STUDY ON IMPAIRED METABOLISM OF GUANIDINOACETIC ACID IN CHRONIC-RENAL-FAILURE RABBITS WITH SPECIAL REFERENCE TO IMPAIRED CONVERSION OF ARGININE TO GUANIDINOACETIC ACID

Most chronic renal failure (CRF) patients show low serum concentrations of guanidinoacetic acid (GAA). In this study, the author investigated the impaired metabolism of GAA in CRF focusing on the transformation of arginine (Arg) to GAA by analyzing CRF rabbits using C-14-Arg. The CRF group which consisted of 6 CRF rabbits, was compared with 6 normal rabbits (normal group). Blood samples were obtained from each abdominal aorta after a bolus injection of 30 muCi of C-14-Arg into an ear vein of each rabbit. After the last sampling, the left kidney was obtained for measurement of renal glycine amidinotransferase (GAT) activity. In each blood sample, the concentrations of blood urea nitrogen (BUN), serum creatinine (Cr), GAA and Arg were measured. The radioactivity of serum C-14-GAA was measured with a liquid scintillation system. DELTAC-14-GAA was calculated as the difference between the C-14-GAA count and the C-14-background count. Serum concentrations of GAA and renal GAT activity were significantly lower in the CRF group as compared with the normal group. Significant negative correlations were found between the two groups for the following comparisons: serum concentrations of Cr and GAA, concentrations of BUN and renal GAT activity, and serum concentrations of Cr and renal GAT activity. There was a significant positive correlation in the two groups, between renal GAT activity and serum concentrations of GAA. The fact that the concentrations of neither GAA nor Arg changed significantly after the injection of C-14-Arg in either group suggested that the dosage of injected Arg is not sufficient to affect the transformation of Arg to GAA. After 5 min and at the following 5-min intervals, DELTAC-14-GAA was significantly lower in the CRF group than in the normal group. There was a positive correlation between DELTAC-14-GAA after 5 min and renal GAT activity. These results clearly show that renal GAT activity decreases with the progression of renal dysfunction, which directly causes a reduced transformation of Arg to GAA in the kidney, resulting in lower serum concentrations of GAA.