{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T06:07:50Z","timestamp":1749794870705,"version":"3.37.3"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","award":["CSH-2022-A-002"],"award-info":[{"award-number":["CSH-2022-A-002"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>There is limited information on the efficacy of pioglitazone in diabetic kidney diseases (DKD). We evaluated whether pioglitazone exerts renal-protective effects in DKD patients. We designed a retrospective cohort study, which included 742 type 2 diabetes mellitus (T2DM) patients with DKD in Taiwan, with eGFR between 30 and 90 ml\/min\/1.73 m<jats:sup>2<\/jats:sup>and UACR level 300\u20135000 mg\/g. Patients not meeting the target range for HbA1c (above 7%) were given additional medication with pioglitazone (n = 111) or received standard care (non-pioglitazone group, n = 631). The primary endpoint was the occurrence of composite renal endpoints, which was defined as sustained eGFR&lt;15 ml\/min\/1.73 m<jats:sup>2<\/jats:sup>(confirmed by two measurements within 90 days); doubling of serum creatinine (compared to baseline); and the presence of hemodialysis or renal transplantation. The median follow-up duration was two years. At baseline, the mean HbA1C levels in the pioglitazone and non-pioglitazone groups were 8.8% and 8.1%, respectively; mean ages were 64.4 and 66.2 years old, respectively; diabetes durations were 14.3 and 12.3 years, respectively. Baseline eGFR showed no significant difference between the pioglitazone and non-pioglitazone groups (55.8 and 58.8 mL\/min\/1.73 m<jats:sup>2<\/jats:sup>, respectively). In terms of gender, 63% of patients were male in the pioglitazone group compared with 57% in the non-pioglitazone group. Pioglitazone use did not reduce the risk of composite renal endpoints in DKD patients (HR: 0.97, 95% CI = 0.53\u20131.77), including persistent eGFR&lt;15 ml\/min\/1.73 m<jats:sup>2<\/jats:sup>(HR = 1.07, 95% CI = 0.46\u20132.52), doubling of serum creatinine (HR = 0.97, 95% CI = 0.53\u20131.77), or ESRD (HR = 2.58, 95% CI = 0.29\u201323.04). The results were not changed after various adjustments. A non-significant albuminuria reduction was also noted after pioglitazone prescription in DKD patients. Further randomized controlled studies are needed to establish the effects of pioglitazone definitively.<\/jats:p>","DOI":"10.1371\/journal.pone.0264129","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T18:34:10Z","timestamp":1645122850000},"page":"e0264129","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["The efficacy of pioglitazone for renal protection in diabetic kidney disease"],"prefix":"10.1371","volume":"17","author":[{"given":"Chao-Chung","family":"Ho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Sun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Ning","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Chang","family":"Lo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Hsun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-5467","authenticated-orcid":true,"given":"Edy","family":"Kornelius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"pone.0264129.ref001","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas","volume":"157","author":"P Saeedi","year":"2019","journal-title":"Diabetes research and clinical practice"},{"key":"pone.0264129.ref002","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.pop.2020.08.004","article-title":"Diabetic Kidney Disease.","volume":"47","author":"R Bonner","year":"2020","journal-title":"Primary Care: Clinics in Office Practice"},{"issue":"24","key":"pone.0264129.ref003","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1056\/NEJMoa0802743","article-title":"Effects of intensive glucose lowering in type 2 diabetes","volume":"358","author":"Action to Control Cardiovascular Risk in Diabetes Study Group","year":"2008","journal-title":"N Engl J Med"},{"key":"pone.0264129.ref004","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1053\/ajkd.2000.16225","article-title":"Preserving renal function in adults with hypertension and diabetes: a consensus approach","volume":"36","author":"GL Bakris","year":"2000","journal-title":"American journal of kidney diseases"},{"key":"pone.0264129.ref005","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"SP Marso","year":"2016","journal-title":"New England Journal of Medicine"},{"key":"pone.0264129.ref006","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"V Perkovic","year":"2019","journal-title":"New England Journal of Medicine"},{"key":"pone.0264129.ref007","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"HJ Heerspink","year":"2020","journal-title":"New England Journal of