Induction of microalbuminuria by L-arginine infusion in healthy individuals:: An insight into the mechanisms of proteinuria

Despite evidence from individuals with diabetes mellitus or reduced renal mass, the actual relationship between protein- or amino acid-induced changes in renal function and urinary albumin excretion (UAE) Is largely unknown in subjects without renal disease. In humans, infusions of L-arginine have been used recently in vascular and renal pathophysiological studies. The present study was undertaken to analyze the mechanisms Involved in a particular effect; namely, the behavior of UAE during amino acid loading. A prospective interventional protocol was performed on 10 healthy adults by means of an intravenous infusion of L-arginine. The main results show that L-arginine induced a significant increase in UAE from 13.1 +/- 3.8 before to 53.3 +/- 11.1 mu g/min after the infusion (P < 0.005). This increment was simultaneous to an increase in glomerular filtration rate (GFR) and renal plasma flow (RPF). Furthermore, L-arginine markedly increased the urinary excretion of beta(2)-microglobulin. UAE correlated significantly with GFR (r = 0.738; P = 0.014) and RPF (r = 0.942; P < 0.0001), but not with urinary beta(2)-microglobulin (r = 0.05; P = not significant). Furthermore, marked differences (P = 0.001) were found between the percentage of increase in UAE (306.8% +/- 163.2%) with respect to either albumin filtered load (FLAlb; 57.9% +/- 16.3%) and beta(2)-microglobulin excretion (1,088.5% +/- 424.6%). No changes were found in vehicle-infused individuals. In conclusion, the present study shows, in controlled conditions, that I-arginine infusion induces a relevant Increase in UAE in healthy individuals that significantly exceeds that expected from the increase in GFR alone. The intense and simultaneous increment in beta(2)-microglobulin excretion strongly suggests that the effect of L-arginine on UAE is, in a relevant part, mediated through a blockade in the tubular protein reabsorption pathways. However, the profound differences observed in the changes induced by L-arginine on UAE and beta(2)-microglobulin excretion and the differences in the correlation of UAE and beta(2)-microglobulin with respect to GFR suggest that substantial diversity exists in the mechanisms by which L-arginine affects the renal management of albumin and beta(2)-microglobulin. These findings are relevant for understanding the renal response to L-arginine and protein/amino acid loads. (C) 1999 by the National Kidney Foundation, Inc.