Transplantation proceedings · 2014
Sirolimus for treatment of autosomal-dominant polycystic kidney disease: a meta-analysis of randomized controlled trials.
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Liu Y-M, Shao Y Q, He Q
Аннотация
BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is the most common form of cystic kidney disease. The mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling but plays an uncertain role in the treatment of ADPKD. The objective of our study was to conduct a meta-analysis of randomized controlled trials (RCTs) to present an objective appraisal of the efficacy and safety of sirolimus therapy in patients with ADPKD.
METHODS: We conducted a meta-analysis of RCTs performed in adults with ADPKD, and compared the effect of sirolimus on total kidney volume (TKV), glomerular filtration rate (GFR), cyst volume, and daily urinary protein excretion. Safety was evaluated based on analysis of blood pressure, lipid profile, complete blood count, infection, and other reported adverse events.
RESULTS: Four RCTs were included. The sirolimus therapy group had smaller TKV than the control group. The mean difference (MD) of TKV post-treatment compared with the control group was -234.74 (P = .01). However, GFR did not reach a statistically significant difference between groups. Standard mean difference (SMD) of GFR after therapy was 0.24 (95% confidence interval [CI], 0.05-0.52; P = .11), but sirolimus seemed to increase urine protein excretion (P = .002). There was no statically significant difference in leukocytes, hemoglobin, platelets, and blood pressure between groups. Aphthous stomatits and pharyngitis are reported more commonly in the sirolimus therapy group compared with the control group (P < .000001).
CONCLUSIONS: In ADPKD patients, treatment with sirolimus is safe and can effectively slow kidney growth, but it seems not to slow down the decrease of GFR.
METHODS: We conducted a meta-analysis of RCTs performed in adults with ADPKD, and compared the effect of sirolimus on total kidney volume (TKV), glomerular filtration rate (GFR), cyst volume, and daily urinary protein excretion. Safety was evaluated based on analysis of blood pressure, lipid profile, complete blood count, infection, and other reported adverse events.
RESULTS: Four RCTs were included. The sirolimus therapy group had smaller TKV than the control group. The mean difference (MD) of TKV post-treatment compared with the control group was -234.74 (P = .01). However, GFR did not reach a statistically significant difference between groups. Standard mean difference (SMD) of GFR after therapy was 0.24 (95% confidence interval [CI], 0.05-0.52; P = .11), but sirolimus seemed to increase urine protein excretion (P = .002). There was no statically significant difference in leukocytes, hemoglobin, platelets, and blood pressure between groups. Aphthous stomatits and pharyngitis are reported more commonly in the sirolimus therapy group compared with the control group (P < .000001).
CONCLUSIONS: In ADPKD patients, treatment with sirolimus is safe and can effectively slow kidney growth, but it seems not to slow down the decrease of GFR.