient is prone, and a pillow is placed under
the abdomen at the level of the umbilicus to
straighten the lumbar spine and to splint the
kidneys.

• Ultrasound is used to localize the lower pole of
the kidney where the biopsy will be performed
(usually the left kidney).
• A pen mark is used to indicate the point of entry
of the biopsy needle.
• The skin is sterilized with povidone-iodine
(Betadine) . A sterile fenestrated sheet is placed
over the area to maintain a sterile field.
• Local anesthetic (2% lidocaine ) is infiltrated into
the skin at the point previously marked.

Renal biopsy procedure
• The biopsy needle is introduced at an angle of
approximately 70 degrees to the skin and is guided by
continuous ultrasound.
• The operator is shown wearing a surgical gown.

• While the anesthetic takes effect, the ultrasound probe is covered
in a sterile sheath. Sterile ultrasound jelly is applied to the skin
• Under ultrasound guidance, a 10-cm, needle is guided to the renal
capsule.
• A stab incision is made through the dermis to ease passage of
the biopsy needle. This is passed under ultrasound guidance to the
kidney capsule .
• As the needle approaches the capsule, the patient is instructed to take a
breath until the kidney is moved to a position such that the lower pole
rests just under the biopsy needle, and then to stop breathing.
• The biopsy needle tip is advanced to the renal capsule, and the trigger
mechanism is released, firing the needle into the kidney .
• The needle is immediately withdrawn, the patient is asked to resume
breathing, and the contents of the needle are examined .

Renal biopsy imaging. Ultrasound scan
shows the needle
entering the lower pole of the left
kidney. Arrows indicate the needle track,
which appears as a fuzzy white line.
Renal biopsy imaging
CT left kidney
The angle of approach of
needle is demonstrated.
Note adjacency to
the lower pole of the
kidney

• We examined the tissue core under an operating
microscope to ensure that renal cortex has been
obtained .
• A second pass of the needle is usually necessary to
obtain additional tissue for immunohistology and EM.
• If insufficient tissue is obtained, further passes of the
needle are made.
• However, passing the needle more than four times is
associated with a modest increase in the post biopsy
. complication rate.
• Once sufficient renal tissue has been obtained, the
skin incision is dressed and the patient rolled directly
into bed for observation.

• A core of renal tissue is demonstrated
in the sampling notch of the biopsy needle

Renal biopsy micrographs
• Appearance of renal biopsy material under the operating
microscope.
A Low-power view shows two good-sized cores.
B Higher-magnification view shows typical appearance
of glomeruli (arrows).

• No single fixative developed that allows good-quality light
microscopy, immunofluorescence, and EM to performed on
same sample.
• Therefore, renal tissue is divided into three samples
and placed in
# Formalin for light microscopy
# Normal saline for immunofluorescence
# Glutaraldehyde for EM
• Some centers are able to produce satisfactory light
microscopy, immunohistochemistry, and EM on
formalin-fixed biopsy material, this depends on the
expertise of individual laboratories.

• For obese patients and patients with respiratory conditions who
find the prone position difficult, supine anterolateral approach
has recently described.
• Patients lie supine with the flank on the side to be sampled
elevated by 30 degrees with towels under the shoulder and
buttocks. The biopsy needle is inserted through the Petit (inferior
lumbar) triangle, bounded by the latissimus dorsi muscle, 12th
rib, and iliac crest.
• This technique provides good access to the lower pole of the
kidney, is better tolerated than the prone position by these
patients .

Renal Transplant Biopsy
• Biopsy of the transplant kidney is facilitated by the proximity of the
kidney to the anterior abdominal wall and the lack of movement on
respiration.
• It is performed under real-time ultrasound guidance with use of an
automated biopsy needle.
 In most patients, renal transplant biopsy is performed to identify
cause of acute allograft dysfunction (acute rejection), therefore
diagnosis can be made on a formalin fixed sample alone for light
microscopy.
 If vascular rejection is suspected, a snap-frozen sample for C4d
immunostaining should also be obtained (although some laboratories
are able to detect C4d onformalin-fixed material).
 If recurrent or de novo GN is suspected in patients with chronic
allograft dysfunction, additional samples for EM and immunohistology
should be collected.

