If you have received a kidney transplant, your doctor may order one or more biopsies of the transplanted kidney over the course of your care. Receiving a biopsy report can feel confusing and worrying, especially when the language is unfamiliar. This article explains what a kidney transplant biopsy is, why it is done, what your report contains, and what the most common findings mean.
What is a kidney transplant biopsy?
A kidney transplant biopsy is a procedure in which a small piece of tissue is removed from your transplanted kidney and examined under a microscope by a pathologist. A pathologist is a doctor who specializes in diagnosing disease by studying tissue.
The biopsy is usually done using a thin needle that is guided through the skin into the transplanted kidney, which is typically located in the lower abdomen near the pelvis. The procedure is usually performed under ultrasound guidance to ensure the needle goes to the right place. Most patients experience mild discomfort but are awake during the procedure.
Why is a kidney transplant biopsy done?
Your transplant team may order a biopsy for several reasons:
- To investigate a decline in kidney function. If blood tests show that your transplanted kidney is not working as well as expected, a biopsy can help determine why.
- To check for rejection. The immune system may recognize the transplanted kidney as foreign and try to attack it. A biopsy can show whether this is happening and how severe it is.
- To look for other causes of kidney injury. Sometimes, kidney function declines for reasons other than rejection, such as infection, medication effects, or a recurrence of disease in the transplanted kidney.
- As a routine surveillance biopsy. Some transplant programs perform scheduled biopsies at set intervals after the transplant, even when kidney function appears normal, to look for early, silent injury that may not yet be causing symptoms.
What does the pathology lab do with the biopsy tissue?
After the biopsy needle is removed, the small core of tissue is sent to the pathology laboratory. Because kidney disease is complex, transplant kidney biopsies are examined using three different types of microscopy, each of which reveals different information:
- Light microscopy. The tissue is sliced very thinly, placed on glass slides, and stained with special dyes. This allows the pathologist to examine the structure of the kidney under a standard microscope, looking for inflammation, scarring, and damage.
- Immunofluorescence microscopy. A separate piece of tissue is frozen and examined using antibodies tagged with fluorescent dyes. This technique detects immune molecules, such as antibodies and complement proteins, that may have deposited inside the kidney. The pattern and location of these deposits help identify specific diseases.
- Electron microscopy. A very thin slice of tissue is examined with an electron microscope, which can show structures far too small to see with a regular microscope. This is particularly useful for detecting tiny immune deposits and assessing the fine structure of the kidney’s filtering units.
Not every biopsy requires all three microscopy techniques. Your pathologist will decide which tests are needed based on the initial findings.
What are the main parts of a kidney transplant biopsy report?
A transplant kidney biopsy report is more detailed than most pathology reports because it must carefully evaluate multiple parts of the kidney and score the findings using a standardized system called the Banff classification. Your report will typically include the following:
Adequacy of the biopsy
The first thing the pathologist reports is whether the biopsy contained enough tissue to make a reliable assessment. A satisfactory biopsy for most purposes requires at least seven glomeruli and at least one artery. If the sample was too small, the report may say the biopsy is “inadequate” or “insufficient for full assessment,” which may mean another biopsy is needed.
The Banff classification
The Banff classification is an internationally agreed-upon system that pathologists use to describe and grade the findings in a transplant kidney biopsy. It was first developed in Banff, Canada, and is updated regularly as new research emerges. The Banff system provides a standardized language so that transplant centers around the world can communicate consistently about biopsy findings.
The Banff classification organizes findings into several diagnostic categories:
- Normal or non-specific changes. No significant abnormality is identified, or only minor non-specific changes are present that do not indicate rejection or active disease. If your report falls into this category, it is reassuring news, although your transplant team will continue to monitor your kidney function closely.
- Antibody-mediated rejection (ABMR). Damage caused by antibodies produced by the immune system that specifically target the transplanted kidney. These antibodies injure the tiny blood vessels inside the kidney. Antibody-mediated rejection can be acute (occurring suddenly) or chronic (developing slowly over months to years).
- Suspicious for rejection. Some features of rejection are present, but not enough to meet the full criteria for a definitive diagnosis. Your transplant team may recommend closer monitoring, additional blood tests, or a repeat biopsy.
- T cell-mediated rejection (TCMR). Damage caused directly by immune cells called T cells that enter the kidney and attack its tubules and supporting tissue. Like antibody-mediated rejection, T cell-mediated rejection can be acute or chronic, and both can occur simultaneously.
