Uremia, Atherothrombosis and Malnutrition: The Role of L-arginine- Nitric Oxide Pathway

Tatiana   M.C.   Brunini; Clarissa   D.   da Silva; Mariana   A.S.   Siqueira; Monique   B.   Moss; Sergio   F. F.   Santos; Antonio   C.   Mendes-Ribeiro

Abstract

The uraemic syndrome is a complex condition that results from an accumulation of multiple waste compounds, combined with failure of the endocrine and homeostatic functions of the kidney in end-stage chronic renal failure (CRF) patients. Recently it has become clear that uraemia is a microinflammatory condition with a significant increase in inflammation markers. Malnutrition is a common pathological condition which exacerbates cardiovascular mortality in uraemic patients. Inadequate diet and a state of persistent catabolism play major roles in uraemic malnutrition, yet the underlying mechanisms have not been completely clarified. Malnourished patients present elevated levels of circulating cytokines, further aggravating the oxidative and inflammatory characteristics of uraemia. It has been suggested that abnormalities in nitric oxide bioactivity, coupled with malnutrition and inflammation, may contribute to increased incidence of atherothrombotic events in uraemia. Amongst the earliest indications of nutritional deficiency are low concentrations of plasma amino acids, including L-arginine, the precursor for nitric oxide (NO) synthesis. Atherosclerosis is an inflammatory disorder and NO is an important mediator of inflammation. There is a close association between thrombosis and platelet aggregation, and NO is involved in all stages of platelet activation. L-arginine inhibits platelet aggregation both in vitro and in vivo, while L-NMMA (NG-monomethyl-L-arginine), an endogenous L-arginine analogue and inhibitor of NO synthase (NOS), increases platelet activation and adhesion. The majority of studies in animal models and human patients indicate that the systemic production of NO is increased in uraemia. CRF patients show reduced plasma concentration of L-arginine, and the enhancement of L-arginine transport is essential to maintain increased NO synthesis in platelets taken from these patients. The present review provides an overview of recent advances in the understanding of the association among malnutrition, chronic inflammation and the L-arginine-nitric oxide pathway in uraemic patients, and related potential interventions that could improve clinical outcome in chronic renal failure.

Keywords: L-arginine transport, nitric oxide, platelets, uremia, malnutrition, inflammation

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