{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:09:09Z","timestamp":1790154549524,"version":"4.0.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00351399"],"award-info":[{"award-number":["RS-2024-00351399"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-21082988"],"award-info":[{"award-number":["RS-2025-21082988"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Hypothesis<\/jats:title>\n                    <jats:p>Hepatic ischemia-reperfusion (HIR) injury often extends beyond the primary site and causes damage in distant organs, including the kidney. In particular, concomitant kidney injury accompanying liver injury represents a significant clinical problem, but this mechanistic understanding remains unclear. Given that the liver is the primary organ responsible for clearing cytotoxic cell-free hemoglobin (CFH) and heme released during hemolysis, we hypothesized that hemolysis and impaired hepatic clearance of these hemolysis-derived products following HIR may contribute to kidney injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were subjected to HIR, after which liver and kidney injury were evaluated. Some mice were administered with cilastatin, a blocker of megalin, or deferoxamine, an iron chelator and ferroptosis inhibitor. After HIR, hemolysis, hepatic expression of CFH\/heme clearance-related genes, and ferroptosis in the kidney were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HIR induced liver and kidney damage, accompanied by hemolysis, increased CFH\/heme levels, and reduced levels of haptoglobin and hemopexin, key regulators of hepatic CFH\/heme clearance, in the liver. HIR caused hemoglobin internalization into proximal tubule cells (PTCs). Furthermore, HIR increased heme oxygenase-1 expression, iron content, and lipid peroxidation in the kidneys, while decreasing glutathione levels, indicating that HIR induces ferroptosis in PTCs. Cilastatin prevented HIR-induced hemoglobin uptake, iron accumulation, and lipid peroxidation in the kidneys, thereby protecting the kidneys. Deferoxamine also protected the kidneys against HIR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that HIR-induced remote kidney injury (RKI) is associated with elevated circulating CFH\/heme resulting from impaired hepatic CFH\/heme clearance and increased hemolysis. This suggests that CFH\/heme act as mediators of HIR-induced RKI, and that targeting hemolysis and CFH\/heme cytotoxicity may be a strategy to treat and prevent remote organ injury, particularly in the kidneys.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfag190","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:24:54Z","timestamp":1787570694000},"source":"Crossref","is-referenced-by-count":0,"title":["Hepatic injury-induced remote kidney injury is associated with impaired hepatic clearance of cell-free hemoglobin"],"prefix":"10.1093","author":[{"given":"Yong Kwon","family":"Han","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medicine, Kyungpook National University , 680 Gukchaebosang-ro, Junggu, Daegu ,","place":["Republic of Korea"]},{"name":"Cardiovascular Research Institute, Kyungpook National University , 680 Gukchaebosang-ro, Junggu, Daegu ,","place":["Republic of 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