Symmetric dimethylarginine is a marker of detrimental outcome in the acute phase after ischaemic stroke: role of renal function

Methylarginines have been shown to interfere with NO (nitric oxide) formation by inhibiting NOS (NO synthase)-ADMA (asymmetric dimethylarginine) and cellular L-arginine uptake into the cell [ADMA and SDMA (symmetric dimethylarginine)]. In a recent study, elevation of SDMA was related to long-term mortality in patients recruited 30 days after a stroke event. In the present study, we aimed at investigating the association of SDMA and adverse clinical outcome in the early phase (first 30 days) after acute ischaemic stroke. A total of 137 patients were recruited immediately upon admission to the emergency unit with an acute ischaemic stroke. Plasma levels of methylarginines were determined by a validated LC-MS/MS (liquid chromatography-tandem MS) method. Patients were prospectively followed for 30 days. A total of 25 patients (18.2%) experienced the primary composite endpoint [death, recurrent stroke, MI (myocardial infarction) and rehospitalization]. SDMA plasma levels were significantly higher in stroke patients compared with patients without event (0.89 ± 0.80 compared with 0.51 ± 0.24 μmol/l; P<0.001). SDMA levels were significantly correlated with markers of renal function. Kaplan-Meier survival analysis demonstrated that cumulative survival decreased significantly with ascending tertiles of SDMA (P<0.001). Our study provides the first data indicating that SDMA is strongly associated with adverse clinical outcome during the first 30 days after ischaemic stroke. Our results strengthen the prognostic value of renal function in patients with stroke and confirm the hypothesis that SDMA is a promising marker for renal function.