Plasma Amino Acid Profile and L-arginine Uptake in Red Blood Cells from Malnourished Uremic Patients

Abstract

Patients with end-stage chronic renal failure (CRF) (uremia) have a high prevalence of inflammation, malnutrition, and oxidative stress. All of these features seem to be associated with the increased cardiovascular mortality observed in these patients. Nitric oxide (NO) is involved in the pathogenesis of CRF. The present study investigates the effects of nutritional status on L-arginine transport (NO precursor), plasma amino acid profile, and concentration of tumor necrosis factor (TNF)-alpha in uremic patients on hemodialysis (HD). A total of 32 uremic patients on regular HD and 16 healthy controls were included in this study. Kinetic studies of L-arginine transport, mediated by cationic transport systems y(+) and y(+)L into red blood cells, plasma concentrations of amino acids (measured by high-performance liquid chromatography), and plasma TNF-alpha level (evaluated by enzyme-linked immunosorbent assay), were analyzed in malnourished and well-nourished patients (isolated by body mass index). L-arginine influx by system y(+) in red blood cells (micromol/L cells(-1)h(-1)) was increased in both malnourished (377 +/- 41) and well-nourished (461 +/- 63) patients with CRF compared with controls (287 +/- 28). Plasma levels of all cationic amino acids (L-arginine, L-ornithine, and L-lysine) were low in uremic patients compared with controls. Among the uremic population, the reduction in plasma cationic amino acids levels was greater in malnourished patients. L-cysteine and L-glutamate, precursors of glutathione, were dramatically increased in plasma from uremic patients, independently of nutritional status. In addition, TNF-alpha concentration in plasma was enhanced in malnourished uremic patients (3.4 +/- 0.7 pg/mL) compared with controls (1.2 +/- 0.1 pg/mL) and well-nourished patients (1.9 +/- 0.1 pg/mL). Our results suggest an increased catabolism of cationic amino acids, inflammatory markers, and oxidative stress in CRF, especially in malnourished patients. The reduced plasma concentration of plasma L-arginine is counterbalanced by enhanced rates of transport, resulting in an activation of NO synthesis in uremia.