Background: Nephrotoxic side effects of calcineurin inhibitors (CNI) have been well established. The addition of anti-metabolites (AM) to CNI-based immunosuppression (IS) regimens has been proposed to lower CNI levels and mitigate nephrotoxic effects of CNI. The purpose of this study was to determine the outcomes of liver transplant recipients receiving a CNI-based regimen that included an AM compared with those who did not receive an anti-metabolite (No-AM).

Methods: We performed a single-center, retrospective study of 748 liver transplants between January 1, 2001 and June 30, 2012. The No-AM group (n=196) received CNI and steroids only whereas the AM group (n=552) received mycophenolate mofetil in addition to CNI and steroids. Patient and graft survival, CNI levels, rejection rates, infection rates and percent change in glomerular filtration rate (GFR) were compared at 1 and 3 years after transplant. Cox proportional hazards and Kaplan-Meier analyses were performed to assess potential risk factors.

Results: At 1 and 3 years after transplant, mean Tacrolimus (TAC) levels were significantly lower in the AM vs. No-AM group (AM: 6.0±3.3 and 5.2±2.6; No-AM: 7.4±3.5 and 6.2±3.4 respectively; p<0.001), rejection rates were significantly lower in the AM versus No-AM group (AM 35% and 39%; No-AM: 45% and 49%; p=0.02), and there were no differences in the infection rates between the AM and No-AM groups (AM 74% and 82%; No-AM: 73% and 86%; p=0.50). The AM group experienced a 35% increase in GFR above pre-transplant baseline at 1 and 3 years, while the No-AM group demonstrated a significant 12% and 14% decrease in GFR at the same time points after transplant (p<0.001). Graft survival was significantly lower at 1 and 3 years after transplant in the AM group versus the No-AM group (AM 89% and 81%; No-AM: 89% and 85%; p=0.04). Despite the poorer graft survival, there was no difference in overall patient survival between the two groups at 1 and 3 years (AM 92% and 85%; No-AM: 93% and 89%; p=0.054).

Conclusion: In this cohort of liver transplant patients, the inclusion of AM in an IS regimen that includes CNI and steroids is associated with a significant reduction in TAC levels, improved renal function, lower rejection rates, and no increase in infection rates at 1 and 3 years after liver transplant. Further analysis is necessary to delineate the effect on graft survival.

CITATION INFORMATION: Karim A, Conway D, Leverson G, Mezrich J, Fernandez L, D'Alessandro A, Foley D. Adding an Antimetabolite to a Calcineurin-Inhibitor-Based Immunosuppression Regimen Leads to Improved Native Renal Function After Liver Transplantation. Am J Transplant. 2016;16 (suppl 3).

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