Dominguez, Jesus H.Xie, DanhuiDominguez, James M., 2ndKelly, K. J.2024-05-232024-05-232022-11Dominguez, J. H., Xie, D., Dominguez, J. M., & Kelly, K. J. (2022). Role of coagulation in persistent renal ischemia following reperfusion in an animal model. American Journal of Physiology - Renal Physiology, 323(5), F590–F601. https://doi.org/10.1152/ajprenal.00162.2022https://hdl.handle.net/1805/40999Ischemic acute kidney injury is common, deadly, and accelerates the progression of chronic kidney disease, yet has no specific therapy. After ischemia, reperfusion is patchy with early and persistent impairment in regional renal blood flow and cellular injury. We tested the hypothesis that intrarenal coagulation results in sustained renal ischemia following reperfusion, using a well-characterized model. Markedly decreased, but heterogeneous, microvascular plasma flow with microthrombi was found postischemia by intravital microscopy. Widespread tissue factor expression and fibrin deposition were also apparent. Clotting was accompanied by complement activation and inflammation. Treatment with exosomes derived from renal tubular cells or with the fibrinolytic urokinase, given 24 h postischemia when renal failure was established, significantly improved microvascular flow, coagulation, serum creatinine, and histological evidence of injury. These data support the hypothesis that intrarenal clotting occurs early and the resultant sustained ischemia is a critical determinant of renal failure following ischemia; they demonstrate that the coagulation abnormalities are amenable to therapy and that therapy results in improvement in both function and postischemic inflammation. NEW & NOTEWORTHY Ischemic renal injury carries very high morbidity and mortality, yet has no specific therapy. We found markedly decreased, heterogeneous microvascular plasma flow, tissue factor induction, fibrin deposition, and microthrombi after renal ischemia-reperfusion using a well-characterized model. Renal exosomes or the fibrinolytic urokinase, administered after renal failure was established, improved microvascular flow, coagulation, renal function, and histology. Data demonstrate that intrarenal clotting results in sustained ischemia amenable to therapy that improves both function and postischemic inflammation.en-USPublisher Policyacute kidney injuryexosomesfibrinolysisischemia-reperfusionmicrovasculatureArticle