Authors of a study in this week’s issue of THE LANCET conclude that increased concentrations of the naturally occuring organic compound asymmetrical dimethylarginine (ADMA) is a strong predictor of death and cardiovascular disease in haemodialysis patients. A research letter also published this week suggests that increased concentrations of ADMA may indicate a cardiovascular risk in men with normal kidney function.
The plasma concentration of ADMA, which has been linked to endothelial dysfunction and atherosclerosis in the general population, is raised in patients with end-stage renal disease and could contribute to the high cardiovascular risk in patients with chronic renal failure. Rainer Böger from University Hospital Hamburg-Eppendorf, Germany, and colleagues investigated the relation between cardiovascular risk factors and plasma ADMA concentration in 225 haemodialysis patients, and tested the predictive power of ADMA for death and cardiovascular outcomes.
Patients had standard dialysis three times a week. Cardiovascular events were recorded over an average follow-up of 33 months. ADMA concentration in plasma was directly related to concentrations of fibrinogen and L-arginine in plasma, duration of dialysis treatment, and serum cholesterol concentration. 83 patients died, 53 (64%) from cardiovascular causes. Concentrations of plasma ADMA ranked as the second most important factor (after age) predicting overall death and cardiovascular events.
In a research letter (p 2127), Reijo Laaksonen and colleagues from the University of Helsinki, Finland, report that middle-aged men (with normal kidney function) from eastern Finland who were in the top quartile for ADMA concentration were four times more likely of having acute coronary events than men with lower ADMA concentrations.
In an accompanying Commentary (p 2096), Patrick Vallance from University College London, UK, concludes: “…The finding that ADMA predicts outcome in patients with renal disease may be of direct and practical clinical relevance.” Referring to the Finnish study, he adds: “Since renal function in this group was not impaired and thus, excretion of ADMA presumably was normal, DDAH [the enzyme dimethylarginine dimethylaminohydrolase] dysfunction is strongly implicated as a primary mechanism. It will now be interesting to examine whether ADMA is also a predictor of event rates in other cardiovascular disorders in which it accumulates, and whether DDAH dysfunction produces an adverse metabolic change equivalent to renal failure in individual cells and tissues.”
Contact: Dr Rainer H Böger, Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany; T) +49 40 42 803 97 59; F) +49 40 42 803 97 57; E) boeger@uke.uni-hamburg.de
Dr Reijo Laaksonen, current address: Department of Neurology, Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070 Brussels, Belgium; T) +32 2 555 3992; F) +32 2 555 3942; E) reijo.laaksonen@helsinki.fi
Dr Patrick Vallance, Centre for Clinical Pharmacology and Therapeutics, Department of Medicine, University College London, London WC1E 6JJ, UK; E) rmhapav@ucl.ac.uk
Journal
The Lancet