The relationships among renal substrate uptake, the metabolic fates of substrates and renal function in both the dog and rat kidney in vivo and in the isolated perfused rat kidney are being studied. Since more substrate is taken up by kidney than can be oxidized (the "excess renal substrate uptake"), we are attempting to determine whether only certain of the substrates taken up are oxidized to provide energy for renal work functions, particularly Na ion reabsorption. In addition, the functional significance of the non-oxidative fates of the excess renal substrate uptake and renal function is being probed: i.e., are the "excess" substrates utilized to: a) produce new substrates which are more readily stored or utilized by other tissues, so that the kidney serves as a substrate-inter-converter to support function of other tissues? (e.g., fructose or glycerol yields glucose) or b) to produce constituents which are required for the intrarenal synthesis of cell structure which are, in turn, essential for the maintenance of renal function (e.g., tubular cell membrane permeability, maintenance of glomerular basement membrane and podocyte integrity, etc.). Quantification of changes in function would permit a more accurate estimate of the energy requirements for each renal function. The hypothesis that the products formed by the renal substrate interconversion pathways can be regulated by ECF-ph is also being tested. Evidence has now been obtained that lactate and glucose, two substrates utilized by the kidney, each support different renal functions. BIBLIOGRAPHIC REFERENCES: Cohen, J.J. and J.R. Little. Lactate metabolism in the isolated perfused rat kidney: relations to renal function and gluconeogenesis. J. Physiol. 255: 399-414, 1976. Cohen, J.J. and D.E. Kamm. "Renal metabolism: Relation to renal function". Invited Chapter for the 2-volume text "The Kidney" (B.M.Brenner and F.C. Rector, Jr., Eds.), W.B. Saunders & Company, Philadephia, Pa. 1976, pp.126-214.