What are the causes of kidney transplant failure?

Causes of Kidney Transplant Failure

Kidney transplant failure can result from multiple etiologies including acute and chronic rejection, vascular complications, recurrent disease, medication toxicity, and traditional risk factors for chronic kidney disease. 1

Timing-Related Causes of Transplant Failure

Immediate Post-Transplant Period (<1 week)

• Acute tubular necrosis (ATN) - most common cause of early intrinsic dysfunction, especially in deceased donor kidneys 1, 2
• Renal artery or vein thrombosis - typically results from technical surgical difficulties or clotting disorders 1
• Early surgical failure requiring graft nephrectomy 1

Early Post-Transplant Period (1 week to 1 month)

• Acute rejection - cellular or antibody-mediated 1
• Vascular complications - renal artery stenosis, pseudoaneurysm formation 1
• Peritransplant fluid collections - hematomas, lymphoceles, urinomas 1

Intermediate Post-Transplant Period (1-3 months)

• Calcineurin inhibitor toxicity - most common during drug titration period 1
• Acute rejection episodes - particularly in under-immunosuppressed patients 3
• BK polyomavirus nephropathy - requiring immunosuppression reduction 1

Late Post-Transplant Period (>3 months)

• Chronic rejection - most common cause of late graft dysfunction 1, 3
• Recurrent glomerular disease 1, 4
• Development of donor-specific antibodies (DSAs) - often associated with medication non-adherence 5
• Interstitial fibrosis/tubular atrophy (IFTA) 1

Immunological Causes of Transplant Failure

Acute Rejection

• Cellular rejection - T-cell mediated damage to the allograft 1
• Antibody-mediated rejection (ABMR) - caused by donor-specific antibodies 5
• Multiple or late acute rejection episodes significantly increase risk of chronic rejection 3

Chronic Rejection

• Progressive deterioration in graft function starting at least 3 months post-transplant 3
• Characterized by specific histological findings on biopsy 3
• Often preceded by one or more acute rejection episodes 3

Sensitization and Antibody Development

• Development of donor-specific antibodies (DSAs) 1, 5
• Sensitization following immunosuppression reduction or withdrawal 1
• Graft intolerance syndrome (GIS) - chronic inflammatory state due to immunological intolerance of the failed allograft 1

Non-Immunological Causes of Transplant Failure

Vascular Complications

• Renal artery stenosis (RAS) - can lead to progressive graft dysfunction 1
• Renal artery or vein thrombosis - often results in early graft loss 1
• Arteriovenous fistula (AVF) formation - can occur post-biopsy 1

Medication-Related Issues

• Calcineurin inhibitor nephrotoxicity - particularly with supratherapeutic levels 1
• Medication non-adherence - especially problematic in adolescent recipients 5
• Inappropriate immunosuppression management during allograft functional decline 1

Traditional Risk Factors for CKD Progression

• Hypertension, proteinuria, anemia, dyslipidemia 4
• Diabetes and bone mineral disorders 4
• Donor and recipient age - older donor age associated with worse outcomes 4
• Time on dialysis before transplantation 4

Infectious Complications

• BK polyomavirus nephropathy 1
• Opportunistic infections related to immunosuppression 6
• Sepsis requiring reduction in immunosuppression 1

Management Considerations for Failing Allografts

Immunosuppression Management

• Balancing the risk of rejection versus infection/malignancy 1
• Consideration of future transplantation candidacy when tapering immunosuppression 1
• Maintenance of residual renal function when possible 1

Surgical Management

• Transplant nephrectomy for hemorrhage, unrelenting pain, malignancy, or persistent sepsis 1
• Embolization as an alternative to nephrectomy in selected cases 1
• Timing of nephrectomy based on inflammatory state and future transplant plans 1

Pitfalls and Caveats

• Failing to recognize medication non-adherence as a major cause of rejection and graft loss, particularly in younger recipients 5
• Inappropriate immunosuppression reduction leading to sensitization and decreased chances for future transplantation 1
• Overlooking traditional CKD risk factors in transplant recipients that contribute to graft loss 4
• Delaying transplant nephrectomy in cases of severe graft intolerance syndrome, which can lead to increased morbidity 1
• Failing to balance the benefits of residual renal function against the risks of continued immunosuppression in a failing allograft 1