RENAL UPTAKE AND EXCRETION OF HOMOCYSTEINE IN RATS WITH ACUTE HYPERHOMOCYSTEINEMIA

Background Elevated plasma total homocysteine, an independent risk fac tor for cardiovascular disease, is commonly observed in renal patients . We have previously shown that the kidney is a major site for the rem oval of plasma homocysteine in the rat. The present investigation was performed to further characterize the capacity of the kidney to handle acute elevations in plasma homocysteine concentrations. Methods. Acut e hyperhomocysteinemic conditions (4- to 7-fold > controls) in rats we re produced by either a primed-continuous infusion of L-homocysteine o r exposure to 80:20% nitrous oxide:oxygen, which results in the inhibi tion of methionine synthase. Results. At physiological homocysteine co ncentrations, approximately 15% of the arterial plasma homocysteine wa s removed on passage through the kidney. Renal homocysteine uptake was approximately 85% of the filtered load. The urinary excretion of homo cysteine was negligible (<2%). During acute hyperhomocysteinemia produ ced by the infusion of L-homocysteine, renal homocysteine uptake was i ncreased fourfold and was equivalent to 50% of the infused dose, while urinary excretion remained negligible. Renal homocysteine uptake duri ng nitrous oxide-induced hyperhomocysteinemia increased threefold, wit h urinary excretion remaining negligible. Conclusions. These results p rovide strong evidence that the kidney has a significant capacity for metabolizing acute elevations in plasma homocysteine, and support a ve ry limited role for the re-methylation pathway in renal homocysteine m etabolism.