Higher levels of SDMA and not ADMA are associated with poorer survival of trial patients with systemic ANCA-associated vasculitis

Abstract

Objective: Endothelial dysfunction, increased cardiovascular events (CVE), and accelerated atherosclero-sis have been described in patients with small vessel vasculitis and collagen vascular disease. Identifyingpredictors of cardiovascular risk will help to optimize short- and long-term care of patients with vasculi-tis. The present study investigates the predictive role of the endogenous nitric oxide synthase (NOS) in-hibitor asymmetric dimethylarginine (ADMA) and its stereoisomer symmetric dimethylarginine (SDMA)for cardiovascular risk, all-cause mortality, and renal function in patients with anti-neutrophil-cytoplas-mic antibodies-associated small vessel vasculitis (AASV) subjected to standardized treatment regimensin four European Vasculitis Study Group trials representing all stages of renal disease.Methods: Sera from 89 patients with AASV were available for measuring SDMA, ADMA, and arginine usingliquid chromatography/mass spectrometry at the time of active disease and remission. Clinical data on dis-ease activity, remission, relapse rate, and 5-year follow-up data for CVE and renal outcome were collected.Results: Symmetric dimethylarginine and ADMA levels were not predictive of CVE at 5 years of follow-up. Theoverall CVE rate was low in the present cohort of AASV (8%). However, SDMA, and not ADMA, levels weresignificantly associated with poorer survival (death/ESRD) independent of entry glomerular filtration rate.Conclusion: This novel outcome in a well-defined group of patients with AASV might indicate a dif-ferent mechanism of endothelial response in AASV as compared with atherosclerosis. This should befurther explored in a larger cohort of AASV patients with a higher CVE rate and/or a longer follow-up.Moreover, these findings should be correlated to other markers of vascular damage.