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.
Highlights
Kidney transplantation is the treatment of choice for most patients with end-stage renal disease
Results are expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI)
Patients converted to everolimus had improved renal function at 1 year posttransplant with an estimated glomerular filtration rate of 5.36 mL/min per 1.73 m2 greater than patients remaining on calcineurin inhibitor (CNI) (p = 0.0005) and the longer-term results (> 1 year) of renal function was identical to that of 1 year
Summary
Kidney transplantation is the treatment of choice for most patients with end-stage renal disease. The calcineurin inhibitors (CNIs) are the principal components of immunosuppressive therapy after kidney transplantation and have made a major contribution to current long-term transplant outcomes[1, 2]. CNIs are associated with a number of potentially serious side effects, including nephrotoxicity, diabetes, hypertension, and neurotoxicity that contribute to morbidity and mortality after transplantation [4,5,6,7,8]. Combined therapy with tacrolimus and mycophenolic acid may be associated with a higher risk of BK infection [9], which is the significant and dangerous factor in the failure of the transplanted kidney. Diminishing or even eliminating CNI has become the focus of further optimization of immunosuppressive therapy in renal transplantation. Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach
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