Blood levels of branched-chain α-keto acids in uremia: Therapeutic implications

Summary Serum levels of branched-chain keto acids (BCKA's), i.e., -keto-isocaproic acid (KICA), -keto-isovaleric acid (KIVA) and -keto--methyl-n-valeric acid (KMVA) as well as their corresponding amino acids were determined in uremic patients with compensated chronic renal failure, patients on hemodialysis, and in subjects without renal insufficiency.Uremic patients had significantly lower BCKA levels than controls without renal insufficiency. There was a negative correlation between serum BCKA's and the levels of blood urea and creatinine. BCKA's were detectable in the hemofiltrate. The concentrations of KICA and KMVA were significantly higher, that of KIVA identical compared to the respective concentrations in the hemofiltrate. This suggests a different protein binding of BCKA's. Oral administration of 5 g Ca-KICA to a healthy subject resulted in a transient increase in serum KICA and leucine. The maximum increase in KICA preceded the leucine peak.Serum BCKA levels did not change significantly in patients with compensated renal failure, who were — for 28 days each — first on an unrestricted diet plus supplementation, then solely on an unrestricted diet, followed by a protein-restricted diet (0.5 g/kg/day) plus supplementation and finally on a protein-restricted diet alone. Supplementation was with 5 essential amino acids, 4 keto acids and 1 hydroxyacid (6–9 g/day).The determination of BCKA's in serum offers a promising investigatory tool to study nitrogen metabolism in healthy and uremic subjects and might help to further evaluate the role of keto acids in the treatment of chronic renal failure.