A Matched Case-Control Study of Noncholesterol Sterols and Fatty Acids in Chronic Hemodialysis Patients.

Dyslipidemia is common among patients on hemodialysis, but its etiology is not fully understood. Although changes in cholesterol homeostasis and fatty acid metabolism play an important role during dialysis, the interaction of these metabolic pathways has yet to be studied in sufficient detail. In this study, we enrolled 26 patients on maintenance hemodialysis treatment (high-volume hemodiafiltration, HV HDF) without statin therapy (17 men/9 women) and an age/gender-matched group of 26 individuals without signs of nephropathy. The HV-HDF group exhibited more frequent signs of cardiovascular disease, disturbed saccharide metabolism, and altered lipoprotein profiles, manifesting in lower HDL-C, and raised concentrations of IDL-C and apoB-48 (all p < 0.01). HV-HDF patients had higher levels of campesterol (p < 0.01) and ß-sitosterol (p = 0.06), both surrogate markers of cholesterol absorption and unchanged lathosterol concentrations. Fatty acid (FA) profiles were changed mostly in cholesteryl esters, with a higher content of saturated and n-3 polyunsaturated fatty acids (PUFA) in the HV-HDF group. However, n-6 PUFA in cholesteryl esters were less abundant (p < 0.001) in the HV-HDF group. Hemodialysis during end-stage kidney disease induces changes associated with higher absorption of cholesterol and disturbed lipoprotein metabolism. Changes in fatty acid metabolism reflect the combined effect of renal insufficiency and its comorbidities, mostly insulin resistance.

Dyslipidemia in patients with chronic kidney disease: etiology and management.

The worldwide population is burdened with chronic kidney disease (CKD) from 10-13 %. Patients with CKD subsequently die to cardiovascular disease (CVD) and their complications. In the Czech population, in 2016, the number of patients with end stage renal disease (ESRD) on regular dialytic treatment was 6 739, or 674/1 000 000 inhabitants. Overall mortality in regular dialysis treatment patients was 18.4 % in 2016, of which 43 % died of cardiovascular complications. In view of this fact, a number of expert groups are concerned, among other things, with the problems of lipid metabolism disorders, with the aim of finding a common predictive marker (preferably also therapeutically qualifiable) to stratify patients dialyzed or potentially indicating hypolipidemic therapy. The aim of possible interventions is to minimize cardiovascular risk and subsequent complications resulting from cardiovascular disease (CVD), thus improving the quality of life of regular dialysis treatment patients.

Associations of Serum Uric Acid with Endogenous Cholesterol Synthesis Indices in Men with High Cardiometabolic Risk.

Background: Patients with metabolic syndrome (MetS) have increased endogenous synthesis of cholesterol, together with lower level of intestinal cholesterol absorption. However, less is known about how individual metabolic disturbances linked to MetS correlate with dysregulated cholesterol homeostasis. Methods: We consecutively examined 178 probands (91 women/87 men) characterized by the presence of one or two components of MetS (group with an increased cardiometabolic risk [CMR]) and 42 healthy controls (24 men/18 women) of similar age, as well. In all probands, the surrogate markers for cholesterol biosynthesis (lathosterol) and absorption (campesterol and ß-sitosterol) were measured by capillary gas chromatography. In CMR group, we performed multivariate regression analysis to assess the dependence of the parameters of cholesterol biosynthesis/absorption on components of MetS including serum uric acid (SUA), apolipoprotein B (apoB), and age. Results: In CMR group, higher lathosterol to total plasma cholesterol (TC) ratio (LCR) was influenced by gender (P = 0.05, analysis of covariance [ANCOVA] for age), whereas ratios of campesterol (ß-sitosterol, respectively) to TC were lower in CMR group (P < 0.001 and P = 0.002, ANCOVA for age). In men, LCR was positively associated with SUA, apoB, and hypertension (all P < 0.05). Lathosterol to campesterol or ß-sitosterol ratios were highly dependent on SUA (both P < 0.01), the former being dependent also on apoB (P < 0.01). In women, these parameters were only weakly dependent on SUA. Conclusions: These results show that the concentration of SUA in men of CMR group is associated with the indices of de novo cholesterol biosynthesis. This association is probably influenced by interaction of arterial hypertension and apoB levels with cholesterol homeostasis.

