Arginine, citrulline, and nitric oxide metabolism in. end-stage renal disease patients

The kidneys are thought to be a major site of net de novo arginine synthesi s, but the quantitative status of arginine metabolism and its substrate pre cursor relationship to nitric oxide (NO) synthesis in end stage renal disea se (ESRD) patients have not been characterized. We have investigated kineti c aspects of whole body arginine metabolism in six patients with ESRD. They received two pre- and two post-hemodialysis intravenous tracer infusion st udies with L-[guanidino-N-15(2)]arginine and L-[C-13]leucine during the fir st study, and L-[5-C-13]arginine and L-[5-C-13-ureido,5,5,H-2(2)]citrulline during the second study. Arginine homeostasis in ESRD patients was found t o be associated with a lower rate ofarginine oxidation, and despite the dec rease in renal function, the rate of de novo arginine synthesis appeared to be preserved. Plasma citrulline concentrations and flux were also elevated in these subjects compared with healthy adults. The rate of whole body NO synthesis was increased in the ESRD patients, but apparently not different pre- and post-hemodialysis therapy. The anatomic site(s) responsible for th e maintenance of net de novo arginine synthesis and for the elevated NO syn thesis and its pathophysiological importance in ESRD remain to be establish ed.