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.

Methylation status of immune response genes promoters in cell-free DNA differs in hemodialyzed patients with diabetic nephropathy according to the intensity of anemia therapy.

BACKGROUND: Anemia is a major complication of end-stage renal disease. Hemodialysis itself is regarded as a stimulus activating inflammation. Pro-inflammatory cytokines are able to suppress erythropoiesis. In this pilot study, we analyzed the changes in methylation status of promoters of immune response genes in cell-free DNA to detect the differences between diabetic subjects (n = 18) with different therapeutic doses of recombinant erythropoietin. METHODS: The extent of promoter methylation of 24 genes in plasma cell-free DNA was examined before and after hemodialysis using EpiTect Methyl qPCR Array Inflammatory Response and Autoimmunity (Qiagen). RESULTS: The patients with higher methylation status of gene sequences IL13RA1, IL15, EDG3 and INHA in interdialytic interval were significantly overrepresented in the group with none or mild anemia therapy. CONCLUSION: The results are in agreement with the fact that IL13 and IL15 are known inhibitors of erythropoiesis and with considered immunomodulatory role of cell-free DNA.

Alterations in methylation status of immune response genes promoters in cell-free DNA during a hemodialysis procedure.

OBJECTIVE: Elevations of cell-free DNA (cfDNA) concentrations during hemodialysis (HD) sessions were reported in numerous studies regardless of an applied therapeutic protocol. It is generally thought that the elevated concentrations represent the consequence of apoptosis on the dialysis membranes. No data concerning the qualitative characteristics of cfDNAs in HD patients have been published till today; therefore, we focus on the promoter methylation status of genes involved in immune response. RESEARCH DESIGN AND METHODS: We isolated cfDNA from randomly selected patients before and after a HD session and from healthy subjects examined two times per day with 4 h interval. The extent of promoter methylation of 24 genes involved in immune response was examined using the 'EpiTect Methyl qPCR Array Inflammatory Response and Autoimmunity'. RESULTS: In our pilot study, we discovered significant changes in methylation patterns of genes IL-7, IL-13, IL-17C and TYK2 between HD patients and healthy subjects. CONCLUSION: Methylation of immune response genes promoters may be detected using EpiTect Methyl qPCR Array Inflammatory Response and Autoimmunity at the level of cfDNA to provide the information about the actual state of immune response in HD patients.

Low-flow polytetrafluoroethylene accesses: ultrasound surveillance and preemptive interventions ensure long-term patency.

BACKGROUND: Vascular accesses (especially polytetrafluoroethylene grafts) with a permanently low flow (Qa <600 ml/min) are prone to thrombosis and thus have short patency. The reason for a permanently low flow is usually medial calcinosis of the inflow artery in diabetics. We retrospectively studied the long-term patency of low-flow grafts with careful ultrasound surveillance and preemptive interventions. METHODS: Twenty subjects with Qa permanently <600 ml/min were included. Ultrasound surveillance was performed every 3 months in addition to classical monitoring techniques. Significant stenosis was strictly defined as the combination of B-mode narrowing >50% + >2-fold peak systolic velocity increase + 1 additional criterion (residual diameter <2.0 mm or flow volume decrease by >20%). Such stenoses were treated by preemptive percutaneous intervention. Primary and secondary patencies were calculated. RESULTS: The primary patency was 357 ± 316 days and the secondary (cumulative) patency was 996 ± 702 days. The number of interventions was 2.09/patient year, but >10 in 6 (33%) subjects. 93 and 80% of grafts were patent 1 and 2 years after access creation, respectively. CONCLUSION: Low-flow accesses undergoing ultrasound surveillance with strict diagnostic criteria and preemptive interventions had patencies similar to accesses with normal Qa in our study. This was enabled by a relatively high rate of interventions.

Short-term outcomes of borderline stenoses in vascular accesses with PTFE grafts.

BACKGROUND: There are controversial data about vascular access stenosis surveillance by ultrasonography. The definition of stenosis significance varies among centres. We performed a retrospective study to describe short-term outcomes of borderline asymptomatic stenoses defined by precise criteria and to determine possible risk factors of stenosis progression. METHODS: We studied the outcome of borderline stenoses in accesses with PTFE grafts. Stenosis was considered significant if there was a combination of >50% lumen reduction and peak systolic ratio >2, together with at least one of the following additional criteria: (1) residual diameter <2.0 mm and (2) flow reduction of >25% or actual flow volume <600 ml/min. Stenosis was considered borderline in the absence of the additional criteria. RESULTS: Of the 102 borderline stenoses, after 11 +/- 6 weeks, 55 remained non-progressive, in 38 the degree of the stenosis progressed, in 8 a percutaneous transluminal angioplasty (PTA) was performed due to clinical indication and only 1 thrombosed. A significant relative risk of developing significant stenosis was found in grafts with prior PTA [RR = 1.91 (95% CI: 1.27, 2.88), P = 0.002] and in female gender [RR = 2.29, (95% CI: 1.29, 4.06), P = 0.025]. CONCLUSIONS: Delaying PTA of borderline stenoses is safe using this watch-and-wait strategy and stenoses remain stable over at least short time, but with higher risk of progression especially after prior PTA. We believe that the definition of precise criteria of stenosis significance is necessary for the benefit of ultrasound surveillance.

Ghrelin variants influence development of body mass index and plasma levels of total cholesterol in dialyzed patients.

BACKGROUND: Ghrelin is an endogenous hormone expressed predominantly in the stomach. Ghrelin controls growth hormone secretion and also affects the body's energy balance. We analyzed the association of ghrelin variants with body mass index (BMI), albumin as a marker of malnutrition and plasma lipids as risk factors for atherosclerosis in hemodialyzed patients, in whom malnutrition and accelerated atherosclerosis are common complications. METHODS: Ghrelin variants Arg51>Gln and Leu72> Met were analyzed by PCR-RFLP in 210 hemodialyzed patients, prospectively followed up for 15 months. Changes in body mass index, triglycerides, total cholesterol and albumin over time (after 3, 6, 9, 12 and 15 months of dialysis) were analyzed in subgroups divided according to ghrelin genotypes. RESULTS: Carriers of at least one of the Gln51 and Met72 alleles lost body weight more quickly than Arg51Arg/Leu72Leu homozygotes (p<0.01). Carriers of the Gln51 allele were at higher risk of developing high cholesterol levels (p<0.01). CONCLUSIONS: Common ghrelin variants may have an effect on changes in biochemical and anthropometric parameters in hemodialyzed patients over time and could be used in the future to plan individualized therapy.