What is Acute Transplantation Rejection?
Transplanting organs is the only treatment option for most severe cases of kidney, liver, heart, lung, and pancreas failure. Transplant rejection, which generally happens days to weeks after the transplantation, occurs when the immune system sees the new organ as a foreign object and attacks it, leading to the destruction of the organ. What differentiates intense immediate rejection from the standard acute rejection is the existence of pre-existing antibodies that cause instant rejection.
Matching the human leukocyte antigen (HLA) is one of the two main ways to prevent organ rejection after the transplant. It’s as crucial as doing a serum crossmatch. Immune-system-suppressing medicines like azathioprine and corticosteroids can also help to reduce the likelihood of an acute rejection. The main method of treatment consists of these immunity lowering medicines to avoid immediate rejection by making the recipient’s body tolerate cells from the donor’s organ.
When it comes to transplant rejection, diagnosing and treating it early is important to prevent the loss of the donor organs and tissues. There are not enough human organs available to meet the high demand for transplants, which is a big challenge in the successful practice of transplantation. As a solution, alternative strategies are employed, such as xenotransplantation (which uses pig organs), and donations from living people.
What Causes Acute Transplantation Rejection?
Acute transplant rejection is essentially the body’s immune system attacking the transplanted organ or tissue, which can lead to damage and possibly organ failure. This process usually involves T-cells and antibodies, the body’s defence systems.
Kidney transplants require a particularly careful match of what we call “MHC class II antigens.” These are proteins on the surface of cells that the immune system uses to recognize ‘self’ from ‘non-self.’ MHC class I antigen matching is also essential, but MHC class II is more critical for the survival of the transplanted organ.
Blood group compatibility is also crucial in transplants, because blood types A and B can be found on the cells that line blood vessels. If the transplanted organ and individual receiving the transplant do not have matching markers, the immune system can identify these as foreign and attack them.
A specific type of immune cell, called CD4+ T cells, are activated in these cases. They respond to these perceived foreign markers, producing substances that encourage the immune system to attack strongly, leading to the destruction of the transplanted organ over days or weeks.
Risk Factors and Frequency for Acute Transplantation Rejection
Getting a transplant comes with a significant risk of acute rejection, especially within the first few weeks after the procedure. About 50% to 70% of people who go through a transplant experience this. However, in kidney transplants, the chances of acute rejection have reduced significantly, thanks to improved use of drugs that suppress the immune system, such as calcineurin inhibitors. This advancement has greatly improved long-term outcomes for patients. That said, delayed graft function, which can be caused by increased vulnerability of the transplant or prolonged preservation times, is still a significant risk factor for acute rejection.
Signs and Symptoms of Acute Transplantation Rejection
Acute rejection is a medical event that can occur after an organ or tissue transplant procedure. Diagnosing it typically involves looking at patient symptoms, lab test results, and tissue biopsies. Generally, it happens days or weeks after a successful transplantation procedure. Patients may experience discomfort at the transplant site and might develop a fever.
Additional symptoms can appear depending on the type of organ or tissue that was transplanted. For example:
- In a kidney transplant, patients might experience little to no urine output, an increase in their serum creatinine levels (a marker of kidney function), and metabolic abnormalities like high potassium levels in their blood.
- In a pancreas transplant, patients might produce inadequate insulin, making it hard to regulate blood sugar levels normally.
- In a lung transplant, patients might face challenges with oxygen levels and carbon dioxide handling, leading to situations like low oxygen (hypoxia) and high carbon dioxide (hypercapnia) levels in their blood.
Acute rejection can also increase the risk of infections and other serious complications, including a life-threatening condition known as graft-versus-host disease. Quick diagnosis and treatment can often prevent complete organ or tissue failure from a single acute rejection episode. However, recurrent episodes can lead to a longer-term issue called chronic rejection.
Testing for Acute Transplantation Rejection
In order to prevent the rejection of a transplanted organ, doctors need to ensure the recipient and the donor are a good match. There are several lab tests they conduct to determine this:
First, there’s blood group testing. Here, the doctors make sure that the blood types of both the donor and the recipient are compatible. People with type O blood are considered universal donors, meaning they can donate to any blood type.
Next, a test called serum crossmatch is run. Here, donor cells are mixed with the recipient’s serum. If the recipient has antibodies that attack these cells, the test is considered positive, and the transplant cannot happen. A virtual crossmatch can also be conducted. Unlike the traditional method, this test matches the recipient’s antibodies against the donor’s antigens. It’s sometimes preferred because it can be faster and more accurate.
Lastly, doctors conduct an HLA typing. This looks at whether certain genes in the recipient and donor are compatible. This is a critical test in assessing compatibility.
Post-transplant, if an organ rejection is suspected, doctors might use lab tests and imaging to check on the organ but these tests are not diagnostic of acute rejection. Usually, a tissue biopsy is needed to confirm a rejection.
Images are used to keep an eye on the donor organ after transplantation. Often, ultrasound is used to monitor kidney transplants because it can provide a clear image of blood flow. But for lung transplants, x-rays and CT scans can better show signs of rejection, like fluid buildup and nodules. These imaging tests can also help doctors determine if other problems are happening with the transplanted organ, such as infections.
Treatment Options for Acute Transplantation Rejection
Acute rejection, or the body rejecting a newly transplanted organ, can happen with any transplant. It typically starts about a week after the transplant happens and is most likely during the first three months. If doctors suspect or confirm that acute rejection is happening, treatment should begin within three days. This often involves giving an IV of a medicine called methylprednisolone and regularly checking levels of a waste product called creatinine in the blood to see how the kidneys are functioning.
If someone has another rejection episode after the surgery, the same treatment with corticosteroids is given. If this treatment works well, they stop taking a medication called cyclosporin-A after nine months. However, they need to keep taking a daily dose of drugs that suppress the immune system. Common ones include azathioprine or prednisolone.
If the patient isn’t showing any improvement despite treatment, the doctors might consider doing another transplant. If someone gets a severe viral illness called cytomegalovirus infection because they received a kidney from a donor who had the virus and they didn’t, the treatment is often a medication called ganciclovir along with immune proteins that target the virus. If someone’s acute rejection isn’t responding to medication or IV antibodies, they might receive treatment that uses light to inactive certain proteins in the blood that are part of the immune response.
New treatments show promise for helping treat acute rejection. These treatments involve monoclonal antibodies, which are made in a lab and can attach to specific cells or proteins in the body. Some of these new treatments include anti-CD3, anti-CD25, anti-CD52, anti-CD20, and anti-CD40 antibodies. They all target different parts of the immune system that play a role in organ rejection. There are also antibodies that target parts of the immune system that cause inflammation, like anti-IL-6 and anti-TNF-α, which can reduce damage to the transplanted organ. These new treatments have the potential to increase how long a transplant lasts and reduce some of the side effects of current treatments.
What else can Acute Transplantation Rejection be?
When assessing symptoms after an organ transplant procedure, it is important to consider other health issues that might give similar signs. For instance, after a lung transplant, conditions like reimplantation response and infections need to be ruled out. Similarly, after a kidney transplant, a condition called acute tubular necrosis might be considered.
Different tests can be used to spot these issues. For example, a simple way to detect whether the transplant rejection or a CMV infection is causing symptoms is to examine a urine sample. IgM antibodies specific to CMV can help confirm a CMV infection. Also, Adenovirus nephropathy, a condition that can mimic transplant rejection, can be excluded through a blood test technique known as a polymerase chain reaction.
What to expect with Acute Transplantation Rejection
The future health of a patient with acute rejection is uncertain. However, people with a small genetic difference, like identical twins, have a good long-term outlook. The health outlook for those with acute rejection who are not genetically related can get better with drugs that reduce the immune response. Self-transplants have the best outlook and don’t need any treatment to stop the immune response.
Possible Complications When Diagnosed with Acute Transplantation Rejection
Graft-versus-host disease is a complication that can occur after organ transplants between genetically different individuals. Symptoms like skin rash, fever, bloody diarrhea, an enlarged liver or spleen, and difficulty breathing can occur about a week to two weeks after the transplant. The skin rash can get worse, leading to the skin peeling off. During acute rejection, the risk of various infections also increases, which can sometimes result in death. These infections can be bacterial, viral, fungal, due to parasites, or a mixture of these.
Immunosuppression, which helps prevent graft rejection, is often linked with a specific viral infection called CMV. Another issue that can occur, particularly after kidney transplants, is the return of the original disease that caused the need for the transplant in the first place. This return is usually suspected when there’s a pattern of alternation between periods of worsening function and stable function of the transplanted organ.
Another late complication that can happen after a transplant, is the development of cancer in the transplant recipient. Specifically, the chances of getting lymphoma and skin cancer are higher in people who have had a transplant.
Preventing Acute Transplantation Rejection
Patients should faithfully follow the treatment plan for existing conditions like kidney disease, diabetes, and cystic fibrosis. It’s crucial for them to fully understand the importance of taking their prescribed medications that prevent their body from rejecting a transplanted organ, as this will help improve their daily life. There’s a serious issue of organ rejection in some countries, impacting up to 50% of teenagers due to them not sticking to their medication plan.
