What is Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)?
Kidney transplantation is currently the best treatment for people with severe kidney disease. This treatment improves a patient’s quality of life and lifespan, compared to treatments like dialysis. One of the main threats to this treatment’s success is the body rejecting the new kidney. Other factors that can lead to failure of the donate kidney include recurring disease, formation of fibrous tissue, toxicity from certain drugs used to prevent rejection, and damage caused by the BK virus.
Rejection of the new kidney can occur at various stages – immediately after the surgery, a few days later, within weeks or even after a year. Chronic kidney transplant rejection is when the donate kidney fails after a year from the transplant, without obvious signs of acute rejection, drug toxicity or kidney disease. It’s now more common to use biopsy-specific results to explain continual damage after a transplant. This helps to identify whether chronic immune damage is to blame or if it’s interstitial fibrosis and tubular atrophy, which are unspecified changes.
What Causes Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)?
CKTR, or chronic kidney transplant rejection, can happen because of the body’s immune response, often in patients who haven’t taken enough immunosuppressant medicine or aren’t following their prescribed medication regime accurately. One study showed that acute rejection led to a later loss of the kidney transplant in about 15% of patients. Patients who had experienced acute rejection had more inflammation and damage of the kidney tissue, which led to the early failure of the transplant.
Another study found that not adhering to immunosuppressant medication five years after their transplant was linked to an increase in inflammation and kidney tissue damage.
There are also non-immune related factors that can lead to the failure of the transplanted kidney. These can include issues with the kidney starting to function after the surgery, side effects from the immunosuppressant medication, the original kidney disease coming back, as well as conditions like diabetes, high blood pressure, and high lipid levels. These factors can speed up the natural aging process of the transplanted kidney, and cause further damage which can contribute to its failure.
Risk Factors and Frequency for Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)
Alloimmunity, a reaction of the immune system to foreign bodies, is one of the main reasons for the failure of transplanted organs. This has been reported in several studies. For example, a study by Nankivell and colleagues noted that nearly 26% of transplants showed silent rejection within the first year. Another research group known as the DeKAF studied 173 patients who underwent a kidney transplant. They discovered that patients who tested positive for certain markers known as DSA or C4d deposition or both had a higher risk of transplant failure two years after the operation.
Another study conducted by Sellares and team investigated why transplants failed in 60 out of 315 patients. They found that the occurrence of rejection mediated by antibodies increased over time, especially after the five-year mark post-transplant. Furthermore, biopsies done by Stegall and company found moderate to severe scarring in 13% to 17% of patients, one and five years post-transplant, respectively. Alarming to note is that 23% of the transplants who had a biopsy showed a progression in scarring from mild to severe forms.
- Nankivell’s study showed a 26% incidence of silent rejection in the first year after a transplant.
- The DeKAF group discovered greater risks of transplant failure in patients who tested positive for DSA or C4d deposition markers or both.
- Sellares’s research found an increased occurrence of antibody-mediated rejection, particularly after five years post-transplant.
- Stegall’s research identified progressive scarring in 13% to 17% of patients one to five years post-transplant, with 23% showing progression from mild to severe forms.
- However, only 5% of patients treated with a medication called tacrolimus showed signs of a specific type of lesion linked with chronic antibody-mediated rejection, hinting that tacrolimus might help prevent this complication.
Signs and Symptoms of Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)
Chronic kidney transplant rejection (CKTR) is a serious condition that needs to be diagnosed accurately. This starts with a detailed medical and personal history, as well as a comprehensive physical check-up. During this time, healthcare professionals should ask whether the patient has been taking their medication regularly, if they’ve had a kidney transplant before, whether they’ve experienced previous transplant rejection, and if they have known sensitivities to specific human leukocyte antigens (HLAs).
Some signs pointing towards CKTR could be an unexpected drop in levels of immunosuppressive drugs, which might indicate that the patient isn’t taking their medication as advised. This could be because of issues such as not being able to afford health insurance, so it’s crucial to ask about this. A review of all medications the patient is taking is important too, as some can interfere with immunosuppressant drugs, causing either rejection or toxicity.
- Regular medication intake
- Previous kidney transplant
- History of transplant rejection
- Sensitivity to specific HLAs
- Health insurance coverage
- All currently prescribed medications
The physical signs of CKTR are often vague and can include high blood pressure, swelling in the legs, and feeling unusually tired. It’s worth noting that you typically won’t see fever or tenderness around the transplanted kidney in cases of CKTR. As the condition progresses, symptoms of kidney failure and high levels of urea in the blood (uremia), which include changes in urine output, nausea, vomiting, experiencing a metallic taste in the mouth, heart-related complications, and ‘asterixis’ (a type of tremor), could become evident.
