Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

Ann Transplant. 2015 Nov 26:20:707-13. doi: 10.12659/aot.895320.

Abstract

Background: Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients.

Material/methods: Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months.

Results: Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6-8.7 mL/min, p<0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion.

Conclusions: Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects*
  • Cohort Studies
  • Everolimus / administration & dosage
  • Everolimus / adverse effects
  • Female
  • Follow-Up Studies
  • Germany
  • Graft Rejection
  • Graft Survival
  • Hospitals, University
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Kidney Failure, Chronic / drug therapy
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / mortality
  • Kidney Function Tests
  • Linear Models
  • Liver Transplantation / adverse effects
  • Liver Transplantation / methods*
  • Liver Transplantation / mortality
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Retrospective Studies
  • Risk Assessment
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Survival Rate
  • TOR Serine-Threonine Kinases / administration & dosage
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Time Factors
  • Transplantation Immunology
  • Treatment Outcome

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • TOR Serine-Threonine Kinases
  • Sirolimus