Assessment of Renal Ischemia Reperfusion Induced Injury in Male and Female Rats

Abstract

Acute kidney injury (AKI) is a clinical problem often induced by ischemia reperfusion (IR). Males are reported to have worse outcomes following IR compared to females based on measurements of blood urea nitrogen and creatinine. However, these markers are produced at different levels depending on body mass. The goal of Aims 1 and 2 was to do a complete assessment of the impact of sex on IR to establish a model that displays a sex difference. We measured multiple markers, including inulin clearance which is the gold standard of determining renal function. We determined there is no sex difference in response to IR after 24 hours. However, males had impaired renal function, higher vascular congestion and tubular injury than females 7 days following IR. A consequence of vascular congestion and tubular injury is fluid leakage into interstitial space, which increases renal volume. The goal of Aim 3 was to determine if ultrasound could be used as a tool to detect progressive changes in regional kidney volume following IR. To do this, we compared renal volume measurements with stereological assessment and examined the use of renal volume as an injury marker following IR. We verified the use of ultrasound to monitor renal volume after IR and the changes in volume correlated with the extent of medullary injury. Limiting vascular congestion improves recovery following IR. Pericytes are contractile cells that line the vessels in the renal medulla that are prone to congestion following IR. The goal of Aim 4 was to determine the role of renal pericytes following IR. To do this, we decreased pericytes in rats before IR to determine if this effected injury. We found that lower pericyte density was associated with greater vascular congestion following IR, additionally, males lose more pericytes than females. From these studies, we concluded that there was no sex difference in IR induced injury after 24 hours, however, following 7 days males had poorer recovery than females. We hypothesize that this poorer recovery is attributed to less pericytes in males following IR resulting in the inability to reduce vascular congestion compared to females.