Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta-analysis of randomized trials.
OBJECTIVE
Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta-analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume (TKV) and renal function in ADPKD.


METHODS
Relevant trials were identified, and outcomes were: change in TKV, total cyst volume (TCV), renal function and adverse events. Meta-analysis used random effects, with results expressed as mean difference and risk ratio both with 95% confidence intervals (CI).


RESULTS
Eleven trials (2262 patients) were included. Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5 trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06) or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9% (95% CI -10.33 to -7.58%) but did not alter eGFR. The vasopressin receptor antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI -3.48 to -2.52) and slowed kidney function decline over a 3-year period. A single trial (n = 41) of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or renal dysfunction (P = 0.78). Adverse events were significant for interventions in all trials compared with placebo.


CONCLUSIONS
These data suggest that somatostatin analogues and vasopressin receptor antagonists attenuate TKV increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to heterogeneity in study population, drug efficacy and follow-up duration. In the future, further well-designed and powered trials of longer duration using new biomarkers or therapeutic agents with better tolerance are required.
Department of Renal Medicine and Transplantation, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia.
Thida M
TM
Myint
Gopi K
GK
Rangan
Angela C
AC
Webster
D018450:Disease Progression; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D064804:Urological Agents / Q000009:adverse effects / Q000627:therapeutic use*
D064804:Urological Agents
TORC inhibitors; meta-analysis; polycystic kidney disease; somatostatin analogues; vasopressin receptor antagonists