THE EFFECT OF EPO TREATMENT ON INSULIN RESISTANCE AND INFLAMMATORY MARKERS IN PATIENTS ON MAINTENANCE HEMODIALYSIS (original) (raw)
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Background: The energy homeostasis-associated gene (ENHO), retinoid X receptor alpha gene (RXRA), and liver X receptor alpha gene (LXRA) are involved in adipogenic/lipogenic regulation. We investigated whether single-nucleotide polymorphisms in these genes (ENHO rs2281997, rs72735260; RXRA rs749759, rs10776909, rs10881578; LXRA rs2279238, rs7120118, rs11039155) are associated with dyslipidaemia, related comorbidities and survival of haemodialysis (HD) patients also tested for T-helper (Th) cell interleukin genes (IL). Methods: The study was carried out in 873 HD patients. Dyslipidaemia was diagnosed by the recommendations of the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines (2003); atherogenic dyslipidaemia was referred to if the TG/HDL cholesterol ratio was equal to or higher than 3.8. Genotyping of ENHO SNPs, LXRA SNPs, and IL12A rs568408 was carried out using HRM analysis. RXRA SNPs, IL12B rs3212227, and IL18 rs360719 were genotyped using PCR-RFLP analysis. The circulating adropin concentration was determined in 126 patients by enzyme-linked immunosorbent assay. Survival probability was analysed using the Kaplan-Meier method in 440 patients followed through 7.5 years.
Nephrology Dialysis Transplantation
Of 403 patients studied, mean age was 59 yrs., 56% were men, 67% were White/Hispanic, and 18% Black. K+ values in each BL and FU period are summarized in Table 1 and Figure 2. Compared with BL1, the mean K+ changes were-0.48 in FU1;-0.51 in FU2; and-0.55 in FU3 (all p<0.001). The percentages of patients with K+ 6.0 were: BL3=34.2, BL2=35.4, BL1=44.5 and FU1=26.2, FU2=23.5, FU3=24.5.The absolute percent reductions (vs. BL1) of patients with K+ 6.0 were:-26% for FU1,-28% for FU2, and-30% for FU3 (all p<0.001). CONCLUSIONS: Statistically significant and clinically meaningful reductions in mean K+ concentrations and the percentage of patients with K+ 6.0 were observed in HD patients initiating patiromer in this typical practice setting. Given the limitations of retrospective research, these findings merit additional investigation.
American Journal of Kidney Diseases, 2004
Background: Apolipoprotein E (ApoE) polymorphism has been shown to influence serum lipid parameters and ApoE levels in both healthy subjects and hemodialysis (HD) patients. Conversely, ApoE concentration significantly affects serum lipid levels in the general population, independently of ApoE polymorphism, by modulating lipoprotein production, lipolytic conversion, and receptor-mediated clearance. Therefore, studying the effect of ApoE polymorphism on serum lipid levels without taking into account ApoE levels could lead to confounding results. However, such a combined study has not been performed in HD patients to date. Methods: Three hundred one patients without diabetes on long-term maintenance HD therapy and 200 matched healthy subjects were studied. Determination of levels of fasting serum ApoE and other lipid parameters, as well as common ApoE genotypes, was performed in all subjects. Results: HD patients had a significantly lower prevalence of the ⑀4 allele and greater levels of ApoE compared with the control population. ApoE2 allele carriers had significantly lower levels of ApoB and serum total, low-density lipoprotein, and non-high-density lipoprotein cholesterol, as well as increased ApoE levels. When ApoE levels were included in analysis, ApoE levels themselves were proven to be important determinants of serum lipid levels, whereas the effect of ApoE polymorphism became more pronounced. The combination of these 2 factors explains a much greater percentage of the variation in the studied parameters than each factor alone. Conclusion: For the first time, our study provides data to support that ApoE concentration in combination with the ApoE polymorphism significantly influences serum lipid parameters in HD patients. Am J Kidney Dis 44:300-308.
Oxidative Medicine and Cellular Longevity, 2021
Soluble epoxide hydrolase 2 (EPHX2) is an enzyme promoting increased cellular apoptosis through induction of oxidative stress (OS) and inflammation. The EPHX2 gene which encodes soluble EPHX2 might be implicated in the pathogenesis and development of OS and atherosclerosis. We aimed to assess the possible association between two functional polymorphisms of the EPHX2 gene (rs2741335 and rs11780592) with oxidized LDL (ox-LDL), carotid atherosclerosis, mortality, and cardiovascular (CV) disease in 118 patients with diabetic chronic kidney disease (CKD). At baseline, ox-LDL and carotid intima-media thickness (cIMT) were evaluated and all patients were followed for seven years with outcomes all-cause mortality and CV events. rs11780592 EPHX2 polymorphism was associated with ox-LDL, cIMT, albuminuria, and hypertension. Compared to AG and GG, AA homozygotes had higher values of albuminuria, ox-LDL, and cIMT ( p = 0.046 , p = 0.003 , and p = 0.038 , respectively). These associations remaine...
Endokrynologia Polska
Introduction: Multifactorial pathogenesis of diabetic kidney disease (DKD) consists of a combination of metabolic, environmental, and genetic factors. A genome-wide association study has shown that ELMO1 is a candidate gene for DKD occurrence and progression. The aim of this study was to assess the association of a single nucleotide polymorphism (rs741301) of the ELMO1 gene with DKD in Polish patients with type 2 diabetes (T2DM). Material and methods: This was a case/control study of 272 T2DM patients with or without DKD. Patients were divided into groups depending on DKD definition according to the American Diabetes Association (ADA) and the National Kidney Foundation (NKF). The association of the rs741301 polymorphism with DKD was assessed in the whole study group as well as in the subgroups stratified according to the presence of DKD. Results: There was no association between rs741301 polymorphisms and the presence of DKD in relation to the ADA definition (p = 0.6) or the NKF definition (p = 0.5) of DKD and with estimated glomelural filtration rate (eGFR) value reflecting the stage of the chronic kidney disease (p = 0.8). Conclusions: Even though the results of this study are negative, there is still a great need for larger studies assessing the genetic susceptibility to DKD to identify patients who are particularly prone to this complication.
Apo E gene polymorphism on development of diabetic nephropathy
Cell Biochemistry and Function, 2007
Type 2 diabetes causes premature morbidity and mortality due to the complications of atherosclerosis and diabetic nephropathy (DN). Polymorphism of Apo E gene is known to influence lipid metabolism. Apo E is polymorphic, consisting of three common isoforms (e2, e3 and e4) encoded by three alleles (2, 3 and 4) in exon 4 on chromosome 19. The aim of this study was to investigate the effect of Apo E polymorphism as a prognostic risk factor for the development of DN. A total of 108 NIDDM patients were recruited from the Nephrology and Endocrinology Departments of our hospital. All subjects were divided into three groups: Group I: diabetes with nephropathy (n:37), group II: diabetes without nephropathy (n:71), group III: controls (n:46). Apo E genotypes were determined by real-time PCR. The e4 allele frequency was significantly higher ingroup I (10.8%) than in-group III (2.2%), (p < 0.05). In diabetics without nephropathy, the total cholesterol and LDL cholesterol levels were significantly lower in subjects with e2 alleles than e3 and e4 alleles. In conclusion, the present prospective study indicates that the e4 allele of the Apo E polymorphism is one of the prognostic risk factors involved in the development of DN with type 2 diabetes mellitus.
BioMed Research International, 2019
Background. To investigate the association between insulin resistance (IR) and cardiovascular disease (CVD) risks among hemodialysis patients. Methods. We conducted a cross-sectional study between 2013 and 2017, on 384 hemodialysis patients from seven hospital-based-dialysis centers. HOMA-IR is classified according to median value. The CVD risks were defined by the K/DOQI Guidelines. Logistic regression analysis was used. Results. Patients’ age was 60.9 ± 11.8, 58.1% men, and 40.3% overweight/obese. The median of HOMA-IR was 5.4, 82.8% high systolic blood pressure, and 85.7% hyperhomocysteinemia. In multivariate analysis, IR was significantly associated with higher odds of low high-density lipoprotein cholesterol, high triglyceride, and impaired fasting glucose in groups of normal weight, overweight/obese, nondiabetes, diabetes, and overall sample. IR linked with elevated high-sensitive C-reactive protein in normal weight patients (odd ratio, OR=2.21, 95% confidence interval, 1.16-4.22, p < .05), with hypoalbuminemia in normal weight patients (OR=8.31, 95% CI, 2.35-29.37, p < .01), in nondiabetes patients (OR=6.59, 95% CI, 1.81-23.95, p < .01), and overall sample (OR=3.07, 1.51-6.23, p < .01