Post biopsy Monitoring
• After the biopsy, the patient is placed supine and
subjected to strict bed rest for 6 to 8hours.
• The blood pressure is monitored frequently
• urine examined for visible hematuria
• and the skin puncture site examined for excessive
bleeding.
• If there is no evidence of bleeding after 6 hours, the
patient is sat up in bed and subsequently allowed
to move.
• If visible hematuria develops, bed rest is continued
until the bleeding settles.

Post biopsy Monitoring
• Outpatient (day-case) renal biopsy with same-day discharge after
6 to 8 hours of observation has become increasingly popular for
both native and renal transplant biopsies.
• This justified by that significant complications of renal biopsy will
become apparent during this shortened period of observation.
• outpatient renal biopsy is acceptably safe when a low-risk patient
group is selected.
• This view has been challenged by a study of 750 native renal
biopsies, which showed that only 67% of major complications, as
required a blood transfusion or invasive procedure or resulted in
urinary tract obstruction, septicemia, or death, were apparent by
8 hours after biopsy.
• These authors concluded that a 24-hour observation period is
preferable.

Complications of Renal Biopsy
Complication Percentage
Visible hematuria 3.5%
Need for blood transfusion 0.9%
Need for intervention to control
bleeding
0.7% 0.6%angiographic
0.1%surgical
Death 0.02%

• Dull ache Pain around the needle entry site when the local anesthetic
wears off after renal biopsy.
 Simple analgesia with paracetamol usually suffices.
• More severe pain in the loin or abdomen on the side of the biopsy
suggests significant perirenal hemorrhage.
• The mean decrease in hemoglobin after a biopsy is approximately 1 g/dl.
• Significant perirenal hematomas are almost associated with severe loin
pain.
• Both visible hematuria and painful hematoma are seen in 3% to 4% of
patients after biopsy.
 The initial management is strict bed rest and maintenance of normal
coagulation indices.
• If bleeding is brisk and associated with hypotension or prolonged and
fails to settle with bed rest, renal angiography should performed to
identify source of bleeding. Coil embolization can performed, and this
eliminate need for open surgical intervention and nephrectomy.

• Most postbiopsy arteriovenous fistulas detected by Doppler
• Ultrasound or contrast-enhanced C T , can be found as many as
18% of patients.
• Because most are clinically silent and more than 95% resolve
spontaneously within 2 year .
• In a small minority of patients, arteriovenous fistulas can lead to
visible hematuria (typically recurrent, dark red, and often with
blood clots), hypertension, and renal impairment, which requires
embolization.
• Death resulting directly from renal biopsy become much less
common according to recent biopsy series compared with earlier
reports.
• Most deaths result from uncontrolled hemorrhage in
high-risk patients, particularly those with severe renal impairment.

INDICATIONS FOR RENAL BIOPSY
• Ideally, analysis of a renal biopsy sample
should identify :
 a specific diagnosis .
 reflect the level of disease activity .
 provide information to allow decisions,
. planned treatment .
• Although renal biopsy not always able to fulfill
these criteria .
• It remains a valuable clinical tool and of
particular benefit in the clinical situations .

• Nephrotic Syndrome
• Acute Kidney Injury
• Systemic Disease with Renal Dysfunction
• Non-nephrotic Proteinuria
• Isolated Microscopic Hematuria
• Unexplained Chronic Kidney Disease
• Familial Renal Disease
• Renal Transplant Dysfunction

Nephrotic Syndrome
1- Routinely indicated in adults .
2- In prepubertal children
only if clinical features atypical of .
. minimal change disease
• Nephrotic children with atypical features :
Microscopic hematuria
Reduced serum complement levels
Renal impairment
Failure to respond to corticosteroids.

Acute Kidney Injury
Obstruction
Reduced renal perfusion
Acute tubular necrosis have been ruled out
• In a minority of patients, a confident diagnosis
cannot be made .
• Renal biopsy should be performed on an urgent
basis so that appropriate treatment started before
irreversible renal injury develops.
• This is particularly true in patients with AKI
accompanied by active urine sediment .

Systemic Disease with Renal Dysfunction
• In patients with
1 Small-vessel vasculitis
2 Anti–glomerular basement membrane disease
3 Systemic lupus
• In patients with diabetes only if atypical features
present

• Patients with diabetes mellitus and renal dysfunction do
not usually require biopsy if diabetic nephropathy
associated with
Isolated proteinuria
Diabetes of long duration
Evidence of other micro vascular complications.
• Renal biopsy should be performed if the presentation is atypical
Proteinuria associated with glomerular hematuria (acanthocytes)
Absence of retinopathy or neuropathy (in patients type 1 DM)
Onset of proteinuria < 5 years from documented onset of DM
Presence of immunologic abnormalities.

