Kidney biopsy

Author: Dr Mei Zhu Peng University of California San Francisco 2008-07-28
Introduction

According the recent National Health and Nutrition Examination Surveys (NHANES III), kidney disease is on the rise in the United States (1). This trend is of concern for a number of reasons. Not only are people with kidney disease at higher risk for heart disease and cardiovascular events such as heart attacks and stroke, but many who have kidney disease are without symptoms and so are not aware that they have the disease; it is often diagnosed with routine blood and urine tests. Moreover, untreated kidney disease can progress to advanced chronic kidney disease, which requires dialysis or kidney transplantation. There are many causes of kidney disease. Diabetes and hypertension (high blood pressure) are the most common causes, but there are many other kidney diseases. Some kidney diseases can be diagnosed non-invasively from the patient’s medical history, blood and urine tests, or radiology imaging (e.g., ultrasound or computed tomography [CT] scan). Other kidney diseases can be definitively diagnosed only by examining the kidney tissue obtained through a kidney biopsy. A kidney specialist (nephrologist) will decide whether a kidney biopsy is the appropriate diagnostic tool for a particular patient. Kidney biopsies can be used for patients with acute or chronic kidney disease.

What is a kidney biopsy?

A kidney biopsy is an invasive procedure to remove a small sample of kidney tissue for diagnostic and prognostic purposes. The kidney tissue is evaluated by a pathologist (a doctor who examines human tissue samples) to make a definitive diagnosis of a particular kidney disease. Kidney biopsies can be performed on a native kidney (one of the kidneys that you are born with) or transplanted kidneys.

There are four methods for performing a kidney biopsy: percutaneous, open, laparoscopic, and transvenous. Most uncomplicated patients will have a percutaneous biopsy. The open, laparoscopic, and transvenous techniques are generally used for patients at higher risk for complications.

A percutaneous kidney biopsy involves inserting a needle through the skin and into the kidney. In the modern era, percutaneous kidney biopsies are generally performed with radiology localization (imaging) of the kidney and guidance of the biopsy needle. Using ultrasound or CT, doctors are able to see the kidney, to identify the best area of the kidney to sample, to plot the best path for the biopsy needle from the skin to the kidney, and to detect possible complications from the biopsy procedure, such as bleeding. Percutaneous biopsies are performed by radiologists and/or nephrologists.

Open kidney biopsy is a surgical procedure that exposes the kidney and allows the surgeon to obtain larger kidney samples under direct visualization. The sample is called a wedge biopsy because of the wedge-shaped sample obtained. General surgeons or urologists perform open kidney biopsies.

Laparoscopic biopsies use a specialized video camera and surgical instruments that are inserted through small skin incisions to reach the kidney. With laparoscopy, the surgeon or urologist performs the entire biopsy on video monitors.

The transvenous kidney biopsy involves inserting a catheter into a large peripheral vein (either in the groin or the neck) and advancing the catheter to the kidney. The catheter has a biopsy needle which punctures through the vein and into the kidney. The procedure is performed by interventional radiologists.

What are the indications for doing a kidney biopsy?

• Blood in the urine (also called hematuria). Blood in the urine may come from the kidney, the urinary tract (ureters, bladder, urethra), or contamination from other non-urinary sources (menstrual bleeding, gastrointestinal bleeding, or genital bleeding). Blood in the urine may not always be visible, but it can be detected with a urine test (also called a urinalysis). Blood in the urine may appear as tea or cola colored urine. Blood in the urine that originates from the kidney may be a sign of kidney inflammation called glomerulonephritis.
• Protein in the urine (also called proteinuria). Many people are not aware that they have protein in the urine. Mild proteinuria is usually diagnosed as an incidental finding during a routine urinalysis. A large amount of protein may cause urine to appear foamy in the toilet bowl or in a specimen cup. Patients with large amounts of protein in the urine may have nephrotic syndrome, a collection of signs and symptoms including protein in the urine, high cholesterol levels, low albumin levels in the blood, and edema (swelling in the legs and sometimes throughout the entire body).
• Unexplained kidney disease. The cause of kidney disease in a particular patient may not be certain from the medical history, blood tests, urine tests, and imaging of the kidney (usually ultrasound or CT scan). A kidney biopsy may help to determine the diagnosis.
• Kidney transplant rejection or failure. Kidney biopsy remains the definitive method for diagnosing kidney transplant rejection, although transplant specialists and researchers are working on less invasive methods for diagnosing kidney rejection by using blood or urine tests.
• Other diseases that can potentially involve the kidneys. Some diseases can affect multiple organ systems in the body, such as the brain, heart, lungs, kidney, and skin. Examples of systemic diseases include vasculitis and systemic lupus erythematosus (an autoimmune disease). The kidney biopsy may help diagnose the systemic disease if there is evidence of kidney involvement based on blood and urine tests. Patients with systemic lupus erythematosus can develop kidney disease. In order to see how lupus has affected the kidneys, a kidney biopsy may be necessary.
• Follow up of previously diagnosed and biopsied kidney disease. Doctors may occasionally recommend a repeat kidney biopsy to monitor the progress of the kidney disease or the response to therapy. The doctor may recommend a repeat kidney biopsy to determine whether additional or new therapy is advisable (especially if the medication has side effects and potential toxicity). For example, the nephrologist may determine that the kidney disease has progressed too much or that the disease is unlikely to respond to therapy; additional medications would expose the patient to potential toxic side effects for very little potential benefit.

