{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:27:28Z","timestamp":1787808448923,"version":"build-2784847793"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"US Food and Drug Administration","award":["RO1 FD004826"],"award-info":[{"award-number":["RO1 FD004826"]}]},{"name":"Polycystic Kidney Disease Foundation"},{"DOI":"10.13039\/100000002","name":"National Institues of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Translational Science Award","award":["UL1TR002529-01"],"award-info":[{"award-number":["UL1TR002529-01"]}]},{"name":"Mayo Clinic Robert M. and Billie Kelley Pirnie Translational PKD Center"},{"name":"Diabetes and Digestive and Kidney Diseases","award":["P30DK090728"],"award-info":[{"award-number":["P30DK090728"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AR072581"],"award-info":[{"award-number":["AR072581"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["DK110871"],"award-info":[{"award-number":["DK110871"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["ULTR002529-01"],"award-info":[{"award-number":["ULTR002529-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Defense Peer Reviewed Medical Research Program","award":["W81XWH-16-PRMRP-IIRA"],"award-info":[{"award-number":["W81XWH-16-PRMRP-IIRA"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NIH-K23DK102824"],"award-info":[{"award-number":["NIH-K23DK102824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This Phase 1b cross-over study compared the safety of treatment with a low dose (15\u2009mg) of the peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3) agonist pioglitazone or placebo in PKD patients, with each treatment given for 1\u2009year. The study monitored known side effects of PPAR-\u03b3 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 \u03a9 [95% confidence interval\u2009(CI)\u20090.24\u20132.96], P\u2009=\u20090.024} 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 \u22123.5% (95% CI \u22128.4\u20131.4, P\u2009=\u20090.14), diastolic BP and microalbumin:creatinine ratio.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this small pilot trial in people with ADPKD but without diabetes, pioglitazone 15\u2009mg was found to be as safe as placebo. Larger and longer-term randomized trials powered to assess effects on TKV are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfaa232","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T16:13:56Z","timestamp":1603815236000},"page":"1738-1746","source":"Crossref","is-referenced-by-count":26,"title":["A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease"],"prefix":"10.1093","volume":"14","author":[{"given":"Bonnie L","family":"Blazer-Yost","sequence":"first","affiliation":[{"name":"Department of Biology, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Bacallao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, 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