Everolimus and long-term decline in renal function after liver transplantation: real-life experience with measured GFR

Abstract

Switching from calcineurin-inhibitors (CNI) to everolimus >6–12-months after liver transplantation (LT) seems inefficient in improving renal function, but whether everolimus halts further renal-function decline compared to low-dose CNI remains unclear. In a retrospective single-center study of everolimus after LT (2008–2016) with routine measured glomerular filtration rates (mGFR; ⁵¹Cr-EDTA- or iohexol clearance), we compared by propensity-score matching everolimus therapy to low-dose CNI therapy. The study comprised 36 patients with everolimus introduced on average 22 months post-LT (range 2–105 months, median follow-up 3.4 years), and 36 matched controls. Everolimus introduction was associated with a mean improvement in mGFR of 7 mL/min up to 1 year (p = .003), restricted to patients switched <1-year post-transplant and at tacrolimus trough levels >5 ng/mL. The differences between the everolimus group and controls in delta-mGFR from baseline to 1 year (7.3 vs 4.3 mL/min, p = .25) or 1-year to last follow-up (−0.8 vs −0.2 mL/min/year, p = .71) were non-significant. Proportions with mGFR decline >3 mL/min/year were similar between groups (11% and 14%, p = 1.00). Everolimus was stopped in three patients (8%), and acute rejection occurred in 17%. In conclusion, despite an early improvement in renal function after everolimus introduction, we found no evidence that everolimus halts the long-term mGFR decline compared to continued low-dose CNI therapy. Due to retrospective design, small sample size and heterogenous characteristics, definite conclusions require prospective studies.

Keywords:

• mTOR
• tacrolimus
• calcineurin inhibitor
• kidney disease

Disclosure statement

No potential conflict of interest was reported by the author(s).

Grants and financial support

FÅ received a research grant from Stiftelsen för Transplantations- och Cancerforskning.

Author contributions

F.Å. designed the study; J.B. and F.Å. collected the data and analyzed the data and wrote the first draft; G.H., M.C. and W.B. reviewed the manuscript and gave critical comments. All authors approved the final manuscript.