How will the kidney biopsy affect the patient’s medical care?

• Determining the exact cause or diagnosis for the underlying kidney disease may alter the treatment plan or medications for the patient.
• The kidney biopsy will establish the degree and extent of damage that has already occurred, which may give the nephrologist and the patient a sense of the long term prognosis.
• If the kidney biopsy reveals transplant rejection, then the transplant specialists may recommend powerful anti-rejection medications to treat the disease.
• The kidney biopsy may help the doctor diagnose a systemic disease which is affecting the kidney and other organs in the body. The diagnosis of a systemic disease will change the overall therapy for the patient.

What are the risks of a kidney biopsy?

Overall, a kidney biopsy is a safe procedure. Like any other invasive procedure, a kidney biopsy carries certain risks, which are uncommon. The serious complications are related to bleeding in or around the kidney or into the urine. Visualization and biopsy guidance with ultrasound or computed tomography (CT) guidance reduces, but does not eliminate the risk of bleeding. A small bleed, called a hematoma, in or around the kidney is common after the procedure. A mild hematoma generally requires no specific therapy and will usually resolve on its own. If significant bleeding occurs, blood transfusions may be needed. Severe bleeding or hematomas may cause permanent damage to the kidney and loss of kidney function.

Under rare circumstances (about 1% of biopsies), an additional intervention is needed to stop excessive bleeding. Performed by interventional radiologists, angiography involves the insertion of a catheter into an artery and the injection of medication to stop the bleeding in the kidney. Angiography has generally replaced surgery as the preferred approach to treating severe complications from kidney biopsies, but surgery may be necessary in some circumstances.

The mortality rate from a kidney biopsy is about 0.1%, which means roughly 1 death in about 1000 biopsy patients (2). Death after a kidney biopsy is typically from massive hemorrhage. Visible blood in the urine is a common complication after the biopsy and may occur in about 20% of patients. Small amounts of blood in the urine or a pink discoloration to the urine are minor problems which generally resolve on their own. Large amounts of blood or blood clots in the urine can be a sign of serious bleeding which requires close monitoring. Kidney pain may also be a sign of bleeding or other serious complications. Infection of the skin at the biopsy site or kidney infections are rare since the skin incision is small and sterile technique (sterile instruments and sterile preparation of the skin) reduces the likelihood of infection.

When is a kidney biopsy not advisable?

There are circumstances when a kidney biopsy is not feasible or safe. Patients with the following conditions may not be good candidates for kidney biopsy:

• Uncontrolled high blood pressure. High blood pressures increase the risk of bleeding after the biopsy.
• Bleeding disorders. Patients with hemophilia and other bleeding disorders are at higher risk of bleeding after medical procedures.
• Low platelet count (also called thrombocytopenia). Platelets are necessary to form blood clots. A low platelet count will increase the risk of bleeding.
• Recent use of medications that increase the risk of bleeding (e.g., aspirin, warfarin, and anti-platelet agents).
• Morbid obesity. Patients with morbid obesity may require open or transvenous kidney biopsies because the kidneys are too deep for the percutaneous approach to be performed safely.
• Solitary kidney. There is a small risk of damaging the kidney during or after the biopsy. The doctor may not want to risk damaging a patient’s only working kidney. Transplant kidneys are often biopsied, but the biopsy procedure is very safe since the kidney is closer to the surface.
• Active kidney infection (pyelonephritis) or urinary tract infection.
• Pregnancy. Typically, the biopsy is postponed until after the pregnancy. Bleeding during the pregnancy could harm the mother and the fetus.
• Cancer of the kidney. Masses and tumors that appear cancerous on radiology imaging are generally removed (or resected) in their entirety using surgery, rather than biopsied. The biopsy procedure may result in tracking or spreading of the cancer along the track of the biopsy needle.
• Numerous kidney cysts. Cysts may block the approach of the biopsy needle to the non-cyst areas of the kidney. Cysts are usually diagnosed by their appearance on ultrasound or computed tomography (CT) rather than biopsy.

