Renal disease in the allograft recipient

Area of Science:

• Nephrology
• Transplantation Medicine
• Immunosuppression

Background:

• Chronic renal failure is more frequent after liver transplantation (LT) compared to other transplants, increasing mortality.
• Renal impairment can occur pre-LT, peri-operatively, or post-LT, with increasing incidence due to MELD allocation and higher-risk grafts.
• Calcineurin inhibitor (CNI) nephrotoxicity is a primary, modifiable cause of renal dysfunction post-LT.

Purpose of the Study:

• To evaluate strategies for preventing and managing CNI-associated nephrotoxicity after LT.
• To assess the impact of CNI minimization and alternative immunosuppressants on renal function.
• To determine the effectiveness of reducing CNI dosage and introducing mycophenolate mofetil (MMF) or everolimus in preserving kidney function.

Main Methods:

• Post-operative CNI minimization strategies, including induction therapy and delayed/reduced CNI introduction.
• Combination therapy with mycophenolate mofetil (MMF) or everolimus.
• Assessment of renal function (e.g., GFR) at various follow-up points.

Main Results:

• Everolimus allows drastic CNI minimization post-LT, leading to superior kidney function up to 3 years.
• Reducing CNI dose and introducing MMF upon renal impairment improves GFR within 6 months to 2 years with low rejection rates.
• Despite interventions, renal function often fails to normalize once estimated GFR (eGFR) drops below 60 ml/min/1.73m².

Conclusions:

• CNI minimization, particularly with everolimus, is a key strategy for preserving kidney function after LT.
• Early intervention with CNI reduction and MMF can improve renal function in patients with established impairment.
• Long-term renal recovery remains challenging for patients with significant pre-existing or CNI-induced kidney damage post-LT.