Kidney Transplant Rejection

Kidney transplant rejection happens when your body’s immune system recognizes your new kidney as foreign and tries to attack it. While this can sound frightening, understanding the signs and knowing that most rejection episodes can be successfully treated can help you protect your new kidney.

Table of contents

• What is kidney transplant rejection?
• Types of kidney transplant rejection
• How common is kidney transplant rejection?
• Signs and symptoms of kidney rejection
• How kidney rejection is diagnosed
• Treatment and prevention

What is kidney transplant rejection?

Kidney transplant rejection is your immune system’s way of protecting your body from your new kidney, which it perceives as a threat because it’s not your own^[1]. Even when your kidney donor is a good match, your body essentially recognizes the kidney as being “new” and reacts by trying to destroy it^[1].

When you receive a kidney from another person, the donor kidney acts as an alloantigen (a substance your body sees as foreign). In general, when transplanting tissue or cells from a genetically different donor, the alloantigen of the donor induces an immune response in the recipient against the graft^[3]. This response can destroy the graft if not controlled. The whole process is called allograft rejection^[3].

Allograft rejection is inflammation with specific changes in the transplanted kidney due to your immune system recognizing the non-self antigen in the transplanted organ, with or without loss of kidney function^[3]. Both innate and adaptive immune systems play a significant role in rejection, but the T lymphocytes (a specific type of white blood cell) are the principal cells that recognize the transplanted kidney^[3].

Types of kidney transplant rejection

There are several types of kidney transplant rejection, classified based on when they occur and what causes them.

Hyperacute rejection

Hyperacute rejection happens minutes after transplant, and it is related to preformed antibodies or blood type incompatibility^[3]. This type of rejection is rarely seen now due to the very sensitive tests performed before the transplant to ensure compatibility.

Acute rejection

Acute rejection happens within the first 12 months of a transplant^[1]. It’s more likely to occur within the first several weeks. Acute means it happens quickly. If you don’t have an acute rejection episode after 12 months, you may be less likely to have one as long as you take your medication as prescribed^[1].

Acute rejection can happen any time after transplant, usually within days to weeks after the transplant^[3]. It is divided into two main types:

• Antibody-mediated rejection (ABMR) usually demonstrates evidence of circulating donor-specific antibodies and immunological evidence of antibody-mediated injuries to the kidney, such as inflammation of glomeruli (called glomerulitis) or peritubular capillaries (called peritubular capillaritis)^[3].
• Acute T-cell-mediated rejection (TCMR) is characterized by lymphocytic infiltration of the tubules, interstitium, and sometimes the arterial intima^[3].

Chronic rejection

Chronic rejection typically happens slowly and over several years^[1]. Your body’s immune system slowly and constantly fights your new kidney, which leads to kidney damage. Chronic rejection happens to kidney recipients more often than acute rejection. It can happen years after a kidney transplant. The signs can often be subtle and unnoticeable because the rejection is gradual^[1].

Silent rejection

Silent rejection, also known as subclinical acute rejection, is a type of transplant rejection that progresses slowly, often without obvious symptoms^[22]. Research shows that the rejection process begins well before symptoms develop. In silent rejection, you will likely feel normal^[22].

How common is kidney transplant rejection?

Some degree of rejection is very common. About 15% to 20% of people who receive a new kidney will experience some type of rejection^[1]. The severity of the rejection varies. Even when someone is well matched with their transplant kidney in terms of blood group and tissue type, some degree of rejection is common^[9].

Although kidney rejection is most common in the first six months after transplant surgery, it can occur years later^[1]. While your risk of transplant rejection goes down over time, it never goes away completely^[1]. Rejection can occur at any time after your transplant, but it’s more likely to happen within the first 6 months^[5].

Despite immunosuppression medications, 10 to 20% of patients will experience at least one episode of rejection^[8]. However, it’s important to remember that most rejections are mild and easily treated by making adjustments to immunosuppression medication dosages^[8].

Signs and symptoms of kidney rejection

If you receive a kidney transplant, you should be aware of the signs of organ rejection and let your healthcare provider know if you experience any of them^[1]. Many of these signs are nonspecific and can be caused by problems that aren’t rejection.

