Blood levels of branched-chain amino acids and α-ketoacids in uremic patients given keto analogues of essential amino acids

Serum levels of the branched-chain ketoacids, α-keto-isocaproic acid, α-keto-isovaleric acid, and α-keto-β-methyl-n-valeric acid, and their corresponding amino acids were determined in uremic patients with compensated chronic renal failure and in subjects without renal insufficiency. Uremic patients had significantly lower branched-chain ketoacid levels than controls. Unlike controls, α-keto-isocaproic acid and α-keto-β-methyl-n-valeric acid levels did not decrease in uremic subjects in response to an oral glucose tolerance test. Serum branched-chain ketoacid levels did not change significantly in uremic patients who were treated for 28 days with 1) an unrestricted diet supplemented with four essential amino acids, tyrosine, four ketoacids, and one hydroxyacid (6 to 9 g/day), 2) an unrestricted diet, 3) a protein-restricted diet (0.5 g/kg per day) supplemented as above, and 4) a protein-restricted diet without supplementation. The oral glucose tolerance test improved in all patients receiving an unrestricted diet with supplementation. The various dietetic regimens had no consistent effects either on the intravenous glucose tolerance test, or on serum levels of insulin and C-peptide. It is concluded that uremic patients with glucose intolerance are also likely to have an abnormal metabolism of amino acids. If normalization of the decreased serum branched-chain amino acid levels in uremia is a valid criterion for successful therapy with keto analogues of essential amino acids, then the dosage used in this study is too low.