Medicine"},{"key":"pone.0264129.ref008","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1089\/ars.2016.6664","article-title":"Diabetes and kidney disease: role of oxidative stress.","volume":"25","author":"JC Jha","year":"2016","journal-title":"Antioxidants & redox signaling"},{"key":"pone.0264129.ref009","doi-asserted-by":"crossref","first-page":"749","DOI":"10.3390\/cells8070749","article-title":"Dicarbonyl stress at the crossroads of healthy and unhealthy aging","volume":"8","author":"C Nigro","year":"2019","journal-title":"Cells"},{"key":"pone.0264129.ref010","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0140-6736(10)60576-4","article-title":"Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial","volume":"376","author":"F Ismail-Beigi","year":"2010","journal-title":"The Lancet"},{"key":"pone.0264129.ref011","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.2337\/dc11-0175","article-title":"Observation on renal outcomes in the Veterans Affairs Diabetes Trial","volume":"34","author":"L Agrawal","year":"2011","journal-title":"Diabetes care"},{"key":"pone.0264129.ref012","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.3390\/ijms19072063","article-title":"Maintenance of kidney metabolic homeostasis by PPAR gamma","volume":"19","author":"P Corrales","year":"2018","journal-title":"International journal of molecular sciences"},{"key":"pone.0264129.ref013","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1053\/j.ajkd.2009.11.013","article-title":"Effect of thiazolidinediones on albuminuria and proteinuria in diabetes: a meta-analysis","volume":"55","author":"PA Sarafidis","year":"2010","journal-title":"American Journal of Kidney Diseases"},{"key":"pone.0264129.ref014","doi-asserted-by":"crossref","first-page":"109346","DOI":"10.1016\/j.biopha.2019.109346","article-title":"Pioglitazone downregulates Twist-1 expression in the kidney and protects renal function of Zucker diabetic fatty rats","volume":"118","author":"Z Wang","year":"2019","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"pone.0264129.ref015","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1210\/clinem\/dgz252","article-title":"Pioglitazone for the primary and secondary prevention of cardiovascular and renal outcomes in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis.","volume":"105","author":"Y Zhou","year":"2020","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"pone.0264129.ref016","doi-asserted-by":"crossref","first-page":"e0129922","DOI":"10.1371\/journal.pone.0129922","article-title":"Thiazolidinediones and risk of long-term dialysis in diabetic patients with advanced chronic kidney disease: a nationwide cohort study","volume":"10","author":"YH Chen","year":"2015","journal-title":"PloS one"},{"key":"pone.0264129.ref017","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00592-017-0983-0","article-title":"Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus","volume":"54","author":"YH Chang","year":"2017","journal-title":"Acta diabetologica"},{"key":"pone.0264129.ref018","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.2337\/diabetes.49.6.1022","article-title":"Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats","volume":"49","author":"K Isshiki","year":"2000","journal-title":"Diabetes"},{"key":"pone.0264129.ref019","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1093\/ndt\/gfn157","article-title":"Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats","volume":"23","author":"GJ Ko","year":"2008","journal-title":"Nephrology Dialysis Transplantation"},{"key":"pone.0264129.ref020","doi-asserted-by":"crossref","first-page":"e79815","DOI":"10.1371\/journal.pone.0079815","article-title":"SUMOylation of PPAR\u03b3 by rosiglitazone prevents LPS-induced NCoR degradation mediating down regulation of chemokines expression in renal proximal tubular cells","volume":"8","author":"Y Lu","year":"2013","journal-title":"PloS one."},{"key":"pone.0264129.ref021","doi-asserted-by":"crossref","first-page":"62641","DOI":"10.1155\/2007\/62641","article-title":"Peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3) agonists attenuate the profibrotic response induced by TGF-\u03b21 in renal interstitial fibroblasts","volume":"2007","author":"W Wang","year":"2007","journal-title":"Mediators of inflammation"},{"key":"pone.0264129.ref022","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.2337\/db05-1285","article-title":"Thiazolidinediones ameliorate diabetic nephropathy via cell cycle\u2013dependent mechanisms","volume":"55","author":"T Okada","year":"2006","journal-title":"Diabetes"},{"key":"pone.0264129.ref023","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.amjmed.2015.03.025","article-title":"The