Common signs of rejection may include^[1]:

• Fever higher than 101 degrees Fahrenheit (38 degrees Celsius)
• Flu-like symptoms like chills, body aches, headache or nausea
• New pain or tenderness around your kidney area (the transplant site)
• Sudden weight gain greater than 2 to 4 pounds within a 24-hour period
• Peeing less often
• Swelling in your body

Other symptoms reported include^[5]:

• Fever higher than 100 degrees F
• Flu-like symptoms such as chills, headaches, dizziness, muscle aches
• Nausea or vomiting
• Swelling or sudden increase in weight
• Decrease in the amount of urine you’re passing

If you think you’re experiencing any of these symptoms, contact your transplant team immediately^[1]. Most rejection episodes do not have symptoms and are usually picked up through routine bloodwork^[8]. However, if symptoms do occur, they indicate that damage has already been done to your kidney by the time your body shows these signs^[22].

How kidney rejection is diagnosed

Your transplant team will perform periodic blood tests to make sure your body is accepting your new kidney^[5]. There are other signs of rejection that can only be detected by routine blood testing. This is why blood is frequently drawn during your hospitalization and at your follow-up clinic visits^[8].

If your creatinine level (a measure of kidney function) starts rising, this may indicate kidney rejection^[5]. Research shows that serum creatinine is a late indicator of kidney injury, meaning that damage has already been done by the time this test shows a positive result^[22].

During your follow-up appointments, your transplant team will conduct a series of tests to help detect any signs of rejection. These tests include^[5]:

• Bloodwork: Your blood will be drawn at every visit to monitor for signs of low white blood cell count, low red blood cell count and low platelet count, which can indicate infection, anemia, or lack of an ability to form blood clots.
• Renal ultrasound: This is a non-invasive test performed in a radiology lab. It uses sound waves to look at your kidneys, your bladder and your blood vessels for signs of damage.

A kidney biopsy (a procedure where a small tissue sample is taken from the kidney) is almost always necessary to determine if rejection is actually occurring^[8]. A biopsy can ultimately diagnose silent rejection, but biopsies are painful and invasive^[22].

Treatment and prevention

Preventing rejection

Medications called immunosuppressants help to prevent and treat a kidney transplant rejection by blocking your immune system from damaging your kidney^[1]. People who receive a kidney transplant take immunosuppressants. These medications must be given for the rest of your life to fight rejection^[6].

Taking your transplant medicines is one of the most important parts of keeping your new organ healthy^[21]. Even missing one dose of medicine can cause your body to reject your new kidney^[21]. It’s very important for you to take your medications exactly as prescribed, obtain laboratory tests and attend all follow-up appointments with your provider after a kidney transplant^[1].

To reduce your risk of kidney rejection^[5]:

• Take your medicines as directed
• Lead a healthy lifestyle
• Keep your follow-up appointments
• Immediately let your transplant team know if you have any problems or complications

Additional steps you can take to reduce your risk include^[5]:

• Eat a healthy diet, low in salt and fat
• If you have diabetes, watch your blood sugar
• Incorporate exercise into your daily routine as directed by your doctor
• Manage stress and watch for signs of depression or anxiety
• Wash your hands regularly
• Stay away from people who are sick and avoid germs
• Drink lots of water to stay hydrated
• Contact your transplant team with any issues

Treating rejection

Your healthcare provider can usually recognize and treat a kidney rejection before it causes any major or irreversible damage^[1]. If rejection occurs, your healthcare provider prescribes a higher dose or a different combination of immunosuppressant drugs^[1].

Kidney rejection is a common complication after kidney transplant, and it does not mean your kidney will be removed or that you will have kidney failure^[5]. If you do experience kidney rejection, doctors can usually treat the condition by adjusting your immunosuppressive medicines^[5].

If and when you suffer an episode of rejection, remember it does not mean you will lose your new kidney or that your new kidney is failing^[8]. Most rejections are mild and easily treated by making adjustments to immunosuppression medication dosages^[8].

Rejection episodes are most often managed by making adjustments to your medication dosages^[8]. Treatment of rejection usually requires a few days of hospitalization, allowing doctors to administer alternative immunosuppressants and observe your progress^[8].

Because anti-rejection medications affect the immune system, people who receive a transplant will be at higher risk for infections^[6]. A balance must be maintained between preventing rejection and making you very susceptible to infection^[6]. Blood tests to measure the amount of medication in the body are done periodically to make sure you do not get too much or too little of the medications^[6].