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

Scand J Gastroenterol. 2020 Jun;55(6):718-724. doi: 10.1080/00365521.2020.1770328. Epub 2020 Jun 1.

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: calcineurin inhibitor; kidney disease; mTOR; tacrolimus.

MeSH terms

  • Adult
  • Aged
  • Calcineurin Inhibitors / pharmacology
  • Everolimus / adverse effects*
  • Everolimus / therapeutic use
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects*
  • Graft Rejection
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Kidney / drug effects
  • Kidney / physiopathology*
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Retrospective Studies

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus