Transplant Rejection

Transplant rejection occurs when the body’s immune system attacks a newly transplanted organ or tissue, recognizing it as foreign. While this complication can be serious, early detection and proper treatment with medications can often reverse rejection and protect the transplanted organ.

Table of contents

• What is transplant rejection?
• Why rejection happens
• Types of rejection
• Signs and symptoms
• How rejection is diagnosed
• Treatment approaches
• Preventing rejection

What is transplant rejection?

Transplant rejection is a process in which a transplant recipient’s immune system (the body’s natural defense system) attacks the transplanted organ or tissue^[1]. This happens because your body views the new organ as a foreign object rather than as part of your own body^[2].

Even when a donor organ is a good match, your body recognizes the organ as “new” and may react by trying to destroy it. The immune system reacting to an organ that has been transplanted into your body is called rejection^[2]. This process can affect transplants of kidneys, liver, heart, lungs, and pancreas^[4].

Although rejection is most common in the first six months after transplant surgery, it can occur years later^[2]. While your risk of transplant rejection goes down over time, it never goes away completely. The good news is that having an episode of organ rejection does not necessarily mean you will lose your new organ^[16].

Why rejection happens

Your body’s immune system normally protects you from substances that may be harmful, such as germs, poisons, and sometimes cancer cells^[1]. These harmful substances have proteins called antigens on their surfaces. When antigens enter the body, the immune system recognizes that they are foreign and attacks them.

When a person receives an organ from someone else during transplant surgery, that person’s immune system may recognize that it is foreign. This happens because the immune system detects that the antigens on the cells of the organ are different or not “matched”^[1]. Organs that are not matched closely enough can trigger transplant rejection.

To help prevent this reaction, healthcare providers type or match both the organ donor and the person receiving the organ. The more similar the antigens are between the donor and recipient, the less likely that the organ will be rejected^[1]. Tissue typing ensures that the organ or tissue is as similar as possible to the tissues of the recipient. However, the match is usually not perfect. No two people, except identical twins, have identical tissue antigens^[1].

Healthcare providers use medicines to suppress the recipient’s immune system. The goal is to prevent the immune system from attacking the newly transplanted organ. If these medicines are not used, the body will almost always launch an immune response and destroy the foreign tissue^[1].

Types of rejection

There are three main types of rejection that can occur after an organ transplant. Each type differs in when it occurs and how quickly it develops^[1][6].

Hyperacute rejection

Hyperacute rejection occurs within minutes to hours after the transplant when the antigens are completely unmatched^[1]. This type is extremely rare today because it can almost always be prevented by tissue cross-matching^[6]. It is caused by pre-formed antibodies directed against the donor organ cells and completely destroys the kidney transplant^[6].

This type of rejection is seen when a recipient is given an organ that is a different blood type. For example, when a person with type B blood receives an organ with type A blood^[1]. If hyperacute rejection occurs, the transplanted organ must be removed right away so the recipient does not die^[1].

Acute rejection

Acute rejection may occur any time from the first week after the transplant to three months afterward^[1]. It occurs days to weeks after transplantation when the immune system recognizes the grafted organ as foreign and mounts an immune response^[4]. Acute rejection happens within the first 12 months of a transplant and is more likely to occur within the first several weeks^[2].

About 15 percent or less of patients who receive a deceased donor kidney transplant will have an episode of acute rejection^[6][7]. All recipients have some amount of acute rejection^[1]. When treated early, it is reversible in most cases^[6]. Healthcare providers will adjust medications if they diagnose acute rejection in hopes of preventing the body from damaging the organ^[2].

Acute rejection can involve different mechanisms. Cellular rejection means that specific white blood cells called T lymphocytes cause the rejection. The immune system can also reject the new organ through antibodies, which is called antibody-mediated rejection^[2][7].

Chronic rejection

Chronic rejection can take place over many years. The body’s constant immune response against the new organ slowly damages the transplanted tissues or organ^[1]. This type typically happens slowly and over several years, with the body’s immune system slowly and constantly fighting the new organ, which leads to organ damage^[2].

Chronic rejection happens to organ recipients more often than acute rejection and can happen years after a transplant^[2]. The signs can often be subtle and unnoticeable because the rejection is gradual^[2]. It is thought that controlling blood pressure, blood sugar, and cholesterol levels can help prevent chronic rejection^[6].

Signs and symptoms

If you receive an organ transplant, you should be aware of the signs of organ rejection and let your healthcare provider know if you experience any of them^[2]. Many of these signs are nonspecific and can be caused by problems that aren’t rejection, but it’s important to contact your transplant team immediately if you notice them.

Common symptoms may include^[1][2]:

• Fever higher than 101 degrees Fahrenheit (38 degrees Celsius)
• Flu-like symptoms, including chills, body aches, headache, nausea, cough, and shortness of breath
• General discomfort, uneasiness, or ill feeling
• Pain or swelling in the area of the organ (rare)
• New pain or tenderness around the transplant site
• Sudden weight gain greater than 2 to 4 pounds within a 24-hour period

The symptoms depend on the transplanted organ or tissue. The organ’s function may start to decrease^[1]. For example, people who reject a kidney may make less urine or pee less often, and people who reject a heart may have symptoms of heart failure^[1][2].

