MO668: An Increase of Free Fatty Acids on Patients Starting Peritoneal Dialysis Suggests an Increased Cardiovascular Risk Beyond Classical Dyslipidemia Biomarkers

Abstract

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and these associated lipid disorders, in turn, contribute to the progression of CKD and its cardiovascular complications. Patients on peritoneal dialysis have a more atherogenic lipid profile than non-dialysis-dependent CKD patients or on HD. In the general population, the reduction of total cholesterol and LDL levels is associated with improved clinical outcomes in terms of morbidity and mortality; however, several studies have failed to obtain these same results in patients on dialysis. The use of lipidomics to detect a broader panel of lipid species can improve the prediction of the different alterations that influence cardiovascular mortality. METHOD This is a single-center prospective observational study of a cohort of CKD patients who start renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD). Data from 39 patients were examined. All samples for routine laboratories and lipidomics studies were obtained the day before starting CAPD (T0) and 6 months after (T1). Samples were analysed on an Ultra-Performance Liquid Chromatography system. The differences in the lipid profile analytical variables between baseline and 6 months after the start of CAPD were analysed. For the lipidomic analysis, each compound was grouped with its possible adducts and compound class based on the International Lipid Classification. RESULTS Thirty-nine patients were enrolled the study. Their mean age was 57.9 ± 16.3 years. The underlying renal diseases were glomerular disease (15 patients), diabetic kidney disease (10), congenital kidney disease (4), hypertensive kidney disease (2), interstitial nephropathy (2) and others (6). Hypertension was present in 96.3% of the patients, diabetes mellitus in 30.8% and 30 of the 39 patients had dyslipidemia (76.9%). Of the group of patients with dyslipidemia, only one of them was not on statin treatment. Table 1 shows the results of the analytical variables of lipid profile, serum glucose and renal function before and 6 months after initiating CAPD. The levels of CT and LDL were lower 6 months after CAPD initiation, but these were not statistically significant. Using the plasma lipid profile, with a mass spectrometry approach, a significant increase (P < 0.05) in total free fatty acids (FFA) was observed from T0 to T1. FFA (16:1) and FFA (18:0) were the FFAs with the highest peak response (Fig. 1). CONCLUSION Our LC-QTOF/MS-based lipidomics approach to study the effect of starting renal replacement therapy with CAPD in patients with CKD shows that total FFAs increased after 6 months on this technique. Within this group of lipids, FA 16:1 (palmitoleic acid) and FA 18:0 (stearic acid) were the ones that increased the most. An earlier study demonstrated that FFA levels are increased in the plasma of CKD patients; moreover, they have reported that higher levels of saturated fatty acids in serum correlate with sudden cardiac death in patients starting HD. Likewise, monounsaturated fatty acids are the products of stearoyl-CoA desaturase (SCD) catalyzed reactions and act as substrates to synthesize phospholipids and triglycerides. The activity of SCD is very high in patients with cardiovascular disease, hypertension and diabetes.