Variability of the Mammalian Target of Rapamycin Inhibitors Is Correlated With Long-Term Renal Graft Survival

Transplant Proc. 2019 Mar;51(2):341-343. doi: 10.1016/j.transproceed.2018.08.016. Epub 2018 Sep 5.

Abstract

Background: Many studies demonstrate the relationship between the high intrapatient variability of calcineurin inhibitor (CNI) levels and poor long-term renal graft outcome. Our objective is to analyze the intrapatient variability observed in the mammalian target of rapamycin inhibitors (mTOR-i) blood levels, to compare the variability of sirolimus (SRL) with that of everolimus (EVL) in kidney transplant patients converted to an mTOR-i, and to analyze whether the coefficient of variation (CV) was correlated with long-term graft survival.

Methods: We analyzed 279 adult renal transplant patients converted to an mTOR-i. CV was calculated using at least 3 blood trough levels between 3 and 18 months postconversion.

Results: The mean and median CV of the entire group was 25.54% and 23.7%, respectively. SRL and EVL mean CV was 23.8% and 27.1% (P = .03), respectively. The group of patients into the last tertile with CV> 28.52% presented a lower death-censored graft survival (75.26% vs. 93.01%, P < .0001) with a mean follow-up of 66.5 months.

Conclusion: The CV of mTOR-i is correlated with long-term renal graft survival, so it should be considered a prognostic factor. SRL has a lower CV than EVL in renal transplant patients converted to mTOR-i in the stable posttransplant phase.

MeSH terms

  • Adult
  • Calcineurin Inhibitors / blood
  • Calcineurin Inhibitors / therapeutic use
  • Everolimus / blood
  • Everolimus / therapeutic use*
  • Female
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Sirolimus / blood
  • Sirolimus / therapeutic use*

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • Sirolimus