Introduction:
A kidney transplant is a surgical procedure that places a healthy kidney from a living or deceased individual into a person whose kidneys are not functioning correctly. An allograft, also known as an allogeneic transplant or homograft, is the transfer of tissues among genetically nonidentical people of the same species with compatible blood types. Individuals who receive a kidney transplant sometimes experience allograft failure. Kidney allograft failure is often a severe issue suggesting the need for restarting dialysis with associated morbidity and mortality.
What Are the Causes of Kidney Allograft Failure?
1. Non-Alloimmune Injury Mechanisms:
Chronic Tubulointerstitial Damage: Interstitial fibrosis and tubular atrophy are essential factors in kidney allograft failure. Tubulointerstitial damage is a nonspecific pathological finding in biopsies of the kidney. Damage to the kidney cells or nephrons leads to increased blood pressure in the kidney blood vessels and hyperfiltration in the remaining functioning kidney cells. This further leads to apoptosis (cell death), inflammation, and fibrosis, increasing slowly throughout the kidneys, thus causing further degeneration of the kidney function.
Calcineurin Nephrotoxicity: Calcineurin nephrotoxicity has been associated with kidney allograft failure for a long time. It is very likely that using calcineurin inhibitors during kidney transplantation causes a decline in the function of the graft and, eventually graft failure. However, studies have shown conflicting results, with better kidney function in some studies but an increase in transplant rejection in others. Nevertheless, it should be kept in mind that the advantages calcineurin inhibitors offer are far more critical than their contribution to graft failure.
Glomerulonephritis: Glomerulonephritis is the inflammation of the tiny filters (glomeruli) in the kidney. Glomerulonephritis in the transplanted kidneys can cause graft failure. Around twenty to fifty percent of kidney transplant recipients often have glomerulonephritis. Relapse of the original kidney disease in the transplanted kidney causes graft failure, although the recurrence rate varies. The increased recurrence rate also depends on the initial kidney disease.
Viral Diseases: Viral infections, such as the human polyomavirus BK, cause polyomavirus-associated nephropathy (PVAN) in around ten percent of renal transplant recipients. PVAN has been associated with five to fifteen percent of graft failures. PVAN damages the kidney allograft by a direct tubular injury that can lead to the development of tubulointerstitial damage in more than sixty percent of the cases. PVAN can be treated by reducing immunosuppression.
Diabetes: Pretransplant diabetes and new-onset diabetes after kidney transplant are pretty prevalent. A recent study has shown the rapid development of mesangial matrix expansion in insulin-dependent pre-transplant diabetes patients within five years after transplantation. Diabetes nephropathy after a kidney transplant can contribute to late graft failure.
Cardiovascular Factors: Recipient-related cardiovascular risk factors play an essential role in kidney allograft failure. The risk factors associated with cardiovascular complications after a kidney transplant include:
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Male gender.
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Age.
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High blood pressure before transplant.
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More extended dialysis before transplant.
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Increased pulse pressure post-transplant.
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Corticosteroid intake.
Cardiovascular diseases in kidney transplant recipients involve dysfunction and stiffness of the blood vessels and the development of heart failure during the progression of chronic kidney disease. Kidney transplantation results only in a partial recovery of these mechanisms, resulting in high cardiovascular risk due to the ongoing chronic kidney disease-related risk factors or transplantation-specific risk factors. Kidney transplantation improves both the structure and function of the heart. Five years post-transplant, some patients with persistent left cardiac chamber hypertrophy show a higher risk of graft failure than those with left chamber hypertrophy. In the elderly population, a positive history of heart failure during transplantation can lead to graft failure.
Kidney Allograft Vasculature: The blood vessels of the transplanted kidney are prone to damage, thus contributing to further allograft loss.
Non-immune Events: Non-immune conditions causing graft failure include intervening medical and surgical illnesses that are not related to the graft directly. Door-related causes, such as cause of death, age, kidney size, and kidney quality, and transplant procedure-associated causes, such as poor management of the organ, ischemia-reperfusion injury, and surgical complications, can lead to loss of kidney cells and chronic injury. An injury repair performed in the early transplant-related kidney injury can also cause renal dysfunction and fibrosis.
Recent advances towards better preservation techniques and prevention of the delay in graft function. It is essential to consider these causes despite their relations with the result contributing to more than a single cause of graft failure.
2. Alloimmune Injury Mechanisms:
The two significant rejections causing graft failure are: acute T-cell-mediated rejection, and
chronic T-cell-mediated rejection. Acute T-cell-mediated rejection is present in around twenty-four percent of the biopsies in the first months of transplantation, but it decreases with time. Acute T-cell-mediated rejection is rare ten years post-transplant. Acute T-cell-mediated rejection has been prevented with potent immunosuppressive therapy and effective anti-rejection treatment with corticosteroid drugs. However, the importance of acute T-cell-mediated rejection should not be underrated.
The impact of inflammation in atrophic areas on graft outcome has been extensively studied. It is preceded by acute T-cell-mediated rejection. Chronic-cell-mediated rejection is related to graft failure, but its response to increasing immunosuppression has not been reviewed yet.
How To Manage Kidney Allograft Failure?
Allograft failure is associated with psychological and medical morbidity. Such patients are at a higher risk of hospitalization, low physical functioning, and depression. Patients with failed kidney allografts returning to dialysis are also at increased risk. The higher risk of mortality on dialysis is found across the age group from eighteen to seventy years, with or without diabetes. Management can be done through,
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Repeating the transplant.
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Management of immunosuppression.
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Allograft nephrectomy.
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Management of chronic kidney disease.
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Palliative care.
Conclusion -
There are many causes of kidney allograft failure that are time-dependent. In addition, many diseases cause irreversible damage to the graft. An in-depth analysis of the causes of kidney allograft failure must consider these considerations. International efforts should be made to accurately collect clinical and histological parameters for kidney allograft failure. Getting a clear picture of the causes of graft failure is essential to develop better therapies or preventive measures in the future to improve life after kidney transplantation.
