Contribution of hemodilution to renal hypoxia following cardiopulmonary bypass surgery (890.12)

Acute kidney injury (AKI) is a prevalent complication of surgical procedures that require cardiopulmonary bypass (CPB). We have used a mathematical model of the rat kidney to simulate renal hemodynamics during CPB and to study the pathways that can lead to AKI. The model represents vascular blood flow, glomerular filtration, and metabolically driven salt reabsorption along the nephron. Autoregulation is provided by active afferent arteriole constriction initiated by the myogenic response and tubuloglomerular feedback. The model simulates the effects of (i) reduced renal perfusion pressure, which reduces blood flow and glomerular filtration rate (GFR); (ii) hemodilution, which increases GFR; and (iii) hypothermia, which reduces sodium reabsorption and oxygen consumption. Medullary oxygenation is determined by the balance between oxygen consumption, which is increased by hemodilution but decreased due to low perfusion pressure and temperature, and medullary blood supply, which is reduced by hemodilution and the low perfusion pressure. Model simulations suggest that the rise in body temperature following the surgery increases medullary oxygen consumption and drives the kidney into a hypoxic state which may result in AKI. This research was supported in part by NIH grant DK-89066

Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2 Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2 Both intravenous infusion of [Phe(2),Ile(3),Orn(8)]-vasopressin and infusion of N(G)-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8-17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r(2) = 0.87-0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2 Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1-0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10-50% of the change in pelvic urine/medullary Po2 Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury