KIDNEY DISEASES 1 Review Iranian Journal of Kidney Diseases | Volume 11 | Number 1 | January 2017 Safety and Efficacy of Two Different Doses of Everolimus in Kidney Transplantation A Systematic Review and Meta-Analysis Morteza Arab-Zozani, 1 Mitra Mahdavi-Mazdeh, 2 Edris Hasanpoor, 3 Djavad Ghoddoosi Nejad, 4 Mobin Sokhanvar, 5 Edris Kakemam 6 Introduction. The aim of this systematic review and meta-analysis was to evaluate the efficacy-related events and adverse events of 2 different doses of everolimus in kidney transplant recipients. Materials and Methods. The Cochrane, PubMed, and Google Scholar databases were searched for randomized controlled trials published by the end of 2015 on the use of everolimus in kidney transplant recipients at doses of 1.5 mg/d and 3 mg/d. Two independent reviewers assessed the studies for quality and eligibility and extracted the data. The relative risk (RR) and 95% confidence interval (CI) for treated efficacy-related events and adverse events were collected to calculate pooled measures. Results. A total of 8 articles describing 7 randomized controlled trials (n = 2148 participants) were included in this study. The overall RR in adverse event outcomes was significantly in favor of the lower dose of everolimus (RR, 0.96; 0.95% CI, 0.93 to 0.99; P < .001). The overall risk of graft loss was lower with 1.5 mg/d of everolimus (RR, 0.76; 0.95% CI, 0.59 to 0.99; P = .04, I 2 = 25.0%). There was no relationship between the rates of efficacy failure, biopsy-proven acute rejection, death, or loss to follow up outcomes in all the three follow-up times between the two doses of everolimus. Conclusions. The result of this systematic review and meta-analysis showed that the overall outcomes in adverse events and graft loss were better with everolimus, 1.5 mg/d, than with everolimus, 3 mg/d, when combined with other kidney transplantation medications. IJKD 2017;11:1-11 www.ijkd.org 1 School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2 Tissue Bank and Research Center, Tehran University of Medical Sciences, Tehran, Iran 3 Social Determinants of Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran 4 Medical Informatics Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran 5 Health Services Management Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran 6 Iranian Center of Excellence in Health Management, School of management and medical informatics, Tabriz University of Medical Sciences, Tabriz, Iran Keywords. everolimus, adverse events, efficacy-related events, kidney transplantation INTRODUCTION Kidney transplantation is the treatment of choice for most patients with end-stage renal disease. 1,2 To reduce the risk of rejection, different regimens of immunosuppressive drugs are used. 3,4 Calcineurin inhibitors are linked to nephrotoxicity, hypertension, hyperlipidemia, and new-onset diabetes mellitus. 5,6 Thus, current efforts are focused on nonnephrotoxic immunosuppressive regimens that can reduce exposure to calcineurin inhibitors, while maintaining low rates of acute rejections. 2 Everolimus is a member of the mammalian target of rapamycin inhibitor class with comparable efficacy to mycophenolate mofetil when used with corticosteroids and standard-dose cyclosporine A. 7,8 Everolimus is a mammalian target of rapamycin inhibitor that is structurally similar to sirolimus, 3,4 but with a number of important pharmacokinetic differences, including a shorter half-life and time to steady state. 6,9 . Everolimus was previously approved in Europe for use in adult kidney and heart transplant recipients and in the United States in combination with reduced-dose calcineurin inhibitors and