Signs that the organ is not working properly depend on which organ was transplanted and may include^[1]:

• High blood sugar (pancreas transplant)
• Less urine released (kidney transplant)
• Shortness of breath and less ability to exercise (heart transplant or lung transplant)
• Yellow skin color and easy bleeding (liver transplant)
• Swelling in hands, feet, or legs
• An elevated temperature
• An increase in blood pressure

How rejection is diagnosed

Your healthcare provider can usually recognize and treat organ rejection before it causes any major or irreversible damage^[2]. During your follow-up appointments, your transplant team will conduct a series of tests to help detect any signs of rejection^[14].

Your provider will examine the area over and around the transplanted organ^[1]. The diagnosis of acute rejection is based on clinical features involving the grafted organ and is confirmed by diagnostic laboratory studies, including tissue biopsy^[4].

Diagnostic tests may include^[1][14]:

• Bloodwork: 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. Your blood may also be tested to look at kidney or liver function. If your creatinine level starts rising, this may indicate kidney rejection^[14].
• Biopsy: A biopsy of the transplanted organ can confirm that it is being rejected. This is the only way to definitively diagnose acute rejection^[1][6]. Under local anesthesia, a small fragment of your organ is removed with a needle and examined under a microscope. A pathologist (a doctor who specializes in examining tissues) will determine whether rejection is present. A routine biopsy is often performed periodically to detect rejection early, before symptoms develop^[1].
• Imaging tests: When organ rejection is suspected, one or more tests may be done to assess the transplanted organ, including abdominal CT scan, chest x-ray, heart echocardiography, kidney arteriography, kidney ultrasound, or renal ultrasound^[1][14].

Treatment approaches

The goal of treatment is to ensure that the transplanted organ or tissue works properly and to suppress your immune system response^[1]. Treatment primarily involves immunosuppressive medications (medicines that reduce immune system activity) to induce tolerance of donor cells and prevent rejection^[4].

If rejection occurs, your healthcare provider prescribes a higher dose or a different combination of immunosuppressant drugs^[2]. Several medications can be used to reverse acute rejection, including^[6]:

• Intravenous steroids (Prednisone)
• Antibodies
• Other immunosuppressants

Corticosteroids serve as the primary treatment for acute T-cell-mediated rejection, while severe or steroid-resistant cases may require T-cell-depleting agents, like Thymoglobulin^[7].

For antibody-mediated rejection, the most common treatment is plasmapheresis, although its effectiveness is still debated^[7]. Other current therapies, such as intravenous immunoglobulins, anti-CD20 antibodies, complement inhibitors, and proteasome inhibitors, are also used to varying degrees^[7].

Organ rejection often requires a biopsy and a hospital stay, along with tests and monitoring. Certain types of rejection may require more intense or lengthy treatments^[16]. Despite maximizing treatment of rejection episodes, some cases may not be reversed and may impact organ survival^[7].

Preventing rejection

While organ rejection may not be entirely preventable, there are important steps you can take to reduce your risk. You are the most important member of your transplant team^[16].

Take your medications exactly as prescribed

After an organ transplant, antirejection medicines are used to prevent the body from rejecting the new organ. These medicines work by lowering the body’s immune response, called immunosuppression^[12]. With these medicines, the immune system is weakened enough to not reject the organ but still gives enough immunity to prevent severe infections.

People who receive an organ transplant take immunosuppressants for the rest of their lives. It is very important to take your medications every day, exactly as prescribed^[1][2]. Medications called immunosuppressants help to prevent and treat transplant rejection by blocking your immune system from damaging your organ^[2].

Antirejection medicines work in three phases^[12]:

• Induction medicines are given in a vein before and after the transplant to help get the body ready to accept the transplanted organ
• Maintenance medicines are taken for as long as you have a transplanted organ. They are used long-term to continue suppression of the immune system. You often take a combination of medicines after an organ transplant, which are started shortly after surgery
• Rejection treatments are medicines that are used if the body starts to reject the transplanted organ

Attend all follow-up appointments

It is very important to obtain laboratory tests and attend all follow-up appointments with your provider after a transplant^[2]. Regular blood tests are needed to check the amounts of medicine in the blood. Higher amounts of medicine in the blood can make side effects worse. If there isn’t enough medicine, your transplanted organ may not have enough protection^[12].

Lead a healthy lifestyle

In addition to taking your immunosuppressive medicines as directed, there are steps you can take to reduce your risk of rejection^[14]:

• 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

Communicate with your transplant team

Contact your transplant team with any issues^[14]. If you get sick, or another doctor prescribes you a medication, you will need to let your transplant team know. They will have to determine the nature of your illness and whether it relates to your transplant, if a prescribed medication is best for you, and if the medication will interact with your immunosuppressants^[16].

Report any symptoms of rejection to a healthcare professional right away^[12]. Early diagnosis and intervention of transplantation rejection are critical to prevent the loss of donor organs and tissues^[4].

While an infection does not automatically result in organ rejection, infections do increase the risk of rejection, especially if they require medications that compromise your immunosuppressants^[16]. Good hand washing, vaccinations for you and your family, food safety practices, and specific guidelines pertaining to your transplant can help you stay healthy^[16].