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Acute kidney injury (AKI) is a common and serious post-operative complication of cardiac surgery. The value of a predictive biomarker is determined not only by its predictive efficacy, but also by how early this prediction can be made. For a biomarker of cardiac surgery-associated AKI, this is ideally during the intra-operative period. Therefore, in 82 adult patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), we prospectively compared the predictive efficacy of various blood and urinary biomarkers with that of continuous measurement of urinary oxygen tension (UPO2) at pre-determined intra- and post-operative time-points. None of the blood or urine biomarkers we studied showed predictive efficacy for post-operative AKI when measured intra-operatively. When treated as a binary variable (<= or > median for the whole cohort), the earliest excess risk of AKI was predicted by an increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) at 3 h after entry into the intensive care unit (odds ratio [95% confidence limits], 2.86 [1.14-7.21], p = 0.03). Corresponding time-points were 6 h for serum creatinine (3.59 [1.40-9.20], p = 0.008), and 24 h for plasma NGAL (4.54 [1.73-11.90], p = 0.002) and serum cystatin C (6.38 [2.35-17.27], p = 0.001). In contrast, indices of intra-operative urinary hypoxia predicted AKI after weaning from CPB, and in the case of a fall in UPO2 to <=10 mmHg, during the rewarming phase of CPB (3.00 [1.19-7.56], p = 0.02). We conclude that continuous measurement of UPO2 predicts AKI earlier than plasma or urinary NGAL, serum cystatin C, or early post-operative changes in serum creatinine.Copyright © 2021 John Wiley & Sons Australia, Ltd

Introduction: The renal medulla is susceptible to hypoxia during cardiopulmonary bypass (CPB), which may contribute to the development of acute kidney injury. But the speed of onset of renal medullary hypoxia remains unknown. Method(s): We continuously measured renal medullary oxygen tension (MPO2) in 24 sheep, and urinary PO2 (UPO2) as an index of MPO2 in 92 patients, before and after induction of CPB. Result(s): In laterally recumbent sheep with a right thoracotomy (n = 20), even before CPB commenced MPO2 fell from (mean +/- SEM) 52 +/- 4 to 41 +/-5 mmHg simultaneously with reduced arterial pressure (from 108 +/- 5 to 88 +/- 5 mmHg). In dorsally recumbent sheep with a medial sternotomy (n = 4), MPO2 was even more severely reduced (to 12 +/- 12 mmHg) before CPB. In laterally recumbent sheep in which a crystalloid prime was used (n = 7), after commencing CPB, MPO2 fell abruptly to 24 +/-6 mmHg within 20-30 minutes. MPO2 during CPB was not improved by adding donor blood to the prime (n = 13). In patients undergoing cardiac surgery, UPO2 fell by 4 +/- 1 mmHg and mean arterial pressure fell by 7 +/- 1 mmHg during the 30 minutes before CPB. UPO2 then fell by a further 12 +/- 2 mmHg during the first 30 minutes of CPB but remained relatively stable for the remaining 24 minutes of observation. Conclusion(s): Renal medullary hypoxia is an early event during CPB. It starts to develop even before CPB, presumably due to a pressure-dependent decrease in renal blood flow. Medullary hypoxia during CPB appears to be promoted by hypotension and is not ameliorated by increasing blood hemoglobin concentration.Copyright © The Author(s) 2021.

Background: Acute kidney injury (AKI) is common after cardiac surgery requiring cardiopulmonary bypass. Renal hypoxia may precede clinically detectable AKI. We compared the efficacy of two indices of renal hypoxia, (i) intraoperative urinary oxygen tension (UPO2) and (ii) the change in plasma erythropoietin (pEPO) during surgery, in predicting AKI. We also investigated whether the performance of these prognostic markers varies with preoperative patient characteristics. Method(s): In 82 patients undergoing on-pump cardiac surgery, blood samples were taken upon induction of anesthesia and upon entry into the intensive care unit. UPO2 was continuously measured throughout surgery. Result(s): Thirty-two (39%) patients developed postoperative AKI. pEPO increased during surgery, but this increase did not predict AKI, regardless of risk of postoperative mortality assessed by EuroSCORE-II. For patients categorized at higher risk by EuroSCORE-II >1.98 (median score for the cohort), UPO2 <=10 mmHg at any time during surgery predicted a 4.04-fold excess risk of AKI (p =.04). However, UPO2 did not significantly predict AKI in lower-risk patients. UPO2 significantly predicted AKI in patients who were older, had previous myocardial infarction, diabetes, lower preoperative serum creatinine, or shorter bypass times. pEPO and UPO2 were only weakly correlated. Conclusion(s): Intraoperative change in pEPO does not predict AKI. However, UPO2 shows promise, particularly in patients with higher risk of operative mortality. The disparity between these two markers of renal hypoxia may indicate that UPO2 reflects medullary oxygenation whereas pEPO reflects cortical oxygenation.Copyright © 2021 Wiley Periodicals LLC

