From rats to man: a perspective on dietary L-arginine supplementation in human renal disease.

Experimental studies have shown both therapeutic and detrimental consequences of modifying dietary L-arginine intake in renal diseases which likely reflect the complexity of L-arginine metabolism. L-Arginine intake is semi-essential and provides substrate for a number of L-arginine metabolites involved in renal pathology. Dietary L-arginine restriction has been identified as a key mediator of the beneficial effects of low protein diets on human renal fibrosis. Supplementing dietary L-arginine in renal diseases with increased iNOS expression appears to be detrimental and thus, may be harmful in immune-mediated human kidney disorders. Increasing L-arginine intake is beneficial in experimental models of hypertensive renal disease. Based upon available data, we believe additional questions must be answered experimentally, not only to prevent an adverse outcome in humans, but to enhance our chances of human trials which will result in substantially better amelioration of disease than currently available.