• Serologic testing for
antineutrophil cytoplasmic antibody (ANCA)
anti–glomerular basement membrane antibodies
• has allowed a confident diagnosis of renal small-vessel vasculitis or
Goodpasture disease without invasive measures .
• Nonetheless, a renal biopsy should still be performed to
a. confirm the diagnosis
b. clarify the extent of active inflammation versus chronic fibrosis
c. and thus potential for recovery
This information
important to decide whether to initiate or continue immunosuppressives
particularly in patients who may tolerate immunosuppression poorly.

• Non-nephrotic Proteinuria May be indicated if proteinuria >1 g/24 h
• The value of renal biopsy in patients is debatable.
• All conditions that result in nephrotic syndrome
can cause non-nephrotic proteinuria, except MCD.
• In patients with proteinuria of more than 1 g/day, treatment with strict
blood pressure control and (ACE) inhibitors or (ARBs) reduces proteinuria
and reduces the risk for progressive renal dysfunction .
• Although renal biopsy may not lead to an immediate change in
management : it can be justified because it will provide
- prognostic information
- identify a disease for which therapeutic approach is indicated
- provide clinically important information about the future risk of .
.disease recurrence after renal transplantation.

• Isolated Microhematuria Indicated only in unusual circumstances
• Patients initially evaluated to identify structural lesions as renal
stones or renal and urothelial malignant neoplasms if older than
40 y.
• The absence of a structural lesion suggests that hematuria have
a glomerular source.
• Biopsy studies identified glomerular lesions in up to 75% of
biopsies.
• IgA nephropathy is the most common lesion, followed by
thin basement membrane .
• In the absence of nephrotic proteinuria, renal impairment, or
hypertension, the prognosis is excellent .
• because no specific therapies are available, renal biopsy is not
necessary and patients require only follow-up.

• Biopsy should be performed only :
 if the result would provide reassurance to a patient .
 avoid repeated urologic investigations .
 or provide specific information :
i. in evaluation of potential living kidney donors .
ii. in familial hematuria .
iii. or for life insurance and employment purposes .

• Unexplained Chronic Kidney Disease
• Renal biopsy can be informative in the patient with
unexplained CKD and normal-sized kidneys .
• Studies shown that in these patients with CKD, the biopsy will
demonstrate disease that was not predicted in almost half.
• However, if both kidneys are small (<9 cm on ultrasound), the
risks of biopsy are increased, and the diagnostic information.
limited by extensive glomerulosclerosis and tubulointerstitial
fibrosis.
• However, immunofluorescence studies may still be informative :
For example, glomerular IgA deposition may be identified . .
. despite advanced structural damage.

• Familial Renal Disease
• A renal biopsy performed in one affected family member
may secure the diagnosis for the whole family and avoid
the need for repeat investigation.
• Conversely, a renal biopsy may unexpectedly
identify disease that has an inherited basis,
thereby stimulating evaluation of other family
members.

• Renal Transplant Dysfunction
• Renal allograft dysfunction in the absence of ureteral obstruction, urinary
sepsis, renal artery stenosis, or toxic levels of calcineurin inhibitors requires
a renal biopsy to determine the cause.
 In the early post-transplantation period, this is most useful in differentiat
acute rejection from ATN and increasingly prevalent BK virus nephropathy.
 Later , renal biopsy can differentiate late acute rejection from chronic allograft
nephropathy , recurrent or de novo glomerulonephritis (GN) , and calcineurin
inhibitor toxicity.
• The accessible location of the renal transplant in the iliac fossa facilitates
biopsy of the allograft and allows repeated biopsies when indicated.
• This encouraged many units to adopt a policy of protocol biopsies to detect
subclinical acute rejection and renal scarring and to guide the choice of
immunosuppressive therapy .

Role of Repeat Renal Biopsy
• In some patients, a repeat biopsy may be indicated.
• The pathologic changes in lupus nephritis may evolve,
necessitating treatment adjustment.
• Corticosteroid-resistant/dependent MCD or frequently
relapsing MCD may actually represent a missed diagnosis
of focal segmental glomerulosclerosis (FSGS), which may
be detected on repeat biopsy.

Renal biopsy

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