title: A computational model for simulating solute transport and oxygen consumption along the nephrons.
abstract: The goal of this study was to investigate water and solute transport, with a focus on sodium transport (TNa) and metabolism along individual nephron segments under differing physiological and pathophysiological conditions. To accomplish this goal, we developed a computational model of solute transport and oxygen consumption (QO2) along different nephron populations of a rat kidney. The model represents detailed epithelial and paracellular transport processes along both the superficial and juxtamedullary nephrons, with the loop of Henle of each model nephron extending to differing depths of the inner medulla. We used the model to assess how changes in TNamay alter QO2in different nephron segments and how shifting the TNasites alters overall kidney QO2Under baseline conditions, the model predicted a whole kidney TNa/QO2, which denotes the number of moles of Na+reabsorbed per moles of O2consumed, of ∼15, with TNaefficiency predicted to be significantly greater in cortical nephron segments than in medullary segments. The TNa/QO2ratio was generally similar among the superficial and juxtamedullary nephron segments, except for the proximal tubule, where TNa/QO2was ∼20% higher in superficial nephrons, due to the larger luminal flow along the juxtamedullary proximal tubules and the resulting higher, flow-induced transcellular transport. Moreover, the model predicted that an increase in single-nephron glomerular filtration rate does not significantly affect TNa/QO2in the proximal tubules but generally increases TNa/QO2along downstream segments. The latter result can be attributed to the generally higher luminal [Na+], which raises paracellular TNaConsequently, vulnerable medullary segments, such as the S3 segment and medullary thick ascending limb, may be relatively protected from flow-induced increases in QO2under pathophysiological conditions.
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina; alayton@math.duke.edu.
authors.forename: Anita T
authors.initials: AT
authors.lastname: Layton
authors.affiliation: Departments of Medicine and Pharmacology, University of California San Diego, La Jolla, California, and San Diego Veterans Affairs Healthcare System, San Diego, California.
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Université Paris Descartes, Sorbonne Paris Cité, INSERM UMRS 1138, CNRS ERL 8228, Centre de Recherche des Cordeliers, Paris, France; and.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Edwards
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D003198:Computer Simulation; D007668:Kidney / Q000502:physiology*; D008954:Models, Biological; D009399:Nephrons / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats
keywords: epithelial transport; metabolism; oxygen consumption; sodium transport