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

Abstract

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.

Renal oxygenation: From data to insight

“…Using a model of oxygen diffusion across the ureteric urothelium, Sgouralis and colleagues identified urine flow and arterial PO 2 as the major factors confounding the prediction of inner medullary PO 2 from measurement of urinary PO 2 . 33 This has recently been confirmed in experimental and clinical studies. 114 The next challenge in this field will be to scale such models up so they can be used to predict renal medullary PO 2 from urinary PO 2 in humans.…”

“…Following this logic to its conclusion, when confidence in a model has become sufficiently high, following exhaustive model validation, the model can act as a rational basis for developing patient/cohort‐specific treatment strategies or monitoring systems. An example is use of computational models to predict what would happen to oxygenation of the renal medulla during cardiopulmonary bypass, and to predict renal medullary tissue PO 2 from measurement of bladder urine PO 2 . But as described below, computational models are improving our understanding of the physiology of renal oxygenation on multiple fronts.…”

“…There has also recently been renewed interest in the potential for measurement of urinary oxygen tension for assessment of renal medullary oxygenation and risk of AKI . Indeed, experimental observations indicate a close agreement between urinary and medullary PO 2 . But as with any indirect measure, a major challenge is to understand the factors that confound the relationship between the variable of interest (renal medullary PO 2 ) and the indirect measure (bladder urine PO 2 ).…”

“…An example is use of computational models to predict what would happen to oxygenation of the renal medulla during cardiopulmonary bypass, [30][31][32] and to predict renal medullary tissue PO 2 from measurement of bladder urine PO 2 . 31,33 But as described below, computational models are improving our understanding of the physiology of renal oxygenation on multiple fronts.…”

“…118 Indeed, experimental observations indicate a close agreement between urinary and medullary PO 2 . 33,[119][120][121][122] But as with any indirect measure, a major challenge is to understand the factors that confound the relationship between the variable of interest (renal medullary PO 2 ) and the indirect measure (bladder urine PO 2 ). Using a model of oxygen diffusion across the ureteric urothelium, Sgouralis and colleagues identified urine flow and arterial PO 2 as the major factors confounding the prediction of inner medullary PO 2 from measurement of urinary PO 2 .…”