Efficacy and safety of mTOR inhibitor therapy in patients with early-stage autosomal dominant polycystic kidney disease: a meta-analysis of randomized controlled trials.
BACKGROUND
The objective of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) to present a profound review and an objective appraisal of the efficacy and safety of the mammalian target of rapamycin (mTOR) inhibitor therapy in patients with autosomal dominant polycystic kidney disease (ADPKD).


METHODS
RCTs involving the mTOR inhibitor therapy in patients with ADPKD are included. The data of studies and major outcomes include changes in patients' glomerular filtration rate (GFR), urinary protein, total kidney volume (TKV), cyst volume, parenchymal volume, and lipid profile and the frequency of adverse events. Review Manager 5.0 for meta-analysis was used in this study.


RESULTS
Up to January 31, 2011, 4 RCTs (with a total of 564 patients) were included. The mTOR inhibitor therapy group had smaller TKV than the control group [weighted mean difference (WMD) of TKV after treatment: -318.45, P = 0.04]. The mTOR inhibitor treatment does not necessarily slow down the aggravation of renal function in patients with ADPKD (WMD of GFR after therapy: 5.55, P < 0.01; at 6-month analyses = -0.97, P = 0.56). Side effects could occur during the mTOR inhibitor therapy, but the severities can be controlled by the appropriate use of drug.


CONCLUSIONS
Based on the current limited clinical trials, this study suggests that short-duration mTOR inhibitor therapy is relatively safe to slow down the increase in kidney volume in patients with early-stage ADPKD, but it has limited impact on slowing down the decrease in GFR.
Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Qiang
Q
He
Chiayu
C
Lin
Shunxian
S
Ji
Jianghua
J
Chen
D000068338:Everolimus; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000473:pathology; D008055:Lipids / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D008055:Lipids; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus