Renal ischemia-reperfusion : early detection of kidney lesions and strategies of nephroprotection ; Ischémie-reperfusion rénale : dépistage précoce de lésions rénales et stratégies de néphroprotection

Renal ischemia-reperfusion is the consequence of everyday clinical situations and pathologies frequently encountered in medicine. Despite these various etiologies, the pathophysiology of further renal injuries is ultimately common to them all, with severe deleterious short- and long-term consequences. Understanding this common pathophysiology is therefore still essential to improve early diagnosis of ischemia-reperfusion injuries and their consequences in nephrology, notably acute kidney injury and renal failure, as well as to propose innovative therapies to ensure nephroprotection. My thesis investigated a nephroprotective strategy using mild therapeutic hypothermia (core body temperature at 34°C) in several mouse models of renal ischemia-reperfusion. We were able to demonstrate short- and long-term protection of renal function and histological structure, mitochondrial function, and systemic and renal inflammation. In parallel, we identified Cold-induced RNA-binding protein (CIRP) as correlated with kidney dysfunction and injuries. We proposed its use as a biomarker of acute kidney injury in a cohort of patients with global ischemia-reperfusion after a resuscitated cardiac arrest. Finally, we developed and refined new non-invasive imaging methods to assess renal performance in our mouse models of renal ischemia-reperfusion: renal artery ultrasound-doppler (vascular resistance), contrast-enhanced ultrasound (perfusion), photoacoustic imaging (tissue oxygenation). Thanks to these techniques, we were able to detect early alterations in these parameters after renal ischemia-reperfusion, which made it also possible to predict the persistence of chronic alterations, and mild therapeutic hypothermia was able to correct these parameters. Our work thus helps to improve our understanding of the pathophysiology of renal ischemia-reperfusion, and of the assessment and early prediction of its deleterious consequences, as well as our understanding of the protective mechanisms of mild therapeutic hypothermia, which might lead ...