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

Abstract 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 μg/min after the infusion ( P 2 -microglobulin. UAE correlated significantly with GFR ( r = 0.738; P = 0.014) and RPF ( r = 0.942; P 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 β 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 l -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 β 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 β 2 -microglobulin excretion and the differences in the correlation of UAE and β 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 β 2 -microglobulin. These findings are relevant for understanding the renal response to l -arginine and protein/amino acid loads.