PHYSICO-CHEMICAL ASPECTS OF RENAL TRANSPORT PROCESSES

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The proposed research is aimed at the development of accurate and predictive theories for two elements of renal function. The first of these concerns the mechanisms whereby glomerular capillaries selectively restrict the filtration of certain macromolecules. Proteinuria resulting from a disruption of this filtration barrier is a hallmark of kidney disease, and a better understanding of normal and altered glomerular selectivity promises to provide insight into the underlying disease mechanisms, as well as to offer new methods for monitoring the progress of patients. Theoretical models will be developed or extended to describe movement of macromolecules of varying size, charge and molecular configuration through porous membranes. The membranes will be represented either as an array or cylindrical pores or as a network of fibers. In vitro experiments will be used to examine elements of these theories and to characterize test macromolecules. The theories will be used to interpret measurements of glomerular selectivity in studies of experimental renal disease in rats, and in various human glomerulopathies. Adjustments in the rate at which filtered bicarbonate is reabsorbed by the kidney provide one of the body's major defenses against disruptions of acid-base balance. Recent measurements of carbon dioxide partial pressure (PCO2) in the rat kidney have raised a number of important questions concerning the intrarenal handling of carbon dioxide and bicarbonate, which provide a second focus for the proposed research. Theoretical models will be developed to rationalize observed differences in PCO2 between peritubular capillary and arterial blood, and among tubules and microvessels on the surface of the renal cortex. These models will involve detailed consideration of mass transfer, chemical kinetics, and chemical equilibria in blood vessels and renal tubules. Comparison of the theoretical predictions with experimental results in the rat should provide a sensitive test of current hypotheses concerning bicarbonate reabsorption. The proposed research will involve collaboration among chemical engineers, renal physiologists and clinical nephrologists.