Computational models have made a major contribution to the field of physiology. As the complexity of our understanding of biological systems expands, the need for computational methods only increases. But collaboration between experimental physiologists and computational modellers (ie theoretical physiologists) is not easy. One of the major challenges is to break down the barriers created by differences in vocabulary and approach between the two disciplines. In this review, we have two major aims. Firstly, we wish to contribute to the effort to break down these barriers and so encourage more interdisciplinary collaboration. So, we begin with a “primer” on the ways in which computational models can help us understand physiology and pathophysiology. Second, we aim to provide an update of recent efforts in one specific area of physiology, renal oxygenation. This work is shedding new light on the causes and consequences of renal hypoxia. But as importantly, computational modelling is providing direction for experimental physiologists working in the field of renal oxygenation by: (a) generating new hypotheses that can be tested in experimental studies, (b) allowing experiments that are technically unfeasible to be simulated in silico, or variables that cannot be measured experimentally to be estimated, and (c) providing a means by which the quality of experimental data can be assessed. Critically, based on our experience, we strongly believe that experimental and theoretical physiology should not be seen as separate exercises. Rather, they should be integrated to permit an iterative process between modelling and experimentation.

Per gram of tissue, the kidneys are among our most highly perfused organs. Yet the renal cortex and, in particular, the renal medulla are susceptible to hypoxia. In turn, hypoxia is a major pathophysiological feature of both acute kidney injury and chronic kidney disease. We identify seven factors that render the kidney susceptible to hypoxia: (1) the large metabolic demand imposed by active reabsorption of sodium; (2) limitations on oxygen delivery to cortical tissue imposed by the density of peritubular capillaries; (3) the poor capacity for angiogenesis in the adult kidney; (4) the limited ability of the renal vasculature to dilate in response to hypoxia; (5) diffusive oxygen shunting between arteries and veins in the cortex and descending and ascending vasa recta in the medulla; (6) the physiological requirement for low medullary blood flow to facilitate urinary concentration; and (7) the topography of vascular‐tubular arrangements in the outer medulla that limit oxygen delivery to the thick ascending limb of Henle's loop. Recent collaborative efforts between anatomists, physiologists, and mathematicians have improved our understanding of the roles of these factors in both physiological regulation of intrarenal oxygenation and development of renal hypoxia under pathophysiological conditions. We are also better able to understand these apparent maladaptations in the context of evolution. That is, they can be explained by the combined effects of historical contingency (our ancestral life in the sea) and selection pressures imposed by the multiple functions of the kidney to regulate extracellular fluid volume, retain water, and control erythrocyte production. Anat Rec, 2019. © 2019 American Association for Anatomy

