Pharmacist-Driven CNI-Minimization Protocol to Preserve Renal Function Post-Liver Transplantation.

Abstract

Purpose: Preservation of renal function following orthotopic liver transplantation (OLT) through calcineurin inhibitor (CNI)-minimization is an established clinical objective. The use of everolimus (EVR) to reduce tacrolimus (TAC) exposure was recently shown to provide superior renal function 24 months post-OLT compared with patients on standard TAC therapy. Methods: We performed a retrospective cohort study of adult OLT recipients transplanted in 2013 who were placed on a CNI-minimization regimen (TAC trough goal 3-5 ng/mL) with EVR (goal trough 3-8 ng/mL). Clinical pharmacists prospectively identified patients based on eGFR (30-70 mL/min), absence of proteinuria (urine protein <500mg/day), total cholesterol <350 mg/dL, and fasting triglycerides <500 ng/dL. The primary endpoint was the change in renal function from CNI-minimization, as assessed by eGFR at 4 and 12 weeks post-conversion. Renal function was compared with a cohort of patients meeting the same criteria, who remained on standard TAC therapy (goal trough 6-10 mg/mL). Results: In total, 21 patients met criteria and 14 were converted to EVR. There were no differences in race, sex, CMV risk, hepatocellular carcinoma or primary diagnoses between groups, and there were no acute rejections in either arm. MELD, cold ischemic time, and creatinine at transplant were well matched. Median time to conversion was 113 days, and this was used as reference time in the control arm. Baseline eGFR was lower in the EVR arm (55.4 vs. 46.8 mL/min, p = 0.025) but was not significantly different following conversion.Figure: No Caption available.There was a significantly higher change in eGFR in week 4 and week 12 in the EVR conversion arm (-6.4 mL/min in the control arm vs +6.2 mL/min in the EVR arm, p = 0.021). No treatment-limiting adverse events occurred in either group through 12 weeks of follow-up. Conclusion: We note a significant improvement in renal function for patients on EVR compared to those on standard TAC, demonstrating successful implementation of pharmacist-driven CNI-minimization strategy following OLT. DISCLOSURES:Horwedel, T.: Speaker's Bureau, Novartis. Chapman, W.: Speaker's Bureau, Novartis.