title: Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia.
abstract: 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 ([Formula: see text]) or microvascular oxygen tension (µPo2) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo2in 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 [Formula: see text] and µPo2The model parameters analyzed were as follows:1) the major determinants of renal oxygen delivery ([Formula: see text]) (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 [Formula: see text] and µPo2to the major the determinants of [Formula: see text] and V̇o2The 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.
authors.affiliation: Faculty of Engineering and Mathematical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Chang-Joon
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: School of Engineering and Information Technology, Murdoch University, Perth, Western Australia, Australia; and.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Gardiner
authors.affiliation: Cardiovascular Disease Program, Biosciences Discovery Institute and Department of Physiology, Monash University, Melbourne, Sydney, Australia.
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Ngo
authors.affiliation: Faculty of Engineering and Mathematical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Saptarshi
authors.identifier: http://orcid.org/0000-0002-3788-372X
authors.initials: S
authors.lastname: Kar
authors.affiliation: Cardiovascular Disease Program, Biosciences Discovery Institute and Department of Physiology, Monash University, Melbourne, Sydney, Australia.
authors.forename: Roger G
authors.identifier: http://orcid.org/0000-0002-9241-0757
authors.initials: RG
authors.lastname: Evans
authors.affiliation: Faculty of Engineering and Mathematical Sciences, The University of Western Australia, Perth, Western Australia, Australia; david.smith@uwa.edu.au.
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D015687:Cell Hypoxia; D003198:Computer Simulation; D004195:Disease Models, Animal; D006439:Hemodynamics; D006801:Humans; D007672:Kidney Cortex / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008954:Models, Biological; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D015203:Reproducibility of Results
chemical_list: D010100:Oxygen
keywords: acute kidney injury; capillary rarefaction; chronic kidney disease; hypoxia; oxygen tension; renal cortex; renal oxygenation