Lipid Metabolism in Patients with End-Stage Renal Disease: A Five Year Follow-up Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) exhibit high morbidity as well as mortality for atherosclerotic cardiovascular diseases (CVD). Therefore, we investigated differences in individual lipoprotein classes and subclasses in ESRD patients under chronic high volume hemodiafiltration (HV-HDF) in comparison with a control group. We also assessed the prognosis of these patients and analyzed these parameters after 5 years follow-up. METHODS: 57 patients and 50 controls were enrolled. We analysed high density (HDL) and low density (LDL) lipoprotein subfractions using the Quantimetrix Lipoprint(R) system. Subfractions were correlated with selected clinical-biochemical parameters including risk factors for atherosclerotic CVD at the beginning of and after 5 years follow-up. RESULTS: Fourteen patients survived the 5-year follow-up. Follow-up results revealed a shift toward smaller HDL subfractions. In lipoproteins carrying apolipoprotein B, there was a shift of cholesterol from very low density (VLDL) to intermediate density (IDL) lipoproteins and LDLs. Hypolipidaemic therapy did not influence lipoprotein profiles in HV-HDF patients. CONCLUSION: 1. HV-HDF patients exhibit specific lipid profiles with elevated triacylglycerol, low HDL and LDL and higher content of cholesterol in remnant particles (VLDL and IDL) at the expense of large LDL. HDL subfractions were linked to the number of risk factors for CVD in the control group only. 2. Baseline lipoprotein profiles did not differ between survivors and non-survivors. Non-survivors had higher CRP and lower HDL-C. 3. During the 5 year follow-up period, cholesterol in HDL particles and lipoproteins carrying apolipoprotein B redistributed in survivors towards smaller particles, thus resembling the profile of control patients.

Altered activities of antioxidant enzymes in patients with metabolic syndrome.

OBJECTIVE: In the pathogenesis of the metabolic syndrome (MetS), an increase of oxidative stress could play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of our study was to assess several parameters of the antioxidant status in MetS. METHODS: 40 subjects with MetS and 40 age- and sex-matched volunteers without MetS were examined for activities of superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), paraoxonase1 (PON1), concentrations of reduced glutathione (GSH), and conjugated dienes in low-density lipoprotein (CD-LDL). RESULTS: Subjects with MetS had higher activities of CuZnSOD (p < 0.05) and GR (p < 0.001), higher concentrations of CD-LDL (p < 0.001), lower activities of CAT (p < 0.05) and PON1 (p < 0.05), and lower concentrations of GSH (p < 0.05), as compared with controls. Activity of GPX1 was not significantly changed. CONCLUSIONS: Our results implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (triglycerides, high-density lipoprotein cholesterol (HDL-C)) and clinical (waist circumference, blood pressure) components of MetS.

N-3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia.

BACKGROUND: Atherogenic dyslipidemia contributes substantially to the residual cardiovascular risk. The aim of this study was to examine the effects of therapeutic doses of n-3 polyunsaturated fatty acids on the three major lipid abnormalities of atherogenic dyslipidemia, i.e. hypertriacylglycerolemia, low HDL cholesterol, and increased levels of small dense LDL particles, as well as on some new risk factors. MATERIALS AND METHODS: A total of 60 hypertriacylglycerolemic patients were included in the study. Group S consisted of 36 patients who were already treated with statins, Group N of 24 patients not yet treated. Each patient was examined after six weeks on placebo and six weeks of treatment with n-3 PUFA (eicosapentaenoic and docosahexaenoic acid ethyl esters, 3.0 g/d). RESULTS: Treatment with n-3 PUFA caused a decrease in plasma triacylglycerols (28%, p<0.001), and VLDL (-27%, p<0.001), an increase in HDL-C (+4%, p<0.01), and a decrease in sdLDL cholesterol (-16%, p<0.05). These changes were accompanied by a decrease in microalbuminuria (-30%, p<0.05), as well as in several parameters of oxidative stress. Analysis of the fatty acids composition of plasma phospholipids showed a significant increase in all n-3 PUFAs examined, accompanied by a decrease in n-6 PUFAs, as well as in monounsaturated acids. No significant differences in the effects of n-3 PUFA were found between the Groups S and N. CONCLUSION: Our results support the opinion that hypertriacylglycerolemic patients benefit from the treatment with n-3 PUFA which improves several important metabolic factors of cardiovascular risk.

[Shy-Drager syndrome]. / Shyuv-Drageruv syndrom.

Shy-Drager syndrome is a rare neurological disease with a poor prognosis causing a generalised autonomy dysfunction. The disorder is also known as multiple system atrophy, the orthostatic hypotension syndrome or Shy-McGee-Drager syndrome. Patients have mainly dysautonomic symptoms. Patients suffer from orthostatic hypotension, bradycardia, anhidrosis, failure of accommodation, sialoporia, low tears secretion, gastrointestinal dysmotility and incomplete emptying of the urinary bladder. Neuropathological examination of patient's brains demonstrated neurodegenerative changes of the structures of central nervous system, mainly of brainstem. The Shy-Drager syndrome results from striatonigral and olivo-ponto-cerebellar atrophy and from accumulation of alpha-synuclein in these structures. The patients suffering from the Shy-Drager syndrome are very often misdiagnosed because of overlap of symptomatology with psychiatric and psychosomatic diseases. It is also very difficult to make the diagnosis because of complexity of symptoms. The prognosis of Shy-Drager syndrome is very poor; patients are markedly disabled and have shorter survival.