Accounting for oxygen in the renal cortex: A computational study of factors that predispose the cortex to hypoxia

Chang Joon Lee, Bruce S Gardiner, Jennifer P. Ngo, Saptarshi Kar, Roger G. Evans, David W. Smith

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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 (PtO2) or microvascular oxygen tension (μPO2) were within ±1 SE of the mean value observed experimentally. The predicted PtO2 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 PtO2 and μPO2. The model parameters analyzed were as follows: 1) the major determinants of renal oxygen delivery (ḊO2) (arterial blood PO2, hemoglobin concentration, and renal blood flow); 2) the major determinants of renal oxygen consumption (VO2) [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 PtO2 and μPO2 to the major the determinants of ḊO2 and VO2. 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.

Original languageEnglish
Pages (from-to)F218-F236
Number of pages19
JournalAmerican Journal of Physiology-Renal Physiology
Volume313
Issue number2
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • Acute kidney injury
  • Capillary rarefaction
  • Chronic kidney disease
  • Hypoxia
  • Oxygen tension
  • Renal cortex
  • Renal oxygenation

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