Renal Biopsy

A renal biopsy is used to obtain a segment of renal tissue, usually through a needle or another surgical instrument. Analysis of this tissue is then used in the diagnosis of an underlying renal condition.

In native kidneys, biopsy is used to identify various renal diseases, especially glomerular or interstitial pathologies. It can also aid in the diagnosis of renal masses and malignancies, the most common being renal cell carcinoma.

In a transplanted kidney, renal biopsy is indicated when graft dysfunction ensues with a rise in serum creatinine. Renal biopsy aids in diagnosing graft rejection and helps guide treatment, as well as the response to treatment in some cases.

 

Renal biopsy is typically performed by a radiologist under computed tomography (CT) or ultrasonographic guidance. However, a urologist can also perform a kidney biopsy during renal surgery.

There are multiple indications to perform renal biopsy, including the following:

• Unexplained renal failure

• Acute nephritic syndrome

• Nephrotic syndrome

• Isolated nonnephrotic proteinuria

• Isolated glomerular hematuria

• Renal masses (primary or secondary)

• Renal transplant rejection

• Renal transplant dysfunction

• Connective-tissue diseases (eg, systemic lupus erythematosus)

Paripovic et al[2] and Printza et al[3]  performed retrospective studies to determine indications for pediatric renal biopsy. Both found that nephrotic syndrome was the most common indication (32.9%). In the study by Paripovic et al, other indications included asymptomatic hematuria (23.4%), urinary abnormalities in systemic diseases (15.8%), and proteinuria (11.4%). Both studies found that glomerular disease was most prevalent.

According to Paripovic et al, the most common causes of glomerular disease were focal segmental glomerulosclerosis (20.9%), mesangioproliferative glomerulonephritis (14.6%), immunoglobulin A (IgA) nephropathy (8.9%), minimal change disease (13%), lupus nephritis (6%), and Henoch-Schönlein nephritis (4%).

Printza et al found that the most common findings included focal segmental glomerulosclerosis (15%), IgA nephropathy (13.5%), minimal change disease (10%), various stages of lupus nephritis (8.5%), Henoch-Schönlein nephritis (7.5%), membranous glomerulonephritis (7.5%), mesangioproliferative glomerulonephritis (6%), postinfectious glomerulonephritis (6%), hemolytic uremic syndrome (5%), tubulointerstitial nephropathies (3.5%), and acute tubular necrosis (2.5%).

The image below depicts a micrograph of focal segmental glomerulosclerosis.

Biopsy of renal transplant allograft 

A survey by the United Network for Organ Sharing (UNOS) showed great disparities in practice across US transplant centers regarding the timing and performance of surveillance kidney transplant biopsies for diagnosing subclinical graft rejection. The most common timeframe for surveillance biopsies was 3 and 12 months post-transplant. The 1- and 3-year graft survival was similar among centers performing biopsies compared with those not performing biopsies. The survey results showed the controversies around surveillance biopsies and the management of subclinical rejection.[5]

Rush et al from the Manitoba Adult Renal Transplant Program were the first to report the finding of subclinical rejection within the first 3 months after kidney transplantation.[6] Subclinical rejection can be broadly defined as lymphocytic infiltration of a renal allograft with normal function.

Rush et al further classified subclinical rejection as an increase in serum creatinine by more than 10% 2 weeks before the protocol biopsy and a histologic Banff score (a system used to score renal allograft histology; see Laboratory Medicine for more detail) of “ai2at2” (type 1A acute rejection) or greater.[7] The controversy regarding this topic is whether detecting subclinical rejection from a specific biopsy protocol can guide early successful treatment of renal allograft pathology, ultimately improving long-term graft function.

A study analyzed a 10-year follow-up of patients with subclinical rejection diagnosed at 14 days post transplantation.[8] The results showed a significant decrease in graft survival over the 10-year period, and the researchers concluded that subclinical rejection can predict transplant outcomes.

Another study attempted to determine the benefit of early detection of subclinical rejection and subsequent treatment with corticosteroids.[9] The study featured 72 patients randomized to 2 biopsy groups: one receiving biopsies at 1, 2, 3, 6, and 12 months (biopsy arm) and the other receiving biopsy at 6 and 12 months (control group). Patients in the biopsy group showed a decrease in acute rejection, reduced chronic tubulointerstitial score at 6 months, and a lower serum creatinine level at 24 months compared with patients in the control group.

On the other hand, when renal transplant dysfunction is suspected as evidenced by a rise in serum creatinine level, or clinical signs, such as fever, edema, hypertension, oliguria, and proteinuria, the allograft biopsy is mandatory for adequate histologic diagnosis.[10]  Some studies went on to analyze the accuracy of clinical prediction of allograft pathology related to diagnosis found after renal biopsy.[11] Findings revealed 43% of clinical predictions were completely correct. Of the 57% of cases in which predictions were not accurate, 26% of those cases were completely incorrect, clarifying the necessity of renal biopsy for accurate diagnosis of allograft pathology.

