SP473METABOLOMIC APPROACH TO WHITE MATTER LESIONS IN CHRONIC HEMODIALYSIS PATIENTS IDENTIFIES A NOVEL METABOLIC PROFILE ASSOCIATED WITH THESE LESIONS

Abstract

Introduction and Aims: Nearly half of chronic hemodialysis(HD) patients have white matter lesions(WMLs), a form of small-vessel cerebrovascular disease. Whereas advanced age and hypertension are the most accepted risk factors for these lesions, the role of other factors such as plasma lipids is controversial. The aim of this study is to identify a plasmatic metabolic profile associated with these lesions by 1H- Nuclear magnetic resonance(NMR) based-on metabolomics. Methods: A cohort of 63 chronic HD patients without known cerebrovascular disease underwent brain magnetic resonance imaging and were classified into two groups depending on the presence(n=34) or absence(n=29) of WMLs. Plasma samples were collected and analyzed by using 1H NMR. Following spectral preprocessing, the lipoprotein profile was deeply characterized on the whole plasma (Liposcale® test), as well as metabolite profiles of the lipidic and aqueous plasma extractions. Inflammatory (CRPus, IL-6), oxidative stress(glutathione system, glutathione peroxidase) and endothelial function(ADMA) markers were determined. Associations between the metabolomic profile and the presence of WMLs were analyzed by Principal components analyses (PCA) and Partial Least-Squares Discriminant Analysis (PLS-DA). Results: Our results confirm that NMR-based metabolomics can distinguish the biochemical profiles of the CKD patients with and without WMLs . PLS-DA of the NMR and clinical data showed a noticeable separation into the two groups. The classification capability of the cross-validated PLS-DA model remained significant after permutation testing ( p<0.0001). A pro-atherogenic metabolic profile was related to WMLs, presenting an increase of total cholesterol, total triglycerides, LDL and VLDL (cholesterol and triglycerides) and, remarkably, HDL-triglycerides. Alternatively, patients without WMLs presented a protective pattern against developing atherosclerosis characterized by increased HDL-cholesterol levels, LDL-size and levels of eicosapentaenoic and docosahexaenoic fatty acids. The pro-atherogenic pattern was positively associated with the inflammatory and oxidative stress markers, including plasma glutathione, CRPus and IL-6, only in the WMLs group. HDL triglycerides and linoleic acid were significant increased in the WMLs group. Conclusions: Triglycerides-enrichment of HDL and elevated inflammatory parameters, increased in chronic HD patients with WMLs, are known to impair reverse cholesterol transport, and might be linked with small-vessel disease by a diminished cholesterol efflux capacity in the subendothelial space of cerebral microvessels.