• Betty Pat, Joo-Yeun Oh, Juan Xavier Masjoan Juncos, Pamela C Powell, James F Collawn, Rakesh P Patel, Louis J Dell'Italia, and Clinical Working Group.
• Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham (UAB) Cardiovascular Institute, University of Alabama at Birmingham, Birmingham, Ala.
• J. Thorac. Cardiovasc. Surg. 2022 Dec 1; 164 (6): e289e308e289-e308.

ObjectiveHemolysis, characterized by formation of free hemoglobin (Hb), occurs in patients undergoing cardiopulmonary bypass (CPB). However, there is no study of the dynamic changes in red blood cell (RBC)-derived exosomes (Exos) released during CPB, nor whether these particles mediate acute kidney injury (AKI).MethodsThis study is a comprehensive time-course analysis, at baseline, 30 minutes, to 24 hours post-crossclamp release (XCR) to determine (1) Exos Hb content; (2) free Hb/heme, haptoglobin, hemopexin; and (3) urinary markers of AKI over the same time period. In addition, we developed a model system in Sprague-Dawley rats to test for AKI after intravenous injection of Exos Hb released during CPB.ResultsIn 30 patients undergoing CPB, there is a significant increase in plasma Hb-positive Exos but not microvesicles 30 minutes post-XCR versus other time points, with a simultaneous decrease in the haptoglobin/Hb ratio. These changes presage a significant increase in urine neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 at 24 hours. Intravenous injection of plasma Exos (109-10 particles obtained 30 minutes post-XCR) into rats causes AKI at 72 hours, manifested by multifocal degeneration of proximal tubular epithelium. At 21 days, there is persistent tubular injury and interstitial fibrosis. Intravenous injection of Exos from 35-day-old stored RBCs into rats results in glomerular-tubular injury, increased kidney ferritin and hemoxygenase-1 expression, and significant elevation of kidney injury molecule-1 and proteinuria at 72 hours.ConclusionsThese combined studies raise the potential for RBC-derived Exos, released during CPB, to target the kidney and mediate AKI.Published by Elsevier Inc.

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