Conversion to everolimus in liver transplant patients with renal dysfunction

Transplant Proc. 2011 Jul-Aug;43(6):2307-10. doi: 10.1016/j.transproceed.2011.06.009.

Abstract

Calcineurin inhibitor (CNI) immunosuppressive therapy post-liver transplantation (OLT) is important to reduce graft rejection episodes. However, these drugs show important side effects, particularly renal dysfunction (RDF). Changing from CNI to a nonnephrotoxic drug, as mammalian target of rapamycin (mTOR) inhibitor may solve the problem. Our objective was to evaluate renal function (RF) among liver transplant patients initially receiving CNI, among whom the patients with RDF were converted completely or partially to an mTOR inhibitor like everolimus (EVE). We performed a prospective study in liver transplant patients from 2000 to 2009. Creatinine levels and creatinine clearances (Cockroft-Gault) expressed as mean values ± standard deviations were measured pre- and postswitch for comparisons using Wilcoxon nonparametric tests. Six patients were converted fully or partially to EVE. Their mean age at the moment of introducing the new therapy was 52.2 ± 13.6 years (range = 28-60). Immunosuppression time prior to switching from CNI to EVE was 23.8 ± 26.6 months (range = 6-70). Postconversion follow-up was 25.8 ± 16.5 months (range = 8-42). All patients showed improvement in RF. The creatinine level improvement was significant (P = .03) namely, from a mean of 2.26 ± 0.49 to 1.21 ± 0.57 mg/dL. Glomerular filtration rate improved from a mean of 40 ± 15.13 to 72.60 ± 17.3 mL/min/m(2) (P = .03). Conversion from CNI to EVE improved creatinine concentrations and creatinine clearances with long-term effects free of graft rejection.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Calcineurin Inhibitors
  • Chile
  • Creatinine / blood
  • Drug Substitution
  • Drug Therapy, Combination
  • Everolimus
  • Female
  • Glomerular Filtration Rate / drug effects
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / physiopathology
  • Liver Transplantation* / adverse effects
  • Liver Transplantation* / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • Recovery of Function
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • Creatinine
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus