Guanidinosuccinic Acid in Renal Failure, Experimental Azotemia and Inborn Errors of the Urea Cycle

An Improved method of isolation and quantitation, using Dowex-1 ion-exchange chromatography and paper electrophoresis, has permitted efficient recovery of guanidinosuccinic acid from serum, urine and cerebrospinal fluid. Mean concentration of this acid in normal urine is 1.71 ± 1.60 (SD) mg/100 ml, and 5.35 ± 2.68 mg/100 ml in urine from uremic patients. Serum and cerebrospinal-fluid levels are also increased in uremia. In patients undergoing peritoneal dialysis, guanidinosuccinic acid was dialyzable. The metabolic pathway for synthesis of guanidinosuccinic acid is unknown. The increased excretion of this compound in rats treated with arginine, coupled with the failure to demonstrate the metabolite in the urine of patients suspected of having arginine deficiency resulting from genetic defects of the urea cycle, suggests that arginine is an intermediate in guanidinosuccinic acid synthesis.