The degree of aortic occlusion in the setting of trauma alters the extent of acute kidney injury associated with mitochondrial preservation

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control noncompressible hemorrhage not addressed with traditional tourniquets. However, REBOA is associated with acute kidney injury (AKI) and subsequent mortality in severely injured trauma patients. Here, we investigated how the degree of aortic occlusion altered the extent of AKI in a porcine model. Female Yorkshire-cross swine (n = 16, 68.1 +/- 0.7 kg) were anesthetized and had carotid and bilateral femoral arteries accessed for REBOA insertion and distal and proximal blood pressure monitoring. Through a laparotomy, a 6-cm liver laceration was performed and balloon inflation was performed in zone 1 of the aorta for 90 min, during which animals were randomized to target distal mean arterial pressures of 25 or 45 mmHg via balloon volume adjustment. Blood draws were taken at baseline, end of occlusion, and time of death, at which point renal tissues were harvested 6 h after balloon deflation for histological and molecular analyses. Renal blood flow was lower in the 25-mmHg group (48.5 +/- 18.3 mL/min) than in the 45-mmHg group (177.9 +/- 27.2 mL/min) during the occlusion phase, which recovered and was not different after balloon deflation. AKI was more severe in the 25-mmHg group, as evidenced by circulating creatinine, blood urea nitrogen, and urinary neutrophil gelatinase-associated lipocalin. The 25-mmHg group had increased tubular necrosis, lower renal citrate synthase activity, increased tissue and circulating syndecan-1, and elevated systemic inflammatory cytokines. The extent of renal ischemia-induced AKI is associated with the magnitude of mitochondrial biomass and systemic inflammation, highlighting potential mechanistic targets to combine with partial REBOA strategies to prevent AKI. NEW & NOTEWORTHY Large animal models of ischemia-reperfusion acute kidney injury (IR-AKI) are lacking. This report establishes a titratable IR-AKI model in swine in which a balloon catheter can be used to alter distal pressures experienced by the kidney, thus controlling renal blood flow. Lower blood flow results in greater renal dysfunction and structural damage, as well as lower mitochondrial biomass, elevated systemic inflammation, and vascular dysfunction.