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

Abstract

BackgroundConversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach.ObjectivesTo investigate the benefits and harm from randomized clinical trials (RCTs) involving the conversion from CNI to everolimus after kidney transplantation.MethodsDatabases 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).ResultsEleven 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.ConclusionsConversion 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.

Factors Contributing to Kidney Allograft Loss and Associated Consequences among Post Kidney Transplantation Patients

“…The recipient's immune characteristics as well as posttransplant immunosuppressive drugs such as Tacrolimus and mycophenolate mofetil are considered as the greatest risk factors for BK Viral Nephropathy (BKVN) onset [74,75] that causes graft loss in renal transplant. Patients post kidney transplantation is prone to severe infections.…”

De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients: A trial-based linkage study

“…The rate of discontinuation of study drug within our study was, however, comparable to rates published in other studies. 6,10,22,28,32 Finally, the majority of the participants were of Caucasian race, therefore the results may not be generalizable to other racial groups.…”

“…The earliest meta-analysis of mTORI demonstrated no significant difference in the risk of cancer, however all trials had less than 2 years of follow-up and did not report on NMSC outcomes. 28 Two larger meta-analyses of mTORI with aggregate data 26 and individual-patient-data 29 showed a reduction in NMSC by approximately 50%. 28 Two larger meta-analyses of mTORI with aggregate data 26 and individual-patient-data 29 showed a reduction in NMSC by approximately 50%.…”

“…30 A more recent meta-analysis of conversion from CNI to everolimus did not demonstrate any benefit with respect to overall cancer risk. 28 Two larger meta-analyses of mTORI with aggregate data 26 and individual-patient-data 29 showed a reduction in NMSC by approximately 50%. These findings are similar to our results in the RD-CNI arm, where we found a similar reduction in NMSC risk.…”

Urologic malignancies in kidney transplantation

“…Another meta‐analysis found a significant cancer risk reduction for skin cancer and a modest reduction for renal cancers . While mTOR inhibitors may be associated with decreased risk of posttransplantation malignancy and have been used to treat advanced RCC in the nontransplantation setting, more data are needed as equipoise about the use of mTOR inhibitors in the setting of RCC remains …”