A randomized, prospective comparison of transition to sirolimus-based CNI-minimization or withdrawal in African American kidney transplant recipients

Clin Transplant. 2016 May;30(5):528-33. doi: 10.1111/ctr.12718. Epub 2016 Mar 14.

Abstract

Background: There is a lack of conclusive evidence to suggest if calcineurin inhibitor (CNI) withdrawal or minimization with sirolimus is the best strategy for African Americans.

Methods: This was a randomized, prospective, open-label, pilot study comparing the two mammalian target of rapamycin (mTOR) transition strategies in adult African Americans between six and 24 wk post-transplant. The primary outcome was a comparison of the eGFR at one yr after conversion.

Results: Forty patients were randomized and analyzed in an intent-to-treat fashion. Median day of transition was day 96 (withdrawal) and 68 (minimization). Patients in the CNI-withdrawal group (n = 23) had significantly higher eGFR at one yr compared to the CNI-minimization group (n = 17, 73 vs. 56 mL/min, p = 0.03), as well as a significantly larger increase in eGFR from baseline (12 vs. 5 mL/min, p = 0.03). There were no differences in infections, acute rejection, death, or graft loss. Both regimens were constrained by disproportionately high discontinuation rates despite modest toxicity profiles.

Conclusion: In spite of considerable withdrawal rate across both study arms, African American kidney transplant recipients who underwent early transition to a sirolimus-based CNI-withdrawal regimen had significantly better graft function at one yr compared to those transitioned to a sirolimus-based CNI-minimization regimen. Clinicaltrials.gov identifier: NCT01005706.

Keywords: kidney; mammalian target of rapamycin; minimization; transplant; withdrawal.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black or African American
  • Calcineurin Inhibitors*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / epidemiology*
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Pilot Projects
  • Postoperative Complications*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Sirolimus / therapeutic use*
  • Transplant Recipients
  • United States / epidemiology
  • Withholding Treatment*

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT01005706