Project 3: Regulation of renal perfusion and oxygenation in sepsis-induced acute kidney injury
Sepsis and septic shock constitute the most common causes of acute kidney injury (AKI) in intensive care patients and sepsis-induced AKI (SI-AKI) is fraught with high mortality. The pathophysiology behind SI-AKI remains unclear. Systemic hemodynamics vary (hyper- versus hypodynamic conditions), intrarenal hemodynamics and oxygenation have not been systematically studied. In accordance with the unifying hypothesis of the Research Unit, we hypothesize that local intrarenal hypoxia due to dysregulation of renal hemodynamics is a pivotal element in the pathophysiology of SIAKI, and that this relies on the renin-angiotensin system (RAS) and deranged intrarenal metabolism of nitric oxide (NO). Moreover, low-dose nitrite may alleviate SI-AKI. We have established methods to comprehensively characterize regulation of global renal as well as local cortical and medullary hemodynamics and oxygenation in rats. In rat models of contrast medium-induced AKI (CI-AKI), and renal ischemia/reperfusion injury, we found that intrarenal hypoxia is a key pathophysiological factor. Intriguingly, low-dose nitrite administration alleviated CI-AKI. The objectives of this proposal are 1) to comprehensively characterize regulation of renal hemodynamics and oxygenation in two rat models of SI-AKI, 2) to elucidate the role of the RAS, and 3) to test whether low-dose nitrite alleviates SI-AKI.
*Dr. Arakelyan left the institution in December 2014.