{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:04:35Z","timestamp":1789538675574,"version":"build-2803163510"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for chronic kidney disease (CKD)-associated anemia. This study evaluated whether HIF-PHIs reduce red blood cell transfusion and intravenous iron exposure compared with placebo, standard care, or erythropoiesis-stimulating agents (ESAs) and assessed efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase, and Web of Science were systematically searched. Randomized controlled trials comparing an HIF-PHI with placebo, standard care, or an ESA in adults with CKD-associated anemia were eligible. The primary outcomes were red blood cell transfusion and intravenous iron exposure. Secondary outcomes included changes in hemoglobin, cardiovascular events, and all-cause mortality, while safety was assessed using adverse event outcomes. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Furthermore, the certainty of evidence was assessed using the GRADE framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 36 independent randomized controlled trials involving 27,680 participants with CKD-associated anemia were included. The trials evaluated six HIF-PHIs, namely, roxadustat, daprodustat, vadadustat, molidustat, enarodustat, and desidustat, against placebo, standard treatment or care, or an ESA. Compared with control interventions, HIF-PHIs significantly reduced the risk of any red blood cell transfusion (RR = 0.74, 95% CI: 0.58\u20130.93) and rescue red blood cell transfusion (RR = 0.70, 95% CI: 0.53\u20130.92). Intravenous iron outcomes generally favored HIF-PHIs, although neither the risk of any intravenous iron use (RR = 0.66, 95% CI: 0.38\u20131.14) nor the mean monthly intravenous iron dose (SMD = \u22120.19, 95% CI: \u22120.42 to 0.03) reached statistical significance, indicating residual uncertainty. Rates of major adverse cardiovascular events, all-cause mortality, and serious adverse events were not significantly increased with HIF-PHIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with CKD-associated anemia, HIF-PHIs improved hemoglobin without significantly increasing major adverse cardiovascular events, all-cause mortality, or serious adverse events; however, the small increase in any adverse event and the hyperkalemia signal in non-dialysis-dependent patients warrant attention. Together with the significant reduction in red blood cell transfusion and the possible reduction in intravenous iron use, these findings support HIF-PHIs as a promising oral treatment option. Longer follow-up and continued post-marketing surveillance are required to clarify long-term safety and effects across patient subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261387833<\/jats:ext-link>\n                      , Identifier CRD420261387833.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1916346","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:30:46Z","timestamp":1789536646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on transfusion and intravenous iron use in chronic kidney disease anemia: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiazheng","family":"Huang","sequence":"first","affiliation":[{"name":"Dongfang Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongfang Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dongfang Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awei","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongfang Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mianzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dongfang Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Tianjin Hospital of Integrated Traditional Chinese and Western Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsong","family":"Cao","sequence":"additional","affiliation":[{"name":"Dongfang Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/s41581-025-00934-5","article-title":"Advances and challenges in kidney fibrosis therapeutics","volume":"21","author":"Abbad","year":"2025","journal-title":"Nat. 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