{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:54:39Z","timestamp":1791269679590,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>The aim of this systematic review and network meta\u2010analysis was to clarify the risk of acute kidney injury (AKI) and acute heart failure associated with hypoxia\u2010inducible factor\u2013prolyl hydroxylase inhibitors (HIF\u2010PHIs) in patients with anemia of chronic kidney disease. The certainty of evidence for each outcome was assessed using the Confidence in Network Meta\u2010Analysis approach. The primary outcomes were AKI and acute heart failure, while the secondary outcome was any kidney injury. Thirty\u2010five studies, performed between 2009 and 2025, were included in the network meta\u2010analysis. HIF\u2010PHIs were associated with a higher risk of AKI compared with erythropoiesis\u2010stimulating agents (ESAs) (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.02\u20131.47, moderate certainty) and placebo (RR 1.40, 95% CI 1.11\u20131.75, high certainty). HIF\u2010PHIs were also associated with an increased risk of any kidney injury compared with placebo (RR 1.13, 95% CI 1.01\u20131.26, moderate certainty). ESAs ranked lower in terms of acute heart failure risk than both HIF\u2010PHIs and placebo, although the differences were not statistically significant. Vadadustat (RR 0.30, 95% CI 0.12\u20130.74, moderate certainty) and ESAs (RR 0.40, 95% CI 0.17\u20130.94, high certainty) were associated with a lower risk of acute heart failure compared with placebo. In conclusion, HIF\u2010PHIs may be associated with an increased incidence of AKI compared with placebo and ESAs. In contrast, vadadustat and ESAs might be associated with a decreased incidence of acute heart failure compared with placebo. Further robust studies should be conducted to validate these findings.<\/jats:p>","DOI":"10.1002\/cpt.70516","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:46:40Z","timestamp":1791269200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute Kidney Injury and Heart Failure Risk with Hypoxia\u2010Inducible Factor\u2013Prolyl Hydroxylase Inhibitors: A Network Meta\u2010Analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-1253","authenticated-orcid":false,"given":"Satoru","family":"Mitsuboshi","sequence":"first","affiliation":[{"name":"Department of Pharmacy Kaetsu Hospital  Niigata Japan"},{"name":"Division of Drug Informatics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Morizumi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Ohno Memorial Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-613X","authenticated-orcid":false,"given":"Shungo","family":"Imai","sequence":"additional","affiliation":[{"name":"Division of Drug Informatics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4596-5418","authenticated-orcid":false,"given":"Satoko","family":"Hori","sequence":"additional","affiliation":[{"name":"Division of Drug Informatics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-1177","authenticated-orcid":false,"given":"Kazumasa","family":"Kotake","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Zikei Hospital\/Zikei Institute of Psychiatry  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_12_1_1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/ckj\/sfab195","article-title":"Contemporary outcomes of anemia in US patients with chronic kidney disease","volume":"15","author":"Wittbrodt E.T.","year":"2022","journal-title":"Clin. 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