{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:14:10Z","timestamp":1785795250690,"version":"3.56.0"},"reference-count":81,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in sickle cell disease (SCD). Anemia, induced by chronic persistent hemolysis, is associated with the progressive deterioration of renal health, resulting in CKD. Moreover, patients with SCD experience acute kidney injury (AKI), a risk factor for CKD, often during vaso-occlusive crisis associated with acute intravascular hemolysis. However, the mechanisms of hemolysis-driven pathogenesis of the AKI-to-CKD transition in SCD remain elusive. Here, we investigated the role of increased renovascular rarefaction and the resulting substantial loss of the vascular endothelial protein C receptor (EPCR) in the progressive deterioration of renal function in transgenic SCD mice. Multiple hemolytic events raised circulating levels of soluble EPCR (sEPCR), indicating loss of EPCR from the cell surface. Using bone marrow transplantation and super-resolution ultrasound imaging, we demonstrated that SCD mice overexpressing EPCR were protective against heme-induced CKD development. In a cohort of patients with SCD, plasma sEPCR was significantly higher in individuals with CKD than in those without CKD. This study concludes that multiple hemolytic events may trigger CKD in SCD through the gradual loss of renovascular EPCR. Thus, the restoration of EPCR may be a therapeutic target, and plasma sEPCR can be developed as a prognostic marker for sickle CKD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023023528","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T20:56:45Z","timestamp":1717189005000},"page":"552-564","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Heme-induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-6740","authenticated-orcid":false,"given":"Qiyang","family":"Chen","sequence":"first","affiliation":[{"name":"1Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rimi","family":"Hazra","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Crosby","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Lenhart","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane C.","family":"Lenhart","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paritosh","family":"Mondal","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingze","family":"Zhang","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"},{"name":"3Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7465-0581","authenticated-orcid":false,"given":"Seyed M.","family":"Nouraie","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"},{"name":"3Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick J.","family":"Tan","sequence":"additional","affiliation":[{"name":"4Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles T.","family":"Esmon","sequence":"additional","affiliation":[{"name":"5Coagulation Biology Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2099-0585","authenticated-orcid":false,"given":"L. Vijay Mohan","family":"Rao","sequence":"additional","affiliation":[{"name":"6Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-1135","authenticated-orcid":false,"given":"Kang","family":"Kim","sequence":"additional","affiliation":[{"name":"1Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA"},{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"},{"name":"7Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3536-3077","authenticated-orcid":false,"given":"Samit","family":"Ghosh","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Pittsburgh Heart, Lung, and Blood Vascular 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