Homocysteine and methionine metabolism in renal failure.
Renal insufficiency is invariably accompanied by elevated plasma concentrations of the sulfur-containing and potentially vasculotoxic amino acid homocysteine. There is a strong relationship between glomerular filtration rate and plasma homocysteine concentration. Unlike creatinine, however, homocysteine is avidly reabsorbed in the renal tubules, and its urinary excretion is minimal. There is no evidence that homocysteine is actively removed by the human kidney. In renal insufficiency, plasma concentrations of S-adenosylmethionine, S-adenosylhomocysteine, cystathionine, cysteine, and sulfate are elevated, pointing to a remethylation or distal transsulfuration/oxidation block as the cause of hyperhomocysteinemia in renal failure. Stable isotope techniques have shown that both whole-body homocysteine remethylation and methionine transmethylation are decreased in renal failure, whereas homocysteine transsulfuration seems intact. Metabolic homocysteine clearance (i.e., transsulfuration relative to plasma homocysteine) is decreased to a major extent. These metabolic disturbances in renal failure can only be partially restored with current treatments. Folic acid treatment lowers plasma homocysteine concentration and increases remethylation and transmethylation rates. Plasma homocysteine, however, is not normalized, and metabolic homocysteine clearance by transsulfuration remains impaired. According to the currently available data, effective normalization of plasma homocysteine can only be obtained when its metabolic clearance through transsulfuration is restored.
van Guldener
Coen
C
Department of Internal Medicine, Amphia Hospital, Breda, Maastricht, The Netherlands.
Stehouwer
Coen D A
CD
D015415:Biomarkers / Q000097:blood; D005919:Glomerular Filtration Rate / Q000502:physiology; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D008715:Methionine / Q000097:blood*; D008745:Methylation
D015415:Biomarkers; D006710:Homocysteine; D008715:Methionine