biostudies-literatureOfori-Acquah SFNHLBI NIH HHSNIGMS NIH HHS1044-1048https://www.ebi.ac.uk/biostudies/studies/S-EPMC7218735biostudies-literatureUnknown135(13)Acute kidney injury (AKI) is a major clinical concern in sickle cell disease (SCD). Clinical evidence suggests that red cell alarmins may cause AKI in SCD, however, the sterile inflammatory process involved has hitherto not been defined. We discovered that hemopexin deficiency in SCD is associated with a compensatory increase in α-1-microglobulin (A1M), resulting in an up to 10-fold higher A1M-to-hemopexin ratio in SCD compared with healthy controls. The A1M-to-hemopexin ratio is associated with markers of hemolysis and AKI in both humans and mice with SCD. Studies in mice showed that excess heme is directed to the kidneys in SCD in a process involving A1M causing AKI, whereas excess heme in controls is transported to the liver as expected. Using genetic and bone marrow chimeric tools, we BloodHemopexin deficiency promotes acute kidney injury in sickle cell disease.PMC7218735K01 HL133331R01 GM113816U54 HL141011Paintsil VLenhart DOwusu-Dabo ECrosby DOfori-Acquah SFHazra RVitturi DAGhosh SOrikogbo OOTan RJFlage BSickleGenAfrica NetworkAckah EBfalseHemopexin deficiency promotes acute kidney injury in sickle cell disease.Acute kidney injury (AKI) is a major clinical concern in sickle cell disease (SCD). Clinical evidence suggests that red cell alarmins may cause AKI in SCD, however, the sterile inflammatory process involved has hitherto not been defined. We discovered that hemopexin deficiency in SCD is associated with a compensatory increase in α-1-microglobulin (A1M), resulting in an up to 10-fold higher A1M-to-hemopexin ratio in SCD compared with healthy controls. The A1M-to-hemopexin ratio is associated with markers of hemolysis and AKI in both humans and mice with SCD. Studies in mice showed that excess heme is directed to the kidneys in SCD in a process involving A1M causing AKI, whereas excess heme in controls is transported to the liver as expected. Using genetic and bone marrow chimeric tools, we 2020-01-01T00:00:00Z2020 Mar2025-04-04T23:50:26.685Z2025-04-04T23:50:26.685ZS-EPMC72187353204311210.1182/blood.2019002653