Introduction: Urinary oxygen tension (PO2) may provide a useful estimate of renal medullary PO2 and thus risk of acute kidney injury (AKI). However, the relationship between urinary PO2 and medullary PO2 could be confounded by variations in urine flow and arterial PO2. In the current study we exploited data we had previously generated, from experimental studies in ovine septic AKI and in patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), to perform a detailed analysis of the influences of urine flow and arterial PO2 on urinary PO2. We also investigated the potential for simultaneous measurement of urine flow and urinary PO2, during CPB, to improve prediction of AKI over that provided by measurement of each variable on its own. Method(s): In ovine septic AKI urine flow, urinary PO2, arterial PO2, and medullary PO2 were measured. In human patients undergoing cardiac surgery requiring CPB urinary PO2 and arterial PO2 were measured continuously and urine flow was estimated every 5 minutes. Result(s): In 28 conscious septic sheep breathing room air, urinary PO2 was more closely correlated with medullary PO2 (r2=0.29) than with arterial PO2 (r2=0.06) or urine flow (r2=0.03). The difference between medullary PO2 and urinary PO2 varied little with urine flow or arterial PO2. In 20 patients, urine flow increased abruptly from 2.81 +/- 0.24 mL/min to 6.53 +/- 0.30 mL/min upon commencement of CPB, usually coincident with a fall in urinary PO2 (Fig. 1). During hyperoxic CPB high values of urinary PO2 were often observed at low urine flow. In 65 patients, low urinary PO2 during CPB (<10 mmHg at any time during CPB) was associated with greater (4.5-fold) risk of AKI. However, the level of urine flow on bypass was not significantly associated with risk of AKI. [Figure presented] Conclusion(s): We developed a method for virtually continuous measurement of urine flow in the operating theatre. We found that urinary PO2 provides a relatively robust estimate of

Introduction: Continuous measurement of bladder urinary oxygen tension (PO2) may provide a real-time surrogate measure of oxygenation in the renal medulla. Therefore, urinary PO2 may be a useful tool for early prediction of acute kidney injury (AKI) and potentially also the management of renal oxygenation in patients with AKI. We examined the relationship between urinary PO2, measured in the intensive care unit (ICU), and development of AKI in patients who had undergone cardiac surgery requiring cardiopulmonary bypass (CPB). Method(s): In 74 patients undergoing on-pump cardiac surgery, bladder urinary PO2 was measured continuously in the ICU using a fibre optic probe placed in the patient's bladder catheter. AKI was diagnosed by modified 'Kidney Disease: Improving Global Outcomes' (KDIGO) criteria, excluding the urine flow criterion. Result(s): Twenty-eight out of 74 patients (37.8%) developed post-operative AKI (18 Stage 1, 7 Stage 2, and 3 Stage 3). The median time to first diagnosis of AKI, using serum creatinine, was 16.9 hours after entry into the ICU (interquartile range (IQR): 13, 32 h). The median duration of monitoring of urinary PO2 was 37.8 hours (IQR: 24.0, 47.3 h). During the first 3 hours after arrival in the ICU, overall mean urinary PO2 (AKI: 19.4 +/- 9.3 vs. non-AKI: 25.3 +/- 9.7 mmHg, p = 0.01), and the nadir (lowest recorded) urinary PO2 (AKI: 12.1 +/- 6.8 vs. non-AKI: 16.0 +/- 5.7 mmHg, p = 0.01) were lower in patients who developed AKI than those who did not. Furthermore, within the first 3 hours of entry to the ICU, 17 of the 28 patients (61%) who developed AKI had urinary PO2 less than or equal to 15 mmHg while this threshold was only reached in 16 of the 46 patients (35%) who did not develop AKI. Patients who developed AKI also experienced longer periods with urinary PO2 less than or equal to 15 mmHg (median time of 10.9 min per hour of measurement) than those who did not (median 0.0 min per hour), p = 0.01. If urinary PO2 fell to 10 mmHg or

Background. Acute kidney injury (AKI) is common after cardiac surgery and profoundly affects postoperative mortality and morbidity. There are no validated methods to assess risk of AKI intraoperatively. Methods. We determined the association between postoperative AKI and intraoperative urinary oxygen tension (PO2), measured via a fiber optic probe in the tip of the urinary catheter, in 65 patients undergoing high-risk cardiac surgery requiring cardiopulmonary bypass (CPB). AKI was diagnosed by modified Kidney Disease: Improving Global Outcomes criteria. Results. Urinary PO2 fell during the operation, often reaching its nadir during rewarming or after weaning from CPB. Nadir urinary PO2 was lower in the 26 patients who developed AKI (mean 6 SD, 8.9 6 5.6 mmHg) than in the 39 patients who did not (14.9 6 10.2 mmHg, P 1/4 0.008). Patients who developed AKI had longer periods of urinary PO2 15 and 10 mmHg than patients who did not. Odds of AKI increased when urinary PO2 fell to 10 mmHg {3.60 [95% confidence interval (CI) 1.27-10.21]} or 5 mmHg [3.60 (95% CI 1.04-12.42), P 1/4 0.04] during the operation. When urinary PO2 fell to 15 mmHg, for more than or equal to the median duration for all patients (4.8 min/h surgery), the odds of AKI were 4.85 (95% CI 1.64-14.40), P 1/4 0.004. The area under the receiver-operator curve for this parameter alone was 0.69, and was 0.89 when other variables with P 0.10 in univariable analysis were included in the model. Conclusion. Low urinary PO2 during adult cardiac surgery requiring CPB predicts AKI, so may identify patients in which intervention to improve renal oxygenation might reduce the risk of AKI.Copyright © The Author(s) 2018.

Aim: Urinary oxygen tension (uPO2) may provide an estimate of renal medullary PO2 (mPO2) and thus risk of acute kidney injury (AKI). We assessed the potential for variations in urine flow and arterial PO2 (aPO2) to confound these estimates. Method(s): In 28 sheep urine flow, uPO2, aPO2 and mPO2 were measured during development of septic AKI. In 65 human patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) uPO2 and aPO2 were measured continuously during CPB, and in a subset of 20 patients, urine flow was estimated every 5 minutes. Result(s): In conscious sheep breathing room air, uPO2 was more closely correlated with mPO2 than with aPO2 or urine flow. The difference between mPO2 and uPO2 varied little with urine flow or aPO2. In patients, urine flow increased abruptly from 3.42 +/- 0.29 mL min-1 to 6.94 +/- 0.26 mL min-1 upon commencement of CPB, usually coincident with reduced uPO2. During hyperoxic CPB high values of uPO2 were often observed at low urine flow. Low urinary PO2 during CPB (<10 mm Hg at any time during CPB) was associated with greater (4.5-fold) risk of AKI. However, low urine flow during CPB was not significantly associated with risk of AKI. Conclusion(s): uPO2 provides a robust estimate of mPO2, but this relationship is confounded by the simultaneous presence of systemic hyperoxia and low urine flow. Urine flow increases and uPO2 decreases during CPB. Thus, CPB is probably the best time to use uPO2 to detect renal medullary hypoxia and risk of post-operative AKI.Copyright © 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

Vascular topology and morphology are critical in the regulation of blood flow and the transport of small solutes, including oxygen, carbon dioxide, nitric oxide, and hydrogen sulfide. Renal vascular morphology is particularly challenging, since many arterial walls are partially wrapped by the walls of veins. In the absence of a precise characterization of three-dimensional branching vascular geometry, accurate computational modeling of the intrarenal transport of small diffusible molecules is impossible. An enormous manual effort was required to achieve a relatively precise characterization of rat renal vascular geometry, highlighting the need for an automated method for analysis of branched vasculature morphology to allow characterization of the renal vascular geometry of other species, including humans. We present a semisupervised method for three-dimensional morphometric analysis of renal vasculature images generated by computed tomography. We derive quantitative vascular attributes important to mass transport between arteries, veins, and the renal tissue and present methods for their computation for a three-dimensional vascular geometry. To validate the algorithm, we compare automated vascular estimates with subjective manual measurements for a portion of rabbit kidney. Although increased image resolution can improve outcomes, our results demonstrate that the method can quantify the morphological characteristics of artery-vein pairs, comparing favorably with manual measurements. Similar to the rat, we show that rabbit artery-vein pairs become less intimate along the course of the renal vasculature, but the total wrapped mass transfer coefficient increases and then decreases. This new method will facilitate new quantitative physiological models describing the transport of small molecules within the kidney.

We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ( ) or microvascular oxygen tension (µPo2) were within ±1 SE of the mean value observed experimentally. The predicted or µPo2 in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted and µPo2. The model parameters analyzed were as follows: 1) the major determinants of renal oxygen delivery ( ) (arterial blood Po2, hemoglobin concentration, and renal blood flow); 2) the major determinants of renal oxygen consumption (V̇o2) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (β)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of and µPo2 to the major the determinants of and V̇o2. The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease.

