Dietary L-arginine in renal disease

The amino acid L-arginine is a substrate for at least three products involved extensively in tissue injury and fibrosis. L-arginine is metabolized to L-proline, a major constituent of the collagen that makes up fibrotic extracellular matrix. L-arginine is a precursor for polyamines, which are required for proliferative responses characteristic of many renal disease. L-arginine is also the sole substrate for generation of nitric oxide (NO) which, produced in large quantities by macrophages, has been implicated in tissue injury. On the other hand, NO produced in small quantities by endothelium is a critical vasodilator. Given the importance of elevated intraglomerular pressure in renal injury, it is perhaps not surprising that dietary L-arginine supplementation increase NO generation and is beneficial in reducing intraglomerular pressure and subsequent disease. Other data, based on the therapeutic effects of low protein diets, have suggested that L-arginine restriction limits NO-mediated glomerular injury and greatly reduces matrix accumulation, consistent with the idea that limitation of substrate effectively diminishes injurious NO levels, polyamine synthesis, and collagen production.