LAUSR

Red blood cell (RBC) trapping presents as the expansion- and obstruction of-, the outer-medullary capillaries of the kidney with tightly packed RBCs. RBC trapping has been shown to contribute to kidney injury and glomerular filtration rate decline, however, the mechanisms mediating RBC trapping remain unclear. It has previously been proposed that swelling of tubular cells during warm-ischemia initiates RBC trapping by increasing intra-renal pressure. This increase in pressure is thought to compresses the vasa recta capillaries that drain the renal medulla, initiating RBC trapping in the medullary circulation during reperfusion. In the current study we tested the hypothesis that ‘Intra-renal pressure is increased during warm ischemia-reperfusion’. We tested our hypothesis using young male Wistar-Kyoto rats (n=6). We examined pressure changes in the left kidney during ischemia-reperfusion from warm arterial (n=3) and venous (n=3) clamping using micro-serrefines. Rats were anesthetized with isoflurane (2-5%), a midline abdominal incision performed and the left artery and vein isolated. The left kidney was then cleared of connective tissue and placed in a kidney-cup to prevent movement. Intra-renal pressure was measured using a Millar micro-tip catheter pressure transducer which was inserted into the kidney outer-medulla. Intra-renal pressure was recorded during baseline and following 45 minutes of ischemia and 1 hour of reperfusion. Body temperature was maintained throughout the study using a servo-controlled heating table and heat lamp. At the end of the study, the left kidney was harvested and correct catheter placement confirmed. The kidneys were then fixed for later histological analysis. Data were compared using 2-way RM ANOVA (Graphpad Prism).Arterial clamping significantly increased intra-renal pressure (p<0.001). Following arterial clamping, intra-renal pressure rapidly increased reaching a peak of ~30mmHg above baseline after ~6 minutes. Intra-renal pressure then fell slightly averaging 17±3mmHg above baseline over the clamp period. Upon release of the arterial clamp, intrarenal pressure fell to below baseline levels within 270 seconds. Following clamping of the renal vein, intrarenal pressure increased, reaching a peak of 28mmHg above baseline. The increase in average intrarenal pressure across the clamp period was significantly greater with venous compared to arterial clamping (p<0.001), averaging 25±1mmHg. Similar to arterial clamping, intra-renal pressure rapidly fell to baseline levels following removal of the venous clamp.Our data indicate that both arterial and venous clamping increase intra-renal pressure during the clamp/ischemic period. As intra-renal pressure rapidly returns to baseline following removal of the clamp, however, compression of the venous vessels that drain the renal medulla by high intra-renal pressures is unlikely to mediate RBC trapping during reperfusion. NIH NIDDK ISAC 21AU4231, NIH NHLBI P01 HL134604 and an American Heart Association Transformational Project Award 970585 to P.O. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.