What is the approach to managing a failing kidney graft?

Management of a Failing Kidney Graft

The management of a failing kidney graft requires a coordinated shared-care model between transplant centers and general nephrologists, with immunosuppression weaning tailored to individual patient factors including candidacy for re-transplantation and residual graft function. 1

Definition of Failing Allograft

A failing kidney allograft can be defined as:

• Stable but low allograft function (CKD stage 4-5)
• Progressive decline in kidney function with anticipated allograft survival <1 year
• Return to renal replacement therapy 1

Assessment and Monitoring

• Monitor eGFR closely when <30 ml/min/1.73m²
• Consider referral for vascular access planning when eGFR <20 ml/min/1.73m² 2
• Review all medications for nephrotoxicity and adjust dosages according to renal function 2
• Target BP <130/80 mmHg using appropriate agents (ACEi/ARBs if stable function, calcium channel blockers) 2

Immunosuppression Management Strategy

The approach to immunosuppression should be based on:

1. Candidacy for re-transplantation
2. Presence of residual renal function
3. Risk of infection and malignancy

For Patients Eligible for Re-transplantation:

• Maintain low-dose immunosuppression to prevent sensitization if re-transplantation is anticipated within 1 year 1
• Consider tapering in the following order:
  1. Anti-proliferative agents (MMF, AZA) first
  2. Calcineurin inhibitors (CNI) next, maintaining low therapeutic trough levels
  3. Prednisone last, with slow tapering over 6 months 1

For Patients Not Eligible for Re-transplantation:

• With residual function: Consider maintaining minimal immunosuppression to preserve function
• Without residual function (anuric): Taper and discontinue all immunosuppression 1

Managing Complications

Graft Intolerance Syndrome (GIS)

• Monitor for signs of pain over graft site, hematuria, fever
• Consider transplant nephrectomy if severe symptoms develop after immunosuppression withdrawal 1

Infection Risk

• Patients with failed allografts on immunosuppression have significantly higher rates of infection (88% vs 38%) 1
• Consider prophylaxis against cytomegalovirus and pneumocystis pneumonia 1
• Avoid prolonged use of hemodialysis catheters; prefer AV fistula to reduce infection risk 3

Malignancy Risk

• Certain cancers (Kaposi sarcoma, non-Hodgkin's lymphoma, lip cancer) decrease after return to dialysis
• Others (leukemia, lung, kidney, urinary tract, thyroid cancers) remain elevated 1
• Consider complete withdrawal of immunosuppression in patients with history of skin cancers 1

Preparation for Renal Replacement Therapy

• Educate patients about all renal replacement options (hemodialysis, peritoneal dialysis, transplantation)
• Consider peritoneal dialysis to maintain residual kidney function 2
• For re-transplantation candidates, evaluate and list when graft survival is anticipated to be <1 year 1
• Educate about living donor transplantation and kidney-paired donation options 1

Special Considerations

• Belatacept: Limited data on withdrawal strategies; requires individualized approach 4
• Avoid conversion from CNI-based to belatacept-based maintenance regimen in stable kidney transplant recipients unless CNI intolerant, due to increased risk of acute rejection 4

Common Pitfalls to Avoid

• Delayed referral for re-transplantation evaluation
• Abrupt discontinuation of immunosuppression (risk of GIS)
• Continuing full immunosuppression in anuric patients not eligible for re-transplantation (increased infection risk)
• Inadequate monitoring for opportunistic infections during immunosuppression withdrawal
• Poor communication between transplant centers and general nephrologists during transition of care 1

The management of failing kidney allografts remains challenging due to limited high-quality evidence. A coordinated approach between specialists with careful immunosuppression management tailored to individual patient factors offers the best chance for improved outcomes and reduced morbidity in this vulnerable patient population.