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 m ass, the actual relationship between protein- or amino acid-induced changes in renal function and urinary albumin excretion (UAE) Is largely unknown i n subjects without renal disease. In humans, infusions of L-arginine have b een used recently in vascular and renal pathophysiological studies. The pre sent study was undertaken to analyze the mechanisms Involved in a particula r effect; namely, the behavior of UAE during amino acid loading. A prospect ive interventional protocol was performed on 10 healthy adults by means of an intravenous infusion of L-arginine. The main results show that L-arginin e 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 simultan eous to an increase in glomerular filtration rate (GFR) and renal plasma fl ow (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)-m icroglobulin (r = 0.05; P = not significant). Furthermore, marked differenc es (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 chang es were found in vehicle-infused individuals. In conclusion, the present st udy shows, in controlled conditions, that I-arginine infusion induces a rel evant Increase in UAE in healthy individuals that significantly exceeds tha t expected from the increase in GFR alone. The intense and simultaneous inc rement in beta(2)-microglobulin excretion strongly suggests that the effect of L-arginine on UAE is, in a relevant part, mediated through a blockade i n the tubular protein reabsorption pathways. However, the profound differen ces observed in the changes induced by L-arginine on UAE and beta(2)-microg lobulin excretion and the differences in the correlation of UAE and beta(2) -microglobulin with respect to GFR suggest that substantial diversity exist s in the mechanisms by which L-arginine affects the renal management of alb umin and beta(2)-microglobulin. These findings are relevant for understandi ng the renal response to L-arginine and protein/amino acid loads. (C) 1999 by the National Kidney Foundation, Inc.