Branched-chain amino acid metabolism in chronic renal failure

Interorgan exchange of branched-chain amino acids (BCAA) in the postabsorptive state was evaluated in 16 patients with chronic renal failure (CRF) and in 20 subjects with normal renal function, by measuring arterial-venous differences of BCAAs across the leg, brain, hepato-splanchnic (HS) bed, and kidney. In CRF, arterial blood levels of valine are significantly reduced, whereas leucine and isoleucine levels are not different from controls; valine and leucine levels are directly related to GFR. In CRF, a significant decrease in the release of valine by the leg is observed; the leucine release tends to be lower; for both these amino acids, leg release is directly related to their arterial levels. Both ratios of valine and leucine release to total amino acid release by the leg are significantly reduced in CRF. Furthermore, in CRF cerebral uptake and fractional extraction of valine and isoleucine are decreased. In normal subjects, valine and leucine are significantly extracted by the HS bed, whereas in CRF the HS uptake of valine and its fractional extraction fall significantly and leucine uptake is unchanged. The kidney releases significant amounts of leucine both in CRF and in controls. In conclusion, in CRF in the postabsorptive state the exchange of BCAAs, mainly valine, is altered rather early at the major sites of production and utilization, and the flux of these amino acids among the organs is decreased. The primary defect is the decreased output by peripheral tissue, which reduces the supply of BCAAs to the brain and HS bed. Regional metabolic disturbances further impair BCAA utilization.