diabetes shared care program and risks of cardiovascular events in type 2 diabetes","volume":"128","author":"E Kornelius","year":"2015","journal-title":"The American Journal of Medicine"},{"key":"pone.0264129.ref024","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.4158\/EP-2020-0143","article-title":"Dipeptidyl-Peptidase 4 Inhibitors did not Improve Renal Endpoints in Advanced Diabetic Kidney Disease","volume":"26","author":"E Kornelius","year":"2020","journal-title":"Endocrine Practice"},{"issue":"Suppl 1","key":"pone.0264129.ref025","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.2337\/dc19-S006","article-title":"Glycemic Targets: Standards of Medical Care in Diabetes-2019","volume":"42","author":"American Diabetes Association","year":"2019","journal-title":"Diabetes Care"},{"key":"pone.0264129.ref026","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/S0140-6736(05)67528-9","article-title":"Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial","volume":"366","author":"JA Dormandy","year":"2005","journal-title":"The Lancet"},{"key":"pone.0264129.ref027","doi-asserted-by":"crossref","first-page":"183108","DOI":"10.1155\/2008\/183108","article-title":"PPARgamma in Kidney Physiology and Pathophysiology","volume":"2008","author":"E Kiss-T\u00f3th","year":"2008","journal-title":"PPAR Res"},{"key":"pone.0264129.ref028","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/S0140-6736(06)69420-8","article-title":"Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial","volume":"368","author":"DT Investigators","year":"2006","journal-title":"The Lancet"},{"key":"pone.0264129.ref029","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1111\/j.1463-1326.2008.00892.x","article-title":"Pioglitazone and cardiovascular risk. A comprehensive meta\u2010analysis of randomized clinical trials","volume":"10","author":"E Mannucci","year":"2008","journal-title":"Diabetes, Obesity and Metabolism"},{"key":"pone.0264129.ref030","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1001\/archinternmed.2010.207","article-title":"Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality","volume":"170","author":"SE Nissen","year":"2010","journal-title":"Archives of internal medicine"},{"key":"pone.0264129.ref031","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1001\/archinte.164.19.2097","article-title":"A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors","volume":"164","author":"E Chiquette","year":"2004","journal-title":"Archives of Internal Medicine"},{"key":"pone.0264129.ref032","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1056\/NEJMoa1506930","article-title":"Pioglitazone after ischemic stroke or transient ischemic attack","volume":"374","author":"WN Kernan","year":"2016","journal-title":"N engl J med"},{"key":"pone.0264129.ref033","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1161\/CIRCULATIONAHA.117.030458","article-title":"Pioglitazone prevents stroke in patients with a recent transient ischemic attack or ischemic stroke: a planned secondary analysis of the IRIS trial (Insulin Resistance Intervention After Stroke)","volume":"137","author":"S Yaghi","year":"2018","journal-title":"Circulation"},{"key":"pone.0264129.ref034","doi-asserted-by":"crossref","first-page":"e0170874","DOI":"10.1371\/journal.pone.0170874","article-title":"The impact of renin-angiotensin system blockade on renal outcomes and mortality in pre-dialysis patients with advanced chronic kidney disease","volume":"12","author":"YJ Oh","year":"2017","journal-title":"PloS one"},{"key":"pone.0264129.ref035","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1053\/j.ajkd.2020.08.003","article-title":"SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: Report of a scientific workshop sponsored by the National Kidney Foundation","volume":"77","author":"KR Tuttle","year":"2021","journal-title":"American Journal of Kidney Diseases"},{"key":"pone.0264129.ref036","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/dom.12652","article-title":"Revitalization of pioglitazone: the optimum agent to be combined with a sodium\u2010glucose co\u2010transporter\u20102 inhibitor","volume":"18","author":"R DeFronzo","year":"2016","journal-title":"Diabetes, Obesity and Metabolism"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264129","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T17:46:57Z","timestamp":1700243217000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264129"}},"subtitle":[],"editor":[{"given":"Petter","family":"Bjornstad","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,17]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264129","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2022,2,17]]}}}