Metabolic and Renal Effects of Mammalian Target of Rapamycin Inhibitors Treatment After Liver Transplantation: Real-Life Single-Center Experience

Transplant Proc. 2021 Jan-Feb;53(1):221-227. doi: 10.1016/j.transproceed.2020.05.021. Epub 2020 Jul 7.

Abstract

Background: Mammalian target of rapamycin (mTOR) inhibitors following liver transplantation (LT) are used to minimize calcineurin inhibitor (CNI)-related nephrotoxicity. Data about metabolic effects of mTOR inhibitors are still limited.

Aim: This study aims to determine the renal and metabolic effects of different mTOR inhibitor-based protocols in real-life LT patients.

Methods: This is a retrospective cohort study of patients treated with mTOR inhibitors after LT. Demographics, treatment protocols, glomerular filtration rate (GFR), and metabolic parameters were collected over a period of 4 years. Initiation of blood pressure (BP), diabetes mellitus, and lipid medications was also noted.

Results: Fifty-two LT recipients received mTOR inhibitors. GFR improved significantly (by 1.96 mL/min/year), with greater improvement in patients with baseline renal dysfunction (+13.3 mL/min vs +4.5 mL/min at 3 years). Conversion to an mTOR inhibitor during the first post-transplant year resulted in a more durable improvement in GFR (for 4 years vs only 1 year for later conversion).No significant weight gain or new-onset diabetes mellitus was observed. However, there was some increase in total cholesterol (+7 mg/dL) and blood pressure (+2 mm Hg during the third year and +8 mm Hg in the fourth years), followed by initiation of lipid-lowering and BP medications in 25% and 13% of patients, respectively.

Conclusions: Treatment with an mTOR inhibitor following LT resulted in improved kidney functions without significant negative metabolic effects such as weight gain or new-onset diabetes mellitus. This makes mTOR inhibitors a valuable immunosuppressive option in the face of the growing incidence of nonalcoholic steatohepatitis as a leading cause for LT.

MeSH terms

  • Aged
  • Calcineurin Inhibitors / adverse effects
  • Cohort Studies
  • Everolimus / therapeutic use*
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / drug effects
  • Kidney Diseases / epidemiology
  • Kidney Diseases / etiology
  • Kidney Diseases / prevention & control
  • Liver Transplantation* / adverse effects
  • Male
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / etiology
  • Middle Aged
  • Postoperative Complications / epidemiology
  • Postoperative Complications / etiology
  • Postoperative Complications / prevention & control*
  • Retrospective Studies
  • Sirolimus / therapeutic use*

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • Sirolimus