Testing for Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)
Just like with any other health problem, early detection of Chronic Kidney Transplant Rejection (CKTR) is key to successful treatment. This usually starts with frequent check-ups: every two weeks for the first three to six months post-transplant, monthly visits from month seven to twelve, and finally, every two to three months after the first year.
Several laboratory tests may be carried out to keep an eye on how well the transplanted kidney is functioning. In particular, doctors would look at results from blood tests that measure serum creatinine (Cr) and estimated Glomerular Filtration Rate (eGFR) levels. The eGFR test is thought to be a more accurate way to assess how well the kidney is performing. Other methods to assess the kidney’s function include Iothalamate GFR and cystatin C tests – these can be especially useful when other tests may not give an accurate picture due to factors such as high or low muscle mass. The presence of protein in the urine (more than 500 mg/day) may also be a sign that the kidney is not functioning well.
Donor-Specific Antibody (DSA) tests can show how a patient’s body is reacting to the transplanted kidney. These tests are usually carried out in a lab that specializes in human leukocyte antigen (HLA) investigations. A decrease or disappearance of DSA can indicate a positive response to the treatment. However, not all cases of tissue damage show a correlation with DSA levels. Constant monitoring for DSA can be a way to detect potential problems before they cause permanent damage.
Doctors may also use Doppler ultrasound (US) as a non-invasive method to check on the transplanted kidney. US can reveal issues with the blood flow in the kidney, which can be a sign of problems with its function. A special technique called Contrast-Enhanced Ultrasound (CES) can also be used to monitor the blood flow and kidney function in greater detail. This method uses tiny gas bubbles to assess the blood flow in the kidney following an injection of a contrast medium.
Doctors may also request a biopsy to assess the health of the kidney, which involves taking a small sample of kidney tissue for examination. This can provide visual evidence of the condition of the kidney and potential factors contributing to its dysfunction. In this process, the presence of a protein called C4d in blood vessels around the kidney can indicate damage caused by the immune system’s antibodies attacking the kidney.
The Banff classification, a diagnostic criteria system for kidney transplant rejection, provides a structure to interpret the findings from the biopsy and other tests. This classification details symptoms and signs associated with different types of kidney transplant rejection – Chronic Active Antibody-Mediated Rejection (CAAMR) and Chronic Active T-cell-Mediated Rejection (CATMR).
Treatment Options for Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)
Chronic kidney allograft rejection (CKTR) can’t be reversed once diagnosed, so preventing and treating acute rejection (AR) early on is crucial. The right balance of immunosuppressive drugs and patient compliance can reduce the chance of AR, which in turn lowers the risk of CKTR. Optimizing Human leukocyte antigen (HLA) matching, which checks how well the donor’s organ matches the recipient’s, can help dodge early graft injury, and thus reduce the risk of loss of the graft.
In the United States, most immunosuppressant regimens include calcineurin inhibitors (CNI), a class of drugs that helps prevent rejection. While CNIs are effective, they pose a risk of long term kidney toxicity. There have been suggestions to balance their benefits and potential harm by monitoring the drug levels in patients’ blood and sparing the usage of CNI where possible.
Reducing the target blood trough levels of CNIs (known as minimization) improves overall allograft function and carries a relatively low risk of AR. Using low dose CNI with mycophenolic acid (MPA) also reduces the risk of AR. That being said, combining full dose CNI and an mTOR inhibitor, a class of drugs that halt cell growth and reproduction, might increase the risk of kidney toxicity.
Shifting from CNI to another maintenance drug (known as conversion) may result in improved kidney function. Although, early conversion within one year might carry the risk of producing innate antibodies that increase the risk of antibody-mediated rejection, which effectively elevates the risk of CKTR.
Decreasing CNIs until they are completely stopped (known as withdrawal) brings with it an increased risk of rejection. This is especially true if withdrawal is implemented early, within six months post-transplant. Likewise, planning to sidestep CNIs from the onset (known as avoidance) also carries an increased risk of rejection.
Belatacept, an innovative protein that keeps T cells from activating, showed promise when compared to CNI based regimens. The protein led to a reduction in the risk of death or graft loss and improved kidney function.
Apart from medicine, blood pressure regulation and controlling lipid levels is vital. Not to mention, control of high cholesterol with certain medications also improves patients’ survival chances. Medications in the class of Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) might provide benefits to patients with chronic graft dysfunction and protein leakage in urine, although their use needs to be done carefully due to potential complications. Additional benefits are also expected from Vitamin D, but further studies are needed to confirm their effectiveness.
What else can Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney) be?
CKTR, or chronic kidney transplant rejection, can sometimes be misinterpreted because of its similarity to other conditions that cause issues with a transplanted kidney. Some conditions that need to be ruled out when diagnosing CKTR are:
- Calcineurin Inhibitor (CNI) Toxicity: CNI, a class of drugs that helps prevent organ rejection, could cause kidney issues, including increased blood pressure, blood vessel diseases, and kidney function problems, which contributes to fibrosis or tissue scarring. They can also cause health issues such as diabetes, high blood pressure, and high cholesterol, further damaging the kidney. Chronic CNI toxicity has similarities with CKTR as it results in IFTA, a type of scarring in the kidney tissue. Therefore, it’s crucial to differentiate between the two.
- BK-Virus Associated Nephropathy (BKVAN): This condition occurs when the BK virus grows due to weakened immunity after a kidney transplant. High levels of this virus can result in BKVAN, which causes similar scarring to CKTR. Tests are necessary to confirm the presence of the virus in the blood and in the kidney tissue.
- Recurrent or De-Novo Glomerular Disease: Sometimes, the original condition that damaged the kidneys, known as Glomerulonephritis (GN), can return or new forms of GN can emerge, causing issues in transplanted kidneys. Around 8.4% of late kidney transplant failures are due to recurrent GN. Conditions like Dense Deposit Disease and Focal Segmental Glomerulonephritis are prone to recurrence and carry a poor prognosis. Medical history, lab tests, and tissue assessments can differentiate GN from CKTR.
When diagnosing CKTR, doctors need to carefully evaluate these conditions and conduct proper tests to reach an accurate conclusion. This process is crucial to ensure proper treatment and to prevent further complications.
What to expect with Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)
The outlook and long-term success of a kidney transplant can be affected by factors such as the amount of scar tissue and whether any organ rejection can be reversed at the time of diagnosis. According to a study by Denisov and colleagues, checking levels of hemoglobin, creatinine, and protein in urine a year after transplant can provide useful predictions about how well the kidney transplant might fare.
It’s interesting to note that there’s actually a patented prediction tool available online in Russian. This tool reportedly has a 92% success rate in predicting how well the kidney will function three years after the transplant. However, more research is needed to confirm just how accurate this tool really is.
Possible Complications When Diagnosed with Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)
The main problem that can occur with CKTR (which stands for Chronic Kidney Transplant Rejection) is losing the transplanted kidney. This can lead to kidney failure and, in extreme cases, death. This is especially true for patients who may not be able to have another kidney transplant. Patients may suffer from mental health problems such as anxiety and depression. They are also at a higher risk of dying and may experience a lower quality of life if they have to start dialysis again. Research shows that patients with kidney transplant failure have less than a 40% chance of surviving for at least 10 years.
The most common cause of death in these patients is heart disease, followed closely by infections. Infections mainly occur because the patients have previously been on medicines that suppress the immune system. The financial cost of transplant rejection and going back on dialysis is also a big burden for both patients and society.
Common Complications of CKTR:
- Kidney failure
- Possibility of death
- Mental health issues (Anxiety and Depression)
- Higher risk of mortality and lower quality of life with dialysis re-initiation
- Common causes of death: Cardiovascular disease and infection,
- Economic burden of rejection and dialysis re-initiation
Preventing Chronic Kidney Transplant Rejection (Ongoing Rejection of a Transplanted Kidney)
People who have received a kidney transplant need advice and learning about several things:
They must understand the necessity of taking their prescribed medications faithfully. This is crucial for keeping their donated kidney healthy and functional for as long as possible. They should also be aware about the need for continued check-ups with their kidney transplant specialist.
They should also become familiar with the factors that increase the likelihood and the reasons for a condition known as chronic kidney transplant rejection. Moreover, patients should be able to recognize the warning signs and symptoms of this condition.
It’s important for them to know the potential problems and outcomes of chronic kidney transplant rejection. Finally, they need to understand the different treatments that can be used if they face chronic kidney transplant rejection.