Blazer-Yost, Bonnie L.Bacallao, Robert L.Erickson, Bradley J.LaPradd, Michelle L.Edwards, Marie E.Sheth, NehalSwinney, KimPonsler-Sipes, Kristen M.Moorthi, Ranjani N.Perkins, Susan M.Torres, Vicente E.Moe, Sharon M.2023-02-032023-02-032021-07Blazer-Yost BL, Bacallao RL, Erickson BJ, et al. A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease. Clin Kidney J. 2021;14(7):1738-1746. Published 2021 Jan 26. doi:10.1093/ckj/sfaa232https://hdl.handle.net/1805/31137Background: 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 {mean difference 0.16 Ω [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 15 mg was found to be as safe as placebo. Larger and longer-term randomized trials powered to assess effects on TKV are needed.en-USAttribution-NonCommercial 4.0 InternationalAnti-hypertensiveCrossover designMRIPPARγAgonistsTotal kidney volumeArticle