Efficacy And Safety Of MTOR Inhibitor For Early-stage ADPKD Patients: A Meta-analysis Of Randomized Controlled Trials

Purpose:The objective of this study is to conduct a meta-analysis of the randomized controlled trials (RCT) to make a profound review and an objective appraisal of the effectiveness and safety of the mammalian target of rapamycin (mTOR) inhibitor therapy in autosomal dominant polycystic kidney disease (ADPKD) patients.Methods:Relevant papers are searched. After thorough reviews, randomized controlled trials (RCTs) regarding the mTOR inhibitor therapy in ADPKD patients are included. The data of studies and major outcomes include the changes of patients' Glomerular Filtration Rate (GFR), urinary protein, total kidney volume (TKV), cyst volume (CV), parenchymal volume (PV), blood pressure, lipid profile and the frequency of adverse events. The Review Manager5.0 for meta-analysis is the software applied in this study.Results:Up to January 31st 2011,4 RCTs (568 patients) are included in this study. The meta-analysis made in this study indicates that mTOR inhibitor therapy group had smaller TKV than the control group, WMD of TKV after treatment is-302.08 (P=0.04), and also less increasing of TKV (WMD=-70.25, P<0.00001), CV (WMD=-35.91, P<0.00001) and PV (WMD=-34.84, P<0.00001). Also mTOR inhibitor treatment doesn't necessarily slow down the aggravation of renal function for ADPKD patients. WMD of GFR after therapy is 5.47 (P=0.001), but analyses in 6 months shows WMD =-0.97, (P=0.55). Side effects like hyperlipidemia, myelosuppression, abnormal liver function, diarrhea, rash, aphthous stomatitis could occur during the mTOR inhibitor therapy, but the severities can be controlled by the appropriate use of drug.Conclusions:Based on the current very limited clinical trials, mTOR inhibitor is a relatively safe drug to slow down the kidney volume growth in ADPKD patients, especially in the parenchymal tissues, but have limited impact on slowing down the decrease of renal function.