- Interstitial fibrosis and tubular atrophy (IFTA). Scarring of the kidney tissue without a specific active cause identified at the time of the biopsy. IFTA represents the permanent result of past or ongoing injury and is one of the most common findings on surveillance biopsies. The amount of scarring is reported as a percentage and graded from mild to severe.
- Other diagnoses. Findings that do not fit the rejection categories above. This includes conditions such as BK virus infection, recurrence of the disease that originally damaged your kidneys, injury from immunosuppressive medications, or other forms of kidney disease that can develop after transplant. These are described in detail later in this article.
More than one category can appear in the same biopsy. For example, a report may describe both T cell-mediated rejection and interstitial fibrosis and tubular atrophy, indicating active rejection and evidence of prior scarring. Your transplant team will explain which findings are most important for your care.
What are the most common findings in a transplant kidney biopsy report?
The following are the findings most commonly described in transplant kidney biopsy reports. Your report may include some or all of these terms.
Glomeruli (the filtering units)
The glomeruli are the tiny filtering units of the kidney. Each kidney contains millions of them, and a transplant biopsy typically contains between 7 and 30 glomeruli. The pathologist examines these carefully for:
- Glomerulitis. Inflammation inside the glomeruli, in which immune cells are found within the tiny capillaries of the filtering unit. Glomerulitis is one of the features used to identify antibody-mediated rejection.
- Glomerulosclerosis. Scarring of the glomeruli. Some scarring is expected as the kidney ages, but excessive scarring indicates prior or ongoing injury. When the whole glomerulus is scarred, it is called global glomerulosclerosis. When only part of the kidney is scarred, it is called segmental glomerulosclerosis.
- Thrombotic microangiopathy (TMA). Small clots or signs of blood vessel damage inside the glomeruli. TMA can result from antibody-mediated rejection, certain medications, or other conditions.
- Recurrent or de novo glomerulonephritis. Occasionally, the disease that originally damaged the native kidneys can recur in the transplanted kidney, or a new kidney disease can develop. The biopsy can identify these conditions.
Tubules (the drainage tubes)
The tubules are tiny tube-shaped structures that carry filtered fluid away from the glomeruli and help produce urine. The pathologist looks for:
- Tubulitis. Inflammation inside the tubule walls, in which immune cells are found within the tubule lining. Tubulitis is a key feature of T cell-mediated rejection. The severity is scored from t1 (mild) to t3 (severe) based on how many immune cells are found per tubule.
- Tubular injury. Damage to the cells lining the tubules, which can occur with rejection, reduced blood flow, or medication toxicity.
- Tubular atrophy. Shrinkage and loss of normal tubular structure indicate chronic damage. It is reported as a percentage of the tubules affected: minimal (less than 10%), mild (10–25%), moderate (26–50%), or severe (more than 50%).
Interstitium (the supporting tissue)
The interstitium is the connective tissue that surrounds and supports the tubules, blood vessels, and glomeruli. The pathologist looks for:
- Interstitial inflammation. Infiltration of immune cells into the interstitium. This is a key feature of T cell-mediated rejection and is scored from i1 (10–25% of the tissue involved) to i3 (more than 50% involved).
- Interstitial fibrosis. Scarring of the interstitium, indicating chronic damage. Like tubular atrophy, it is reported as a percentage and graded as minimal, mild, moderate, or severe.
Interstitial fibrosis and tubular atrophy (IFTA) are often reported together because they tend to occur together and together reflect the degree of chronic, irreversible injury in the kidney.
Blood vessels (arteries and capillaries)
The blood vessels in the transplanted kidney are carefully examined because they are a critical target of both rejection and chronic injury.
- Intimal arteritis (endothelialitis). Inflammation beneath the inner lining of the arteries. This is a hallmark of moderate to severe T cell-mediated rejection and is scored from v1 (mild, affecting less than 25% of the vessel wall) to v3 (severe, with transmural inflammation or arterial necrosis).
- Peritubular capillaritis. Inflammation in the tiny capillaries that run alongside the tubules. This is one of the key features used to diagnose antibody-mediated rejection and is scored from ptc1 to ptc3.
- Arteriolar hyalinosis. Thickening of the walls of small arteries with a glassy material called hyalin. This can result from long-standing high blood pressure, diabetes, or the effects of certain immunosuppressive medications, particularly calcineurin inhibitors such as tacrolimus.
- Arterial sclerosis. Thickening and stiffening of larger artery walls due to chronic injury. This reduces blood flow to the kidney and contributes to progressive loss of function over time.
