Antibody-Mediated Rejection of the Kidney: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC
July 20, 2026

Antibody-mediated rejection, sometimes called humoral rejection or abbreviated AMR, is a condition in which the immune system of a person who has received a kidney transplant attacks the transplanted kidney using antibodies. Antibodies are proteins the immune system makes to target things it sees as foreign. In antibody-mediated rejection, these antibodies target the transplanted kidney and injure it primarily by attacking the lining of its small blood vessels. It is a leading cause of long-term transplant failure, and it is different from the other main form of rejection, in which immune cells rather than antibodies do the damage.

This article will help you understand the findings in your pathology report for antibody-mediated rejection, what each term means, and why it matters for your care. Because the diagnosis is based on a specific set of findings that appear together in the report, the sections below follow the three pieces of evidence that a pathologist and transplant team combine to make it: injury to the small blood vessels, a marker called C4d, and antibodies against the donor, measured in the blood.

What causes antibody-mediated rejection?

Every cell carries surface proteins called HLA antigens, which act like an identity badge the immune system uses to tell the body’s own tissue from foreign tissue. A transplanted kidney comes from another person and carries different HLA antigens. When the immune system produces antibodies against specific donor antigens, they are called donor-specific antibodies, usually abbreviated as DSA. These antibodies are the root cause of antibody-mediated rejection.

DSA can arise in two ways. Some people already carry them before the transplant, having been exposed to foreign HLA antigens through a previous transplant, a blood transfusion, or a pregnancy; this is why patients are tested for these antibodies before transplantation and matched carefully. Others develop them after the transplant, called de novo (newly formed) DSA, often months or years later, and this is especially likely when the medications that suppress the immune system are reduced, missed, or not fully effective. Once DSA are present, they travel to the transplanted kidney and bind to the HLA antigens on the lining of its small blood vessels. This binding triggers inflammation and a cascade of immune activity that injures the vessel lining, which is where the damage of antibody-mediated rejection is concentrated.

What are the symptoms of antibody-mediated rejection?

Antibody-mediated rejection often causes no symptoms, particularly in its early or chronic forms, and is detected only through blood tests or a biopsy. When it does cause symptoms, they reflect declining kidney function rather than anything specific, and may include:

A rise in the blood creatinine level, a waste product the kidney normally clears; this is often the first sign, found on routine bloodwork.
A drop in the amount of urine produced.
Protein in the urine.
A rise in blood pressure or fluid retention.

Because the early and chronic forms can be silent, this rejection is sometimes found only when a biopsy is done for another reason or as part of routine monitoring, or when donor-specific antibodies are detected on a blood test and a biopsy is done to see whether they are harming the kidney.

How is the diagnosis made?

Antibody-mediated rejection is diagnosed by combining findings from a biopsy of the transplanted kidney with a blood test for donor-specific antibodies. In a biopsy, a thin needle is used to take one or more small tissue cores, which a pathologist examines under the microscope using both ordinary light microscopy and special stains. Unlike most diagnoses, antibody-mediated rejection is not established by any single finding. Instead, the transplant team looks for three kinds of evidence, and your report is organized around them. The next three sections explain each one, because together they are what a report for this diagnosis actually contains.

Evidence 1: Injury to the small blood vessels (microvascular inflammation)

The hallmark of antibody-mediated rejection is inflammation of the kidney’s smallest blood vessels, called microvascular inflammation. Because the donor-specific antibodies attack the lining of these vessels, this is where the injury shows up, and pathologists measure it in two locations using scores that appear directly on the report:

Glomerulitis (the “g” score) — Inflammation within the glomeruli, the kidney’s tiny filtering units. Immune cells collect inside the small vessels of the glomerulus and clog them. The g score runs from 0 (none) to 3 (extensive).
Peritubular capillaritis (the “ptc” score) — Inflammation within the peritubular capillaries, the tiny vessels that run between the kidney’s tubules. Immune cells line up inside these vessels. The ptc score also runs from 0 to 3.

These two scores are often added together into a combined microvascular inflammation score (sometimes written as g + ptc). A higher combined score means more active injury and is one of the central pieces of evidence for the diagnosis. If your report lists a “g” score and a “ptc” score, this is what they describe.

Evidence 2: The C4d stain

C4d is a protein fragment left behind when antibodies activate part of the immune system called the complement system on the lining of the blood vessels. Because C4d sticks to the vessel wall at the site of the antibody attack, it acts as a footprint showing that antibodies have been at work. Pathologists detect it with a special stain, applied by immunohistochemistry or immunofluorescence, and look for it lining the peritubular capillaries.

A C4d-positive result is strong evidence of antibody activity and supports the diagnosis. Importantly, though, a C4d-negative result does not rule out antibody-mediated rejection: it is now well recognized that the injury can occur without detectable C4d, which is why C4d is only one of the three kinds of evidence rather than a requirement. This is a meaningful change from the older understanding, when a positive C4d stain was considered necessary, and it is why the microvascular inflammation score and the antibody blood test carry so much weight alongside it.

Evidence 3: Donor-specific antibodies in the blood

The third piece of evidence comes not from the biopsy, but from a blood test for donor-specific antibodies (DSA), the antibodies against the donor’s HLA antigens described earlier. Detecting these antibodies in the blood confirms that the immune system has mounted a response specifically against the transplanted kidney and links the injury observed under the microscope to its cause. The transplant team usually reports whether DSA are present and, often, how strong they are.

