Kidney Transplant Rejection: What You Need to Know

Kidney Transplant Rejection: What You Need to Know

Kidney Transplant Rejection: What You Need to Know

Since the first kidney transplant more than 60 years ago,1 doctors have developed a deeper understanding of how to protect donated organs. With newer medications and improved management, it’s less likely transplanted kidneys will undergo rejection by the immune system.

That’s not to say doctors have completely eliminated the risk of kidney transplant rejection, though. Unfortunately, while many kidneys will last much longer, the median life of a kidney transplant is still only ten years. Understanding the risks and early warning signs of rejection gives you the best chance of a successful kidney transplant.

What Causes Kidney Transplant Rejection?

“All body cells carry a special signature of the person indicating that they are healthy and they are part of you, including the cells in the kidney,” says Nikhil Agrawal, MD, Medical Director of Kidney Transplant at CareDx. That unique code helps your immune system recognize which cells belong and which are foreign.

Most kidney transplants come from someone else, so those cells have the signature of the donor, and not the recipient. Your body will see these foreign cells and believe they are a threat, so the immune system tries to fight them off, just like it would in the case of infections or cancer. The immune system sends various cells (T-cells are one example) to do this job, along with helpful substances called antibodies.

Unfortunately, the immune system may see the cells of a transplanted kidney as invaders, rather than part of something your body needs. This response can lead to kidney rejection. “Immunosuppression medications after kidney transplant can dampen the immune response. But sometimes that is not enough, and the immune system still reacts against a kidney,” says Dr. Agrawal.

Determining the Type of Kidney Transplant Rejection

There are three main types of kidney transplant rejection. Each impacts the potential success of a transplant in different ways, with steps you can take with your medical team to reduce the risk. The types are based on when the rejection occurs:

  • Hyperacute transplant rejection: Hyperacute rejection happens within just a few minutes or hours of receiving a new kidney. In such cases, your immune system already has antibodies to fight the specific type of foreign cells involved. That readiness means it can mount a prompt response. While hyperacute rejection completely destroy the new kidney, it’s extremely rare in transplants today. Transplant teams have developed better ways to determine beforehand if a potential organ will clash with existing antibodies.
  • Acute transplant rejection: An acute transplant rejection occurs three months to one year after surgery.2 Doctors have better medications today to suppress, or reduce, the immune system’s response, to keep it from attacking a new kidney. Still, acute rejection occurs about 10% of the time.3 When it happens, doctors study your immune response to further categorize the rejection. Doing so helps them create an effective treatment plan. The three main subgroups are based on the part of the immune system that has responded:
    • Antibody-mediated rejection (ABMR)
    • T-cell mediated rejection (TCMR)
    • Mixed (combination of ABMR and TCMR)
  • Chronic transplant rejection: Chronic kidney transplant rejection starts a year or more after the transplant surgery. This is the most common type of transplant rejection. Scarring forms slowly and eventually damages your transplanted kidney. The rejection usually occurs because immunosuppression medications are not working as well as expected. It can also occur when people with transplanted kidneys don’t take their medications like they should.4

Lowering Kidney Transplant Rejection Rates

Several advances in kidney transplant medicine have increased success for people needing a new organ. For example, doctors use multiple factors to determine if a donated kidney is a good match for a particular recipient. When you need a kidney transplant, doctors look at:

  • Blood type matching, which ensures the kidney comes from a person with the same blood type as yours
  • Tissue type matching, which compares several genetic markers in your body to those of your donor, to coordinate as closely as possible
  • Crossmatching, which tests whether antibodies in your blood will react negatively with the donor’s blood

Doctors also have a better understanding of how to prescribe immune-suppressing medications. There are multiple medications, and the correct combination depends on many factors. Your doctor will develop a plan unique to your transplant situation, for the best outcome.

Together, these efforts before and after surgery have increased the success of kidney transplants for many people. According to a 2021 review in the New England Journal of Medicine:5

  • Acute rejection has fallen from 50% in the 1970s to around 10% today.
  • The long-term survival rates for kidney transplants from deceased donors increased from 66% in 1999 to 78% in 2015.
  • For living-donor recipients, the survival rate similarly increased, from 80% to 88% over the same period.

