{"doi":"10.1093/ckj/sfaa232","title":"A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease","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.","journal":"Clinical Kidney Journal","year":2020,"id":105185,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":416204,"name":"Robert L. Bacallao","orcid":"0000-0002-5703-5701","position":1,"is_corresponding":false},{"id":247457,"name":"Bradley J. Erickson","orcid":"0000-0001-7926-6095","position":2,"is_corresponding":false},{"id":333034,"name":"Michelle LaPradd","orcid":null,"position":3,"is_corresponding":false},{"id":330187,"name":"Marie E. Edwards","orcid":null,"position":4,"is_corresponding":false},{"id":510726,"name":"Nehal Sheth","orcid":null,"position":5,"is_corresponding":false},{"id":510727,"name":"Kim Swinney","orcid":null,"position":6,"is_corresponding":false},{"id":510728,"name":"Kristen Ponsler-Sipes","orcid":null,"position":7,"is_corresponding":false},{"id":307591,"name":"Ranjani N. Moorthi","orcid":"0000-0002-3125-0868","position":8,"is_corresponding":false},{"id":450756,"name":"Susan M. Perkins","orcid":"0000-0002-5842-4354","position":9,"is_corresponding":false},{"id":232142,"name":"Vicente E. Torres","orcid":"0000-0003-2008-1576","position":10,"is_corresponding":false},{"id":307588,"name":"Sharon M. Moe","orcid":"0000-0003-3562-9725","position":11,"is_corresponding":false},{"id":509590,"name":"Bonnie L. Blazer‐Yost","orcid":"0000-0002-1899-4555","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:12:17.683386Z","pmid":"34221381","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}