renal biopsy

Renal Biopsy

Mohamed Abdelhafez SolimanNephrology 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 BiopsyAssessments

1- Renal imaging

two normal size

unscarred

unobstructed

kidneys

2- Blood pressurediastolic BP<95 mm Hg

3- Urine culture

Sterile

4- Coagulation statusDrug 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.

Contraindications to Renal Biopsy

Kidney Status Patient Status

Multiple cysts

Solitary kidney

Acute pyelonephritis

Perinephric abscess

Renal neoplasm

Uncontrolled bleeding diathesis

Uncontrolled blood pressure

Uncooperative patient

Uremia

Obesity

Contraindications to Renal Biopsy

• 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 TECHNIQUEPercutaneous 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.

RENAL BIOPSY TECHNIQUE

• 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.

RENAL BIOPSY TECHNIQUE• 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 thekidney 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 needleentering 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

RENAL BIOPSY TECHNIQUE• 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 isassociated 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).

RENAL BIOPSY TECHNIQUE• 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.

RENAL BIOPSY TECHNIQUE• 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 BIOPSY TECHNIQUERenal Transplant Biopsy

• Biopsy of the transplant kidney is facilitated by the proximity of thekidney to the anterior abdominal wall and the lack of movement onrespiration.

• 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 immunohistologyshould 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 controlbleeding

0.7% 0.6%angiographic

0.1%surgical

Death 0.02%

Complications of Renal Biopsy• 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.

Complications of Renal Biopsy• 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 childrenonly if clinical features atypical of .

. minimal change disease

• Nephrotic children with atypical features :Microscopic hematuria Reduced serum complement levelsRenal impairmentFailure to respond to corticosteroids.

INDICATIONS FOR RENAL BIOPSYAcute 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 .

INDICATIONS FOR RENAL BIOPSYSystemic 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

Systemic Disease with Renal Dysfunction

• 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.

Systemic Disease with Renal Dysfunction

• Serologic testing forantineutrophil cytoplasmic antibody (ANCA) anti–glomerular basement membrane antibodies

• has allowed a confident diagnosis of renal small-vessel vasculitis orGoodpasture disease without invasive measures .

• Nonetheless, a renal biopsy should still be performed toa. confirm the diagnosis b. clarify the extent of active inflammation versus chronic fibrosis c. and thus potential for recovery

This informationimportant to decide whether to initiate or continue immunosuppressives

particularly in patients who may tolerate immunosuppression poorly.

INDICATIONS FOR RENAL BIOPSY• 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.

INDICATIONS FOR RENAL BIOPSY• 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 .

INDICATIONS FOR RENAL BIOPSY• 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 tubulointerstitialfibrosis.

• 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.

INDICATIONS FOR RENAL BIOPSY• 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 differentiatacute 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 calcineurininhibitor 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.

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renal biopsy

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