We assessed the utility of synchrotron-radiation micro-computed tomography (micro-CT) for quantification of the radial geometry of the renal cortical vasculature. The kidneys of nine rats and six rabbits were perfusion fixed and the renal circulation filled with Microfil. In order to assess shrinkage of Microfil, rat kidneys were imaged at the Australian Synchrotron immediately upon tissue preparation and then post fixed in paraformaldehyde and reimaged 24 hours later. The Microfil shrank only 2-5% over the 24 hour period. All subsequent micro-CT imaging was completed within 24 hours of sample preparation. After micro-CT imaging, the kidneys were processed for histological analysis. In both rat and rabbit kidneys, vascular structures identified in histological sections could be identified in two-dimensional (2D) micro-CT images from the original kidney. Vascular morphology was similar in the two sets of images. Radial geometry quantified by manual analysis of 2D images from micro-CT was consistent with corresponding data generated by light microscopy. However, due to limited spatial resolution when imaging a whole organ using contrast-enhanced micro-CT, only arteries ≥100 and ≥60 μm in diameter, for the rat and rabbit respectively, could be assessed. We conclude that it is feasible and valid to use micro-CT to quantify vascular geometry of the renal cortical circulation in both the rat and rabbit. However, a combination of light microscopic and micro-CT approaches are required to evaluate the spatial relationships between intrarenal arteries and veins over an extensive range of vessel size.

To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the eleven branching levels (known as 'Strahler' orders) of the pre-glomerular renal vasculature in the rat, with an analysis of an extensive dataset obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Further, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, peritubular capillaries and veins to tissue. While a number of lines of evidence suggest AV shunting is significant, most importantly our AV oxygen shunting model predicts AV shunting is small under normal physiological conditions (~0.9% of total renal oxygen delivery; range 0.4% to 1.4%), but increases during renal ischemia, glomerular hyperfiltration (~2.1% of total renal oxygen delivery; range 0.84% to 3.36%) and some cardiovascular disease states (~3.0% of total renal oxygen delivery; range 1.2% to 4.8%). Under normal physiological conditions, blood PO2 is predicted to fall by ~16 mmHg from the root of the renal artery to glomerular entry, with AV oxygen shunting contributing ~40% and oxygen diffusion from arteries to tissue contributing ~60% of this decline. Arterial PO2 is predicted to fall most rapidly from Strahler order 4, under normal physiological conditions. We conclude that AV oxygen shunting normally has only a small impact on renal oxygenation, but may exacerbate renal hypoxia during renal ischemia, hyperfiltration and some cardiovascular disease states.

Countercurrent systems have evolved in a variety of biological systems that allow transfer of heat, gases and solutes. For example, in the renal medulla, the countercurrent arrangement of vascular and tubular elements facilitates the trapping of urea and other solutes in the inner medulla, which in turn enables the formation of concentrated urine. Arteries and veins in the cortex are also arranged in a countercurrent fashion, as are descending and ascending vasa recta in the medulla. For countercurrent diffusion to occur, barriers to diffusion must be small. This appears to be characteristic of larger vessels in the renal cortex. There must also be gradients in the concentration of molecules between afferent and efferent vessels, with the transport of molecules possible in either direction. Such gradients exist for oxygen in both the cortex and medulla, but there is little evidence that large gradients exist for other molecules such as carbon dioxide, nitric oxide, superoxide, hydrogen sulfide, and ammonia. There is some experimental evidence for arterial-to-venous (AV) oxygen shunting. Mathematical models also provide evidence for oxygen shunting in both the cortex and medulla. However, the quantitative significance of AV oxygen shunting remains a matter of controversy. Thus, while the countercurrent arrangement of vasa recta in the medulla appears to have evolved as a consequence of the evolution of Henle's loop, the evolutionary significance of the intimate countercurrent arrangement of blood vessels in the renal cortex remains an enigma.

