Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response

Deuel, J W; Schaer, C A; Boretti, F S; Opitz, L; Garcia-Rubio, I; Baek, J H; Spahn, D R; Buehler, P W; Schaer, D J

doi:10.1038/cddis.2015.392

Citations

Citation copied

Deuel, J. W., Schaer, C. A., Boretti, F. S., Opitz, L., Garcia-Rubio, I., Baek, J. H., Spahn, D. R., Buehler, P. W., & Schaer, D. J. (2016). Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response. Cell Death and Disease, 7, e2064. https://doi.org/10.1038/cddis.2015.392

Abstract

Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe(2+)) to ferric Hb(Fe(3+)), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tis