Clinical test of renal guanidinoacetic acid metabolism by oral citrulline and creatine loading

We devised a clinical test of renal metabolism based on the synthesis of guanidinoacetic acid from citrulline in the proximal convoluted tubule. Intravenous administration of a citrulline/creatine solution to rats with modified levels of renal glycine amidinotransferase activity revealed a strong correlation ( r = 0.921) between this activity and urinary guanidinoacetic acid excretion. Citrulline (1.75 g) and creatine (1.50 g) were administered orally to healthy individuals and patients with chronic glomerulonephritis. In the healthy individuals, urinary guanidinoacetic acid excretion increased 5-fold by 2 h after dosing (15.1 ± 2.2 vs. 2.8 ± 1.1 mg/h). In the glomerulonephritis patients, blood clearance of citrulline decreased as the creatinine clearance decreased and urinary guanidinoacetic acid excretion also decreased. Of 56 patients with glomerulonephritis or diabetes mellitus, one had increased urinary guanidinoacetic acid excretion associated with an excess of adrenal androgens. This test appears a useful, noninvasive and simple method for examining the metabolic activity of the renal proximal convoluted tubules.