A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease

Bonnie L. Blazer-Yost, Robert L. Bacallao, Bradley J. Erickson, Michelle L. LaPradd, Marie E. Edwards, Nehal Sheth, Kim Swinney, Kristen M. Ponsler-Sipes, Ranjani N. Moorthi, Susan M. Perkins, Vicente E. Torres, Sharon M. Moe

Research output: Contribution to journalArticlepeer-review


Background. Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenetic disorders in humans and is characterized by numerous fluid-filled cysts that grow slowly, resulting in end-stage renal disease in the majority of patients. Preclinical studies have indicated that treatment with low-dose thiazolidinediones, such as pioglitazone, decrease cyst growth in rodent models of PKD. Methods. This Phase 1b cross-over study compared the safety of treatment with a low dose (15 mg) of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone or placebo in PKD patients, with each treatment given for 1 year. The study monitored known side effects of PPAR-γ agonist treatment, including fluid retention and edema. Liver enzymes and risk of hypoglycemia were assessed throughout the study. As a secondary objective, the efficacy of low-dose pioglitazone was followed using a primary assessment of total kidney volume (TKV), blood pressure (BP) and kidney function. Results. Eighteen patients were randomized and 15 completed both arms. Compared with placebo, allocation to pioglitazone resulted in a significant decrease in total body water as assessed by bioimpedance analysis fmean difference 0.16 X [95% confidence interval (CI) 0.24-2.96], P=0.024} and no differences in episodes of heart failure, clinical edema or change in echocardiography. Allocation to pioglitazone led to no difference in the percent change in TKV of -3.5% (95% CI -8.4-1.4, P=0.14), diastolic BP and microalbumin:creatinine ratio. Conclusions. In this small pilot trial in people with ADPKD but without diabetes, pioglitazone 15mg was found to be as safe as placebo. Larger and longer-term randomized trials powered to assess effects on TKV are needed.

Original languageEnglish (US)
Pages (from-to)1738-1746
Number of pages9
JournalClinical Kidney Journal
Issue number7
StatePublished - Jul 1 2021


  • MRI
  • PPARc
  • agonists
  • anti-hypertensive
  • crossover design
  • total kidney volume

ASJC Scopus subject areas

  • Nephrology
  • Transplantation


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