Transplant Rejection Risk Factors

If you receive a kidney transplant, your greatest risk for rejection comes from non-compliance with medications. Not taking your medications as prescribed, or missing doses, can put you at higher risk for rejection. Without immunosuppression medications, your immune system may target your new kidney.

Other things that might increase your risk of rejection include6:

  • Receiving a kidney from a deceased donor rather than a living one
  • More mismatches of human leukocyte antigens (HLAs) in the cross-matching process— HLAs tell your immune system whether cells are part of your body or foreign
  • Multiple transplants for a single person
  • Race and sex (rejection is more common in Black people and women)

Kidney Transplant Rejection Symptoms

The symptoms of kidney rejection vary, depending on the type of rejection involved:

Hyperacute rejection symptoms

Hyperacute rejections occur soon after an organ is transplanted, with symptoms that can include:

  • High fever
  • Oliguria (low urine output)

If you have a hyperacute rejection after transplant, doctors will immediately remove the kidney.

Acute rejection symptoms

Symptoms of acute kidney transplant rejection can include7:

  • Fever
  • Increase in the blood of a waste product called creatinine, which kidneys remove when functioning
  • Low urine levels
  • Pain and tenderness in the area of the new kidney
  • Rapid, unexplained weight gain
  • Sudden spike in blood pressure
  • Swelling in your hands and feet

The only way to diagnose an acute transplant rejection is with a renal biopsy. Doctors take a small sample of tissue from your new kidney through a needle while you are under anesthesia. They send it to a lab where a pathologist looks for signs of rejection.

Chronic kidney rejection symptoms

Most people don’t experience symptoms from chronic kidney rejection early on. Over time, though, you may notice signs of kidney failure as your kidney sustains more damage. These symptoms can include:

  • Metallic taste in your mouth
  • Nausea and vomiting
  • Very low urine levels

Preventing Transplant Rejection

The best way to reduce the risk of transplant rejection is with immunosuppression. Your doctor will prescribe one or more medications to keep your immune system from attacking your new organ.

Most people need to take these medications exactly as prescribed for the rest of their lives. Missing doses of the medications or not taking them the right way can lead to kidney damage and eventually to kidney transplant rejection.

Regular checkups and monitoring from your doctor are also important to identify any potential signs of rejection. “Many rejections are actually not severe, and a person doesn’t have symptoms they would notice. They may only know from monitoring tests that indicate a problem,” says Dr. Agrawal. “That’s why getting routine blood and urine lab tests is so critical.”

Treatment to Reverse Kidney Transplant Rejection

Options to save a transplanted kidney depend on the type of rejection involved. Unfortunately, there is no treatment for hyperacute transplant rejection. Doctors will remove the rejected kidney and you will restart dialysis.

Treatment for acute kidney rejection depends on the subtype involved — ABMR, TCMR or mixed. Most people with an acute rejection get intravenous (IV) immunosuppressive medications for several days to suppress their immune system. Early diagnosis and prompt treatment can prevent further kidney damage and help the new organ recover. In many cases, doctors can intervene before too much damage occurs, successfully reversing acute kidney transplant rejection.8 If treatment works, you will continue taking immunosuppression medications.

Chronic kidney transplant rejections pose a greater challenge. If signs of rejection become noticeable early on, your doctor may be able to adjust your medications to limit further damage. Unfortunately, many people don’t experience symptoms until later, when the transplanted kidney may have become too damaged to save. That risk demonstrates the importance of taking immunosuppressants exactly as prescribed, as well as identifying chronic rejection as early as possible

 Find more resources for people receiving kidney transplants.

This information is not intended or implied to be a substitute for professional medical advice from your healthcare provider. You should always seek the advice of your physician or medical team with any questions you may have regarding your specific medical condition.


1. National Kidney Foundation
2. National Library of Medicine, Acute Transplant Rejection
3. Journal of the American Society of Nephrology
4. MedlinePlus
5. New England Journal of Medicine
6. Canadian Journal of Kidney Health and Disease
7. Stony Brook University Hospital
8. Clinical Journal for the American Society of Nephrology