Clinical Implications of Elevated Asymmetric Dimethylarginine in Chronic Kidney Disease and End-Stage Renal Disease

Establishing solutes that accumulate in body fluids in renal insufficiency as authentic uremic toxins is a process demanding in vitro and in vivo animal experiments as well as observational and interventional studies in humans. Asymmetric dimethylarginine (ADMA) is listed among the few uremic solutes close to the inference criteria for causal involvement into the pathogenesis of the uremic syndrome. In healthy subjects, the intravenous administration of this methylarginine, such as to bring circulating ADMA to supraphysiologic concentration, raises peripheral vascular resistances and arterial pressure. In uremic patients, ADMA is strongly associated with carotid atherosclerosis and with overall and cardiovascular mortality. Yet we still need the decisive proof that this substance is causally involved in the high risk of death and cardiovascular complications of this population-that is, an intervention study proving that reducing ADMA levels translates into better clinical outcomes.