C4d staining
C4d is a protein that is deposited in the walls of the peritubular capillaries when antibodies activate the complement system, a part of the immune response. Positive C4d staining in the peritubular capillaries is a marker of antibody-mediated rejection, although its absence does not rule out this diagnosis. C4d is detected by immunofluorescence and is reported as negative, focal positive (fewer than 50% of capillaries staining), or diffuse positive (50% or more staining).
Donor-specific antibodies (DSAs)
Your pathology report may reference donor-specific antibodies (DSAs). These are antibodies in your blood that specifically target proteins on the cells of the transplanted kidney. DSAs are not detected in the biopsy itself but are measured in blood tests and are an important part of the diagnosis of antibody-mediated rejection. Your transplant team will consider your DSA results alongside your biopsy findings when making treatment decisions.
What is the difference between acute rejection and chronic rejection?
Rejection can occur at different stages after transplant and in different ways:
- Acute rejection occurs suddenly and involves active inflammation and immune attack. It can often be treated effectively if identified early, usually by adjusting immunosuppressive medications.
- Chronic rejection develops gradually over months to years and results in progressive scarring and loss of kidney function. It is more difficult to treat and may not respond as well to changes in medication.
Both T cell- and antibody-mediated rejection can be acute or chronic, and both can occur simultaneously.
What does it mean if my report mentions calcineurin inhibitor toxicity?
Calcineurin inhibitors, such as tacrolimus (Prograf) and cyclosporine, are immunosuppressive medications that most transplant recipients take to prevent rejection. While these medications are essential for protecting the transplanted kidney from the immune system, they can also cause their own form of kidney damage when levels are too high or are used for many years.
In the biopsy, calcineurin inhibitor toxicity typically appears as arteriolar hyalinosis (described above) and, in more severe cases, patchy scarring of the kidney. Your transplant team will consider the biopsy findings alongside your drug levels and blood tests to decide whether your medication doses need adjusting.
What does it mean if my report mentions BK virus or polyomavirus nephropathy?
BK virus is a common virus that most people carry harmlessly. In transplant recipients, however, the immune suppression needed to prevent rejection can allow BK virus to reactivate and infect the transplanted kidney. This condition is called polyomavirus-associated nephropathy (PVAN), sometimes written as BK nephropathy.
The biopsy can identify viral inclusions (abnormal structures inside kidney cells that indicate infection) and confirm the diagnosis with a special stain called SV40 immunostaining. Your transplant team will typically reduce the dose of immunosuppressive medication to allow your immune system to control the infection, while being careful not to increase the risk of rejection.
For more information, see our article on Polyomavirus nephropathy (BK nephropathy).
What does it mean if my report mentions recurrent disease?
Some kidney diseases that originally caused your kidneys to fail can come back in a transplanted kidney. This is called recurrent disease. Common examples include focal segmental glomerulosclerosis (FSGS), IgA nephropathy, and membranous glomerulonephritis. The pathologist identifies recurrent disease based on the pattern of injury seen on light microscopy, immunofluorescence, and electron microscopy. If recurrent disease is found, your transplant team may adjust your treatment or monitor you more closely.
What does the biopsy report mean for my transplanted kidney’s future?
A single biopsy result is one piece of information in a much larger picture. Your transplant team uses the biopsy findings, along with your blood and urine tests, medication levels, clinical history, and symptoms, to understand what is happening and what to do next.
In general:
- Findings of active rejection that are identified and treated promptly often respond well to treatment.
- Findings of interstitial fibrosis and tubular atrophy represent permanent scarring that cannot be reversed, but slowing its progression is an important goal of ongoing care.
- Mild changes detected on a surveillance biopsy may allow your team to intervene early, before significant damage occurs.
The best source of information about what your specific biopsy results mean for your transplant is your transplant nephrologist, who knows your full medical history.
Questions to ask your transplant team
- What is the main finding in my biopsy report?
- Is this rejection, and if so, what type and how severe?
- Will my immunosuppressive medications need to be changed?
- How quickly should I expect my kidney function to improve after treatment?
- Do I need a repeat biopsy, and if so, when?
- Is there any evidence of scarring in my kidney, and if so, how much?
- Are there any signs of infection, such as BK virus, in my biopsy?
- Is there any sign that the disease that damaged my original kidneys has come back?
- What are my donor-specific antibody levels, and how do they relate to my biopsy results?
- What can I do to help protect my transplanted kidney going forward?
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