Renal allograft biopsy is very useful in identifying acute rejection in the transplant allograft and in guiding the treatment of antibody-mediated rejection or acute cellular rejection. Once the appropriate treatments are initiated, a repeat biopsy helps confirm adequate response to treatment.

In a high-risk transplant (ie, ABO- or human leukocyte antigen [HLA]-incompatible kidney transplants), the allograft interval biopsy schedule remains the mainstay for surveillance in this particular category of patients in whom the graft might be compromised by silent immunologic processes.[12]

Absolute contraindications to renal biopsy include the following:

• Uncorrectable bleeding diathesis

• Uncontrollable severe hypertension

• Active renal or perirenal infection

• Skin infection at biopsy site

The following are relative contraindications to renal biopsy:

• Uncooperative patient

• Anatomic abnormalities of the kidney that may increase risk

• Small kidneys

• Solitary kidney

The following factors may make renal biopsy difficult for the radiologist:

• Small kidneys

• Solitary kidney

• Retrorenal colon

• Highly vascularized tumors (increased risk of bleeding)

Other considerations include the possibility of infection, injection into a muscle (creating a hematoma), and the possibility of the biopsy needle inadvertently piercing other organs in close proximity to the kidney, such as the colon, spleen, and liver.

Preparation for kidney biopsy

Encourage patients to ask questions or raise any concerns they may have about the biopsy. Ask them to bring in a list of all their medications, including over-the-counter drugs, vitamins, and supplements. Let them know that they may need to temporarily stop taking medications that cause thinning of the blood, such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticoagulants.[13]

Recovery from kidney biopsy

Tell patients that after the biopsy they will generally have to lie on their back for 6-8 hours. Patients should expect to stay in the hospital for at least 12 hours and may have to spend the night in the hospital after the procedure. During the hospital stay, patients will receive pain medication, urine will be checked for blood, and blood tests and vital signs will be monitored.[14]

Caution patients to avoid strenuous activities, such as heavy lifting, for 2 weeks after the biopsy.

Risks of kidney biopsy

Inform patients that the most common complication is pain and bleeding at the biopsy site and that infection is rare. However, advise them to seek immediate medical attention if any of the following symptoms occur after a kidney biopsy[13] :

• Inability to urinate.
• Frequent or urgent need to urinate.
• Burning sensation during urination.
• Dark red or brown urine: Tell patients that it is normal to see some blood in the urine for up to 24 hours after the procedure.
• Blood or pus that saturates the bandage at the biopsy site.
• Worsening pain at the biopsy site.
• Fever.
• Faintness or dizziness.

Interpreting biopsy results

Let patients know that once you receive the complete biopsy results from the pathologist, you will review the results with them during a follow-up visit.

For helpful patient education resources, see the article What Is a Biopsy? and the slideshow What to Expect With a Biopsy.

Anesthesia

Percutaneous renal biopsy (PRB) is performed under local anesthesia using 1% lidocaine.

Positioning

For PRB of native kidneys, the patient is placed in the prone position, usually with a towel or pillow placed underneath the abdomen to ensure appropriate positioning.

For PRB of the transplant graft, the patient sleeps supine and the biopsy is performed in the right or left lower quadrant depending on where the kidney was transplanted.

Postprocedural care

After the physician has finished obtaining all the tissue for the biopsy, the needle is removed and pressure is applied to the biopsy site to tamponade any potential bleeding, and, finally, a bandage is applied.

The patient should typically lie supine in bed for 6-8 hours immediately after the procedure. In total the patient should expect to stay in the hospital for at least 12 hours and may have to spend one night in the hospital after the procedure. During this time, the patient will be given proper pain medication, urine will be checked for blood, and blood counts and vital signs will be monitored throughout the patient’s stay in the hospital.[14]

Complications

The most common complication of renal biopsy is pain and bleeding at the biopsy site.

Bleeding may occur in 3 distinct locations within the kidney: into the collecting system, under the renal capsule, or into the perinephric space. If the bleeding enters the collecting system, blood is seen in the urine and can cause pain and obstruction. If the bleeding is subcapsular, it can create enough of a mechanical compressive effect onto the kidney to cause hypertension owing to an increase in the release of renin, which is a hormone that is secreted by the juxtaglomerular apparatus of the kidney in the proximal convoluted tubule to increase systemic blood pressure.[4]

Subcapsular hematomas in transplanted kidneys are worrisome, and one should make sure that kidney perfusion is not compromised by the compression effect that might cause graft thrombosis and loss.

