Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta-analysis of randomized trials

Nephrology (Carlton). 2014 Apr;19(4):217-26. doi: 10.1111/nep.12211.


Aim: 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.

Conclusion: 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.

Keywords: TORC inhibitors; meta-analysis; polycystic kidney disease; somatostatin analogues; vasopressin receptor antagonists.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Disease Progression
  • Humans
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Molecular Targeted Therapy
  • Polycystic Kidney, Autosomal Dominant / diagnosis
  • Polycystic Kidney, Autosomal Dominant / drug therapy*
  • Polycystic Kidney, Autosomal Dominant / physiopathology
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / physiopathology
  • Renal Insufficiency / prevention & control*
  • Time Factors
  • Treatment Outcome
  • Urological Agents / adverse effects
  • Urological Agents / therapeutic use*


  • Urological Agents