A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease
dc.contributor.author | Blazer-Yost, Bonnie L. | |
dc.contributor.author | Bacallao, Robert L. | |
dc.contributor.author | Erickson, Bradley J. | |
dc.contributor.author | LaPradd, Michelle L. | |
dc.contributor.author | Edwards, Marie E. | |
dc.contributor.author | Sheth, Nehal | |
dc.contributor.author | Swinney, Kim | |
dc.contributor.author | Ponsler-Sipes, Kristen M. | |
dc.contributor.author | Moorthi, Ranjani N. | |
dc.contributor.author | Perkins, Susan M. | |
dc.contributor.author | Torres, Vicente E. | |
dc.contributor.author | Moe, Sharon M. | |
dc.contributor.department | Biology, School of Science | en_US |
dc.date.accessioned | 2023-02-03T15:31:25Z | |
dc.date.available | 2023-02-03T15:31:25Z | |
dc.date.issued | 2021-07 | |
dc.description.abstract | 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 {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_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Blazer-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/sfaa232 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/31137 | |
dc.language.iso | en_US | en_US |
dc.publisher | Oxford University Press | en_US |
dc.relation.isversionof | 10.1093/ckj/sfaa232 | en_US |
dc.relation.journal | Clinical Kidney Journal | en_US |
dc.rights | Attribution-NonCommercial 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | Anti-hypertensive | en_US |
dc.subject | Crossover design | en_US |
dc.subject | MRI | en_US |
dc.subject | PPARγ | en_US |
dc.subject | Agonists | en_US |
dc.subject | Total kidney volume | en_US |
dc.title | A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease | en_US |
dc.type | Article | en_US |