The injured kidney can also undergo fibrosis and, ultimately, chronic hypertension and perhaps even renal failure can result if the contralateral kidney is compromised. This phenomenon is known as the Page kidney effect after Dr Irvine Page, who first demonstrated in 1939 that wrapping cellophane tightly around animal kidneys can cause hypertension.[15] Perinephric bleeding can ultimately cause hemodynamic instability as it continues to pool in the retroperitoneal space, necessitating blood transfusion.

Another known complication of a renal biopsy is the development of an arteriovenous fistula. Up to 18% of patients undergoing renal biopsy may develop this complication.[16] However, in most cases, the arteriovenous fistula is asymptomatic and heals before causing symptoms. Nonetheless, some patients may experience symptoms such as hematuria, hypertension, and renal insufficiency. It is important to treat symptomatic fistulas as soon as possible to prevent further deterioration. Treatment consists of selective angioembolization performed by a vascular interventional radiologist to halt the bleeding.[16]

The image below depicts perinephric hematoma after renal biopsy.

A native renal biopsy is typically performed percutaneously through the patient’s back. Other possible approaches are the transjugular kidney biopsy and laparoscopic/open kidney biopsy. For kidney transplant, the graft biopsy is percutaneous and ultrasound guided.

Percutaneous renal biopsy

The percutaneous renal biopsy (PRB) is the standard of care. It is most commonly performed by radiologists and nephrologists.[17]

Adequate tissue is obtained in 95-99% of PRBs, with a typical yield of about 10-20 glomeruli on average, depending on the type of disease, when using 14- and 16-gauge needles.

The patient is placed in the prone position, and the biopsy is typically taken from the lower pole of the kidney if there are no specific locations of interest. In order to localize this portion of the kidney, the biopsy is typically performed under ultrasound guidance.[18]

The biopsy needle is guided using ultrasound to ensure visualization of the needle as it pierces the kidney parenchyma. The size of the needle varies based on physician preference. Needle sizes may vary from 14-18 gauge. Care is taken not to enter the collecting system (as it would result in hematuria) or to go near the renal hilum (to prevent injury to the vessels). An illustration of ultrasound-guided percutaneous renal biopsy is depicted below.

A study by Kriegshauser et al found that operator experience, taking more than 1 specimen, and the use of the cortical tangential approach significantly improved the pathologic material obtained during native renal biopsies.[19]

In obese patients and in patients with complex kidney anatomy (eg, horseshoe kidney), renal biopsy can be performed with computed tomography (CT) guidance (see image below). CT scanning can also be used for renal biopsy whenever ultrasound cannot identify or visualize the kidney or the needle biopsy.

If no imaging is used to guide the biopsy, the patient may be asked to take several deep breaths to ensure proper needle placement before obtaining the biopsy.

Transjugular kidney biopsy

Initially performed in the 1990s, the transjugular kidney biopsy is most commonly performed for patients requiring a simultaneous liver/kidney biopsy. Some case series showed no difference in the diagnostic yield or the complication rate compared with PRB. Potential complications are contrast-induced nephropathy as well as capsular perforation that could require coil embolization.[20]  

Surgical biopsy

Laparoscopic kidney biopsy, performed by urologists, can be the best approach in cases of morbidly obese patients, failed attempts at PRB, severe coagulopathy, a solitary kidney, or very complex anatomy. The major advantages are direct visualization and a biopsy of the kidney with good hemostatic control of the biopsy site. The biopsy material is usually abundant and sufficient to make the diagnosis of the underlying condition.[21]

Perioperative renal biopsy

In some cases, a urologist may obtain a piece of renal tissue to determine whether it is benign or malignant or to determine whether the margins of resection are negative. For instance, a urologist performing a partial nephrectomy may take a renal biopsy at the surgical bed to ensure that no tumor is left behind before continuing with the renorrhaphy. This can be approached in the same manner as the partial nephrectomy—robotic, purely laparoscopic, or the traditional open approach.

The Banff grading system for renal biopsy of transplant allograft

The goal of the Banff process is integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus-based reporting system that offers precise composite scores and accurate routine diagnostics of allograft dysfunction and rejection.

The mainstay for interpretation of biopsy results from renal transplant allograft is based on the Banff grading system. This grading system allocates a score from 0 to 3 to each element analyzed by the pathologies: ie, hyaline arteriolar thickening, arteriolar hyalinosis, cg (glomerular double contours), ci (interstitial fibrosis), ct (tubular atrophy), i (inflammation), i-IFTA (interstitial inflammation in areas of interstitial fibrosis and tubular atrophy), mm (mesangial matrix expansion), ptc (peritubular capillaritis), PTC (peritubular capillary), t (tubulitis), v (intimal arteritis), and C4d (complement activation) scores.[22]