Letter to the editor

Renal arterial-to-venous (AV) oxygen shunting limits oxygen delivery to renal tissue. To better understand how oxygen in arterial blood can bypass renal tissue, we quantified the radial geometry of AV pairs and how it differs according to arterial diameter and anatomic location. We then estimated diffusion of oxygen in the vicinity of arteries of typical geometry using a computational model. The kidneys of six rats were perfusion fixed, and the vasculature was filled with silicone rubber (Microfil). A single section was chosen from each kidney, and all arteries (n = 1,628) were identified. Intrarenal arteries were largely divisible into two "types," characterized by the presence or absence of a close physical relationship with a paired vein. Arteries with a close physical relationship with a paired vein were more likely to have a larger rather than smaller diameter, and more likely to be in the inner-cortex than the mid- or outer cortex. Computational simulations indicated that direct diffusion of oxygen from an artery to a paired vein can only occur when the two vessels have a close physical relationship. However, even in the absence of this close relationship oxygen can diffuse from an artery to periarteriolar capillaries and venules. Thus AV oxygen shunting in the proximal preglomerular circulation is dominated by direct diffusion of oxygen to a paired vein. In the distal preglomerular circulation, it may be sustained by diffusion of oxygen from arteries to capillaries and venules close to the artery wall, which is subsequently transported to renal veins by convection.

Background: Diffusion of oxygen from arteries to veins in the kidney (AV oxygen shunting) acts to limit oxygen delivery to renal tissue. We recently employed computational modeling to identify two factors critical to determination of the quantity of AV oxygen shunting within the renal circulation. These were (i) the distance between the artery and the vein, and (ii) the degree to which the vein wraps around the wall of the artery. Aim: To quantify how the factors in (i) and (ii) above change along the course of the renal circulation. Methods: The renal vasculature of Sprague Dawley rats (n=6) was perfusion fixed and filled with Microfil®. A section from each kidney was chosen and the shortest arterial/arteriolar diameter, distance to the nearest vein, and the degree to which a vein wraps an artery were measured. Results: The diffusion distance between arteries and veins increased with decreasing arte-rial diameter (Figure 1). The proportion of the arterial wall surrounded by the vein (wrapping) decreased as arterial diameter decreased (Figure 2). Conclusions: The spatial relationships (separation and wrapping) between arteries and veins that promote AV oxygen shunting are more prominent in the larger vessels than the smaller vessels of the kidney. These observations challenge the conventional notion that most AV oxygen shunting occurs in the smaller cortical vessels (e.g., interlobular arteries) after the divergence of the cortical and medullary circulations. Thus, AV oxygen shunting may limit oxygen delivery to the renal medulla as well as the renal cortex.

To understand how geometric factors affect arterial-to-venous (AV) oxygen shunting, a mathematical model of diffusive oxygen transport in the renal cortex was developed. Preglomerular vascular geometry was investigated using light microscopy (providing vein shape, AV separation, and capillary density near arteries) and published micro-computed tomography (CT) data (providing vessel size and AV separation; Nordsletten DA, Blackett S, Bentley MD, Ritman EL, Smith NP. IUPS Physiome Project. http://www.physiome.org.nz/publications/nordsletten_blackett_ritman_bentley_smith_2005/folder_contents). A "U-shaped" relationship was observed between the arterial radius and the distance between the arterial and venous lumens. Veins were found to partially wrap around the artery more consistently for larger rather than smaller arteries. Intrarenal arteries were surrounded by an area of fibrous tissue, lacking capillaries, the thickness of which increased from ∼5 μm for the smallest arteries (<16-μm diameter) to ∼20 μm for the largest arteries (>200-μm diameter). Capillary density was greater near smaller arteries than larger arteries. No capillaries were observed between wrapped AV vessel pairs. The computational model comprised a single AV pair in cross section. Geometric parameters critical in renal oxygen transport were altered according to variations observed by CT and light microscopy. Lumen separation and wrapping of the vein around the artery were found to be the critical geometric factors determining the amount of oxygen shunted between AV pairs. AV oxygen shunting increases both as lumen separation decreases and as the degree of wrapping increases. The model also predicts that capillaries not only deliver oxygen, but can also remove oxygen from the cortical parenchyma close to an AV pair. Thus the presence of oxygen sinks (capillaries or tubules) near arteries would reduce the effectiveness of AV oxygen shunting. Collectively, these data suggest that AV oxygen shunting wo