Sometimes the biopsy shows microvascular inflammation, but no donor-specific antibodies are found in the blood. Current classification recognizes these situations with specific labels, such as “probable antibody-mediated rejection” or microvascular inflammation without detectable antibodies. These findings are still taken seriously because they can behave like antibody-mediated rejection and carry a similar risk to the kidney, and they may prompt more detailed antibody testing. If your report or your team uses one of these terms, it means the picture is suggestive but does not meet every criterion, not that nothing is wrong.

Acute versus chronic antibody-mediated rejection

Antibody-mediated rejection is described as active (acute) or chronic, and your report will indicate which, because they reflect different stages and carry different outlooks.

Active (acute) antibody-mediated rejection — A current, ongoing attack, marked by the active microvascular inflammation described above. Caught early, it can sometimes be controlled with treatment.
Chronic (chronic active) antibody-mediated rejection — A long-standing process that has caused permanent, structural damage to the kidney’s blood vessels and filters, often on top of continuing active inflammation. The key finding here is transplant glomerulopathy, in which the walls of the glomerular vessels thicken and become multilayered from repeated injury; this is measured by a score called “cg” on the report. Chronic antibody-mediated rejection is now one of the leading causes of late transplant loss, and because the damage is partly permanent, it is harder to reverse.

Other findings described in the report

Alongside the features above, the report may describe additional findings that complete the picture:

Arteritis — Inflammation of the larger arteries, which can occur in antibody-mediated rejection as well as in cell-mediated rejection.
Thrombotic microangiopathy — Tiny blood clots forming in the small vessels, a sign of severe vascular injury.
Acute tubular injury — Damage to the cells lining the tubules, reflecting that the kidney’s filtering work has been disrupted.
Interstitial fibrosis and tubular atrophy — Scarring of the supporting tissue and shrinkage of the tubules, reflecting older, long-standing damage and helping show how much healthy kidney remains.

Antibody-mediated versus T-cell mediated rejection

There are two main ways the immune system can reject a transplanted kidney, and distinguishing between them is essential because they are treated differently.

Antibody-mediated rejection — The subject of this article. Driven by antibodies (donor-specific antibodies) that attack the lining of the kidney’s blood vessels, injuring mainly the glomeruli and the small capillaries. It is marked by microvascular inflammation, often a positive C4d stain, and donor-specific antibodies in the blood.
T-cell mediated rejection — Driven not by antibodies but by immune cells called T cells, which enter the kidney and attack the tubules and the supporting tissue directly. It is usually C4d-negative and is not associated with donor-specific antibodies.

The two can occur at the same time, called mixed rejection, which is more serious and requires treating both. This is one reason a transplant biopsy report carefully addresses the C4d stain, the blood vessel findings, and the tubular findings together, rather than any one alone. In general, antibody-mediated rejection is harder to treat and carries a poorer long-term outlook than T-cell mediated rejection.

What is the outlook?

The outlook for antibody-mediated rejection depends on whether it is active or chronic and on the extent of permanent damage. Active rejection caught early, before extensive scarring, has the best chance of responding to treatment and stabilizing kidney function. Chronic antibody-mediated rejection, with established transplant glomerulopathy, is more difficult, because a substantial part of the injury is permanent, and it is now recognized as one of the leading causes of transplant failure over the long term. Even so, treatment aims to slow the process and preserve function for as long as possible, and outcomes vary widely from person to person. The strongest signals of a more difficult course are a high degree of scarring on the biopsy, established transplant glomerulopathy, persistent donor-specific antibodies, and a declining kidney function despite treatment.

What happens after the diagnosis?

Antibody-mediated rejection is managed by the kidney transplant team, and the goal of treatment is to remove or reduce the donor-specific antibodies and calm the injury they cause. It is important to be honest that this is one of the harder problems in transplantation: there is currently no treatment specifically approved for antibody-mediated rejection, the available options rest on limited evidence, and they work better for active disease caught early than for established chronic disease. The biopsy findings and antibody results guide what the team considers. This is a general overview; the specific plan is individual, and this article does not recommend any particular treatment.

Removing antibodies — A procedure called plasma exchange (plasmapheresis) filters antibodies out of the blood and is often combined with intravenous immunoglobulin (IVIG), a preparation that helps neutralize and regulate the immune response.
Reducing antibody production — Medications that target the immune cells producing the antibodies, most commonly rituximab, are frequently added, though their benefit is not firmly established. Newer drugs that more deeply deplete antibody-producing cells are being studied for difficult cases.
Corticosteroids and adjusting immunosuppression — High-dose steroids are commonly used, and the transplant team reviews the ongoing immunosuppressant medications, since inadequate immunosuppression often underlies the development of donor-specific antibodies.
Monitoring — Donor-specific antibody levels and kidney function are monitored over time, and repeat biopsies are sometimes performed to assess whether the treatment has reduced inflammation. Because antibody-mediated rejection can persist or recur, monitoring often continues long term.

Prevention matters as much as treatment: careful matching before transplantation, monitoring for donor-specific antibodies, and maintaining adequate immunosuppression all reduce the risk, which is why the transplant team places so much emphasis on taking medications consistently and attending follow-up.

Questions to ask your doctor

Was my rejection active (acute) or chronic, and what does that mean for my kidney?
Were donor-specific antibodies found in my blood, and how strong were they?
Was the C4d stain positive or negative, and how does that affect my diagnosis?
What were my microvascular inflammation scores (g and ptc)?
Did my biopsy show transplant glomerulopathy or a lot of scarring?
Was there any T-cell mediated rejection present as well?
What treatment do you recommend, and how likely is it to help at this stage?
How will we know whether the treatment is working?
Will I need repeat biopsies or ongoing antibody testing?
What can I do to lower the risk of further rejection, and how important is taking my medications exactly as prescribed?
What is the long-term outlook for my transplant?
What symptoms should prompt me to contact the transplant team?