Arginine synthesis by the proximal convoluted tubule in rats with chronic renal failure

The high plasma level of citrulline (Cit) is one of a number of abnormalities in the plasma amino acid pattern in chronic renal failure (CRF). Synthesis of arginine (Arg) from citrulline in the kidney is the major source of Arg for the body. In order to evaluate the renal activity of Arg synthesis in CRF, we studied arginine production in proximal convoluted tubules (PCT) isolated from male Sprague-Dawley rats 1 month after 5/6 nephrectomy and from sham-operated rats (n = 6 of each). PCT segments were incubated in a sealed chamber with 50 or 200 microM of [L-ureido 14C]-Cit (simulating in vivo plasma concentrations in healthy rats or rats with CRF, respectively). Arginase and urease were added to the medium to hydrolyze Arg into 14CO2 + NH3. 14CO2 was trapped in KOH and counted. Results showed that: (1) in CRF, Arg production per unit tubular length is increased in proportion to hypertrophy of PCT (x 1.5); (2) in CRF, as in the healthy kidney, Arg production increases with Cit concentration (x 2.5 from Cit 50 to 200 microM). Taking into account the hypertrophy and the elevation in Cit concentration, the increase in Arg production per unit length (x 3.6) is not sufficient to compensate for the reduction in nephron number. Most likely, a greater length of maximal tubule is recruited for renal Arg synthesis in CRF.