Preparation for a kidney biopsy

Nonsteroidal anti-inflammatory medications should be discontinued at least seven days before the procedure. Examples include aspirin, ibuprofen, and naproxen. Patients who take blood thinners (such as warfarin) or anti-platelet agents such as clopidogrel (Plavix) will need to discuss the potential risk of discontinuing these medications with their doctors. The patient’s blood count, coagulation studies, and urine tests should be within normal limits prior to doing the procedure. The blood pressure should be normal or well controlled with medications. Some doctors place an intravenous (IV) line in the patient’s vein to give medications or fluids for the procedure. Some doctors may want the patient not to eat for several hours before the procedure.

How is a kidney biopsy performed?

The most common type is a percutaneous kidney biopsy. The procedure is performed by a nephrologist and radiologist working together, although some biopsies are performed by a nephrologist or radiologist working alone. In the modern era, the percutaneous kidney biopsy is done with the aid of ultrasound or computed tomography (CT). The biopsy is performed in a medical procedure area of the hospital or the patient’s hospital room.

The procedure takes about one hour. The patient is lying face down, but is awake during the procedure because the doctor needs the patient’s cooperation. The kidneys move up and down as the patient breathes in and out, and the kidney biopsy will be timed with the patient’s breathing. The doctor may instruct the patient to breathe in or out to position the kidney in the best location for the biopsy. Biopsies in children may require the help of anesthesiologists to make the procedure safer. Conscious sedation or general anesthesia allow the doctors to perform the biopsy under controlled circumstances with close cardiac and hemodynamic monitoring of the patient.

The kidney location and biopsy approach are determined by either ultrasound or CT. The left kidney is generally chosen because its location is easier to biopsy than the right kidney. The right kidney is also near the liver, which the doctor will want to avoid during the biopsy. The biopsy site is over the lower part of the left kidney, generally in the left flank, away from the spine and below the lower ribs. The skin around the biopsy site will be cleaned with an antiseptic cleanser (e.g., iodine) and draped in sterile towels or sheets. The doctor will inject pain medication, usually lidocaine, into the skin and along the entire path the needle will travel to the kidney. The kidney is usually a few inches below the skin. A small incision is made in the skin with a scalpel to allow the biopsy needle to pass easily through the skin. The injection of pain medication and the biopsy needle are guided by either ultrasound or CT.

The biopsy needle removes a kidney sample about the thickness of spaghetti and less than an inch long. Two pieces of kidney are usually needed for the various tests the pathologist needs for a complete evaluation. Obtaining two pieces means at least two biopsy attempts. Doctors prefer to minimize the number of attempts to reduce the likelihood of bleeding and other complications. Two pieces also ensures that a representative sample of kidney is obtained, giving the pathologist reviewing the samples a good sense of what is happening in the entire kidney, especially the severity and extent of scarring throughout the kidney. One small piece of the kidney may be worse or better than the rest of the kidney, giving the pathologist an incomplete or inaccurate sense of the patient’s kidney disease or its severity.

Once the doctor has finished the biopsy procedure, the kidney may be scanned again by ultrasound or CT to look for bleeding and other complications. The doctor may apply manual pressure with his or her hands for a few minutes to prevent or control bleeding. A bandage is placed over the small skin incision, the sterile towels are removed, and the patient turns over to his or her back.

There are other methods to perform kidney biopsies. The CT-guided biopsy is very similar to the ultrasound-guided biopsy except that CT is used to visualize the kidney, the biopsy needle, and any bleeding after the biopsy. The CT approach is used when the kidneys are poorly visualized with ultrasound. In some hospitals, the CT approach is the preferred method rather than ultrasound.

The surgical approaches include open biopsy and laparoscopic biopsy. These approaches are generally used when the kidney cannot be safely biopsied with either CT or ultrasound guidance. Morbidly obese and large patients may have kidneys beyond the reach of the standard biopsy needle used for percutaneous biopsies (either CT or ultrasound guided). Doctors may decide to biopsy patients with only one functioning kidney using a surgical approach to reduce the risk of damaging the kidney (which could leave the patient without kidney function). Patients with bleeding disorders may have a surgical biopsy (either laparoscopic or open) in order to reduce the risk of bleeding after the biopsy; surgical techniques allow the surgeon to visualize the kidney and the biopsy site. The surgeon can stop any bleeding from the biopsy before finishing the procedure. The recovery time after the biopsy is typically longer with open and laparoscopic biopsies. It is unclear whether surgical techniques are safer than percutaneous biopsies, especially when one considers the additional risks of the sedation and anesthesia used in surgical biopsies.

The transvenous biopsy involves the insertion of a biopsy needle into a large vein, typically the jugular vein in the side of the neck. The biopsy needle is advanced through the patient’s veins to the kidney. The needle punctures through the wall of the vein and into the kidney tissue. Any bleeding after the biopsy will potentially drain directly into the patient’s vein, limiting blood loss. The transvenous technique may used for large or morbidly obese patients and patients with bleeding disorders. The transvenous biopsy is usually performed as an outpatient procedure; the patient typically goes home the same day after a brief observation period.

What to expect after a kidney biopsy?

After a kidney biopsy, the patient will be taken to a recovery area or hospital room where she will flat in bed on her back for several hours. This position puts pressure on the kidney, potentially preventing or controlling any bleeding from the biopsy. Bed rest will also prevent the patient from jarring the kidney and causing bleeding. Blood pressure, heart rate, and urine will be checked frequently to monitor for possible bleeding and complications. After an uncomplicated biopsy, patients may have discomfort or a mild ache around the biopsy site, especially after the local anesthetic (pain medication) has worn off. Severe pain may be a sign of bleeding or other complications. Occasionally, blood can be seen in the urine after the procedure; the patient will collect the urine so that it may be checked for bleeding.

The patient is observed for at least several hours for bleeding or other complications. Some doctors keep patients in the hospital overnight for additional observation, while other doctors discharge patients after several hours if there is no evidence of complications. The patient’s blood count is tested once or twice after the biopsy to look for evidence of bleeding. If the repeat blood tests are normal, the patient can leave the hospital. The average patient will have a small drop in the red blood cell count (hematocrit) in the complete blood count test.

What to expect after leaving the hospital

Non-steroidal anti-inflammatory medications, anti-platelet drugs, and blood thinners should be avoided for at least one to two weeks after the biopsy. Strenuous exercises (e.g., running, contact sports), heavy lifting (i.e. lifting anything greater than 15-20 lbs), and sexual intercourse should also be avoided for at least one to two weeks. Fever, redness or drainage around the biopsy site, severe pain, dizziness, lightheadedness, and visible blood in the urine should prompt the patient to seek immediate medical attention.

How long will it take to get the results of the kidney biopsy?

After the biopsy, the kidney specimen is processed by the pathology department and reviewed by the pathologist. Preliminary results from the kidney biopsy may be available within one to two days. The final results of the kidney biopsy are generally available in about 7-10 days. Typically, the biopsy sample is split into three specimens for light microscopy, immunofluorescence, and electron microscopy. The pathologist will use the information from these three methods of examining the tissue to make a final diagnosis or interpretation.

After reviewing the pathology report and/or personally examining the pathology samples with the pathologist, the nephrologist will select the appropriate treatment plan for the patient’s disease and clinical scenario. Nephrologists will occasionally treat patients based on the preliminary results alone if the kidney disease is rapidly progressive or urgent.

Rarely, the kidney biopsy fails to determine the exact cause of the kidney disease. There are two likely reasons for this. First, the doctor may not get any or enough kidney tissue for the pathologist to review. Second, the disease affecting the kidney may be patchy and involve only some areas of the kidney; consequently, the biopsy sample may not include enough tissue of the affected areas to make the diagnosis.

References

1. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of chronic kidney disease in the United States. JAMA. 2007 Nov 7;298(17):2038-47.
2. Whittier WL, Korbet SM. Timing of complications in percutaneous renal biopsy. J Am Soc Nephrol. 2004 Jan;15(1):142-7.