“Mycophenolate‐Based Immunosuppression After Calcineurin‐Inhibitor Withdrawal in Liver Transplant Recipients is Safe and Results in Long‐Term Improvement in Renal Function”

Introduction Renal dysfunction is an important side effect of calcineurin inhibitors (CNI) and is associated with worse outcomes after liver transplantation (LT). Prior studies on mycophenolate‐based (MMF), CNI‐free immunosuppression regimens have raised concerns about the risk of rejection (ACR). We evaluated the long‐term impact of transition from CNI to MMF‐based immunosuppression on long‐term renal function and other clinical outcomes. Methods We performed a single‐center, retrospective review of LT recipients from 1/1/2008 to 12/31/2021 who were transitioned from CNI‐ to MMF‐based immunosuppression for renal dysfunction. Primary outcome was mean change in eGFR at 1‐ and 5‐years after CNI withdrawal: a sequential stratification model was then used to compare changes in eGFR to a control group comprising patients maintained on CNIs at last follow‐up date. Secondary outcomes included first episode of acute cellular rejection (ACR), graft survival and patient survival. Results Fifty‐one patients were switched to a MMF‐based immunosuppression regimen at median time of 29.1 months after LT and were then followed for median 93.2 months. Mean age at time of LT was 57.5 years old, 41 (80.4%) patients were male, 44 (86.3%) patients were white and 16 (32.7%) patients had a history of hepatitis C. Model‐based estimates of the increase in eGFR‐CKD‐Epi were 5.7 (95% CI: 2.4, 9.0, p = 0.001) mL/min per 1.73 m 2 and 10.2 (95% CI: 5.0, 15.3, p < 0.001) mL/min per 1.73 m 2 between baseline and 1‐year and between baseline and 5‐years after CNI withdrawal. On multivariable analysis, CNI withdrawal was not associated with an increased risk of ACR (HR 2.22, 95% CI (0.79, 6.23), p = 0.13). Conclusions The use of MMF‐based immunosuppression after CNI withdrawal results in long‐term improvement in renal function without significantly increasing the risk of ACR. As more LT recipients present with and develop renal dysfunction in the post‐MELD era, conversion to a MMF‐based immunosuppression to preserve kidney function is both safe and effective.