An update on arginine in sickle cell disease.

INTRODUCTION: Recent knowledge on the pathophysiology of sickle cell disease (SCD) have emphasized the role of hemolysis and nitric oxide (NO) depletion on the occurrence of acute and chronic complications. This new paradigm raises the possibility of innovative therapeutic approaches, including arginine supplementation. Areas covered: This review comments on the role of NO in the regulation of vascular tone, as well as its impaired metabolism in hemolytic diseases. Disturbances in these processes in SCD were detailed considering the functions of endothelial nitric oxide synthase (eNOS), arginase and asymmetric dimethylarginine (ADMA). Therapeutic approaches involving these pathways were discussed with emphasis on the effects of arginine therapy on the normalization of NO levels and its consequent clinical effects, mainly the decrease in the intensity of vaso-occlusive crises. Expert opinion: Considering the complex pathogenesis of the disease and the restricted access to curative therapies, the management of SCD must rely on a combination of therapies covering multiple pathways. Arginine supplementation, a low-cost approach, has shown promising results, which is particulary important considering most of the affected patients still live in unfavorable socioeconomic conditions. These findings should encourage further clinical trials, evaluating other outcomes and specific subpopulations, such as adult patients and compound heterozygotes.