Efficacy and Safety of Everolimus for Maintenance Immunosuppression of Kidney Transplantation: A Meta-Analysis of Randomized Controlled Trials

PLoS One. 2017 Jan 20;12(1):e0170246. doi: 10.1371/journal.pone.0170246. eCollection 2017.

Abstract

Background: Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach.

Objectives: To investigate the benefits and harm from randomized clinical trials (RCTs) involving the conversion from CNI to everolimus after kidney transplantation.

Methods: Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).

Results: Eleven RCTs, with a total of 1,633 patients, met the final inclusion criteria. Patients converted to everolimus had improved renal function at 1 year posttransplant with an estimated glomerular filtration rate (eGFR) of 5.36 mL/min per 1.73 m2 greater than patients remaining on CNI (p = 0.0005) and the longer-term results (> 1 year) of renal function was identical to that of 1 year. There was not a substantial difference in graft loss, mortality, and the occurrence of adverse events (AEs) or serious AEs. However, the risks of acute rejection and trial termination due to AEs with everolimus are respectively 1.82 and 2.63 times greater than patients staying on CNI at 1 year posttransplant (p = 0.02, p = 0.03, respectively). Further, those patients who converted to everolimus had a substantially greater risk of anemia, hyperlipidemia, hypercholesterolemia, hypokalemia, proteinuria, stomatitis, mouth ulceration, and acne.

Conclusions: Conversion from CNI to everolimus after kidney transplantation is associated with improved renal function in the first 5 years posttransplant but increases the risk of acute rejection at 1 year posttransplant and may not be well endured.

Publication types

  • Meta-Analysis

MeSH terms

  • Everolimus / administration & dosage*
  • Graft Rejection
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Randomized Controlled Trials as Topic*

Substances

  • Immunosuppressive Agents
  • Everolimus

Grants and funding

This research was funded by Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (Grant No. 2016A016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.