Baseline Oxysterols and Other Markers of Oxidative Stress, Inflammation and Malnutrition in the Vitamin E and Intima Media Thickness Progression in End-Stage Renal Disease (VIPER) Cohort

Abstract

Background and Objectives: Oxysterols are markers of oxidative stress, levels of which have not yet been reported in hemodialysis (HD) patients. This study was designed to compare levels of the oxysterols 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOH) between a cohort of HD patients and healthy controls. Methods: This nested cross-sectional study reflects baseline (pre-intervention) values for markers of oxidative stress, inflammation and nutrition status in the 160-member vitamin E and carotid intima media thickness progression in end-stage renal disease (VIPER) cohort (age 64.1 ± 8.8, 33.5% female). Age- and sex-matched healthy volunteers served as controls. Plasma oxysterols 7KC and 7βOH were determined by isotope dilution gas chromatography/mass spectrometry. Results: Despite higher plasma α-tocopherol levels in HD patients than controls (36.0 ± 9.3 vs. 31.8 ± 8.4 µmol/l, p = 0.007), 7KC levels (9.8 ± 6.9 vs. 5.9 ± 2.8 nmol/mmol cholesterol, p < 0.0001) and 7βOH levels (8.7 ± 4.3 vs. 2.7 ± 1.6 nmol/mmol cholesterol, p < 0.0001) were higher in HD patients. The oxysterol 7βOH was significantly, inversely associated with prealbumin (r = –0.18, p = 0.03), though neither oxysterol was significantly associated with any other marker of oxidative stress, inflammation or nutrition status and did not discriminate for CVD in HD patients. Conclusions: Elevated levels of the oxysterols 7KC and 7βOH indicate that HD patients are in a state of oxidative stress compared to healthy controls. However, oxysterols 7KC and 7βOH did not appear to contribute additional information about oxidative stress among HD patients.

Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins

“…In healthy subjects, oxysterols are found at very low plasma concentrations [210] (Table 1). These concentrations are significantly increased in CKD patients compared to a control population and especially in end-stage renal disease (ESRD) patients undergoing hemodialysis [113,114]. Moreover, Siems et al reported an increase of their concentration after an HD session [114].…”

Oxysterol as a Marker of Atherogenic Dyslipidemia in Adolescence

“…Oxysterols are the derivatives of enzymatic or nonenzymatic cholesterol oxidation, and they may be involved in the initiation and progression of atherosclerosis (7). Many studies have reported the presence of different types of predominantly free radical-induced oxysterols in human lipoproteins, femoral plaques, and atherosclerotic aorta (4,8,9). Conversely, enzymatically generated oxysterols are indicated to play a role in the regulation of cholesterol metabolism (10) and act as important modulators of insulin by acting as agonists of liver X receptors (LXRs) (10).…”

Wishful Thinking: The Surprisingly Sparse Evidence for a Relationship between Oxidative Stress and Cardiovascular Disease in Hemodialysis Patients

“…Only seven cross-sectional studies have investigated the possible association between biomarkers of oxidative stress and thickness of the intima-media of the carotid artery. The association was demonstrated in three studies (34)(35)(36), but not in another three (37)(38)(39). In the study by Dursun et al (40), some oxidative stress biomarkers were associated with carotid artery intima-media thickness ( Table 2).…”

“…Only seven cross‐sectional studies have investigated the possible association between biomarkers of oxidative stress and thickness of the intima‐media of the carotid artery. The association was demonstrated in three studies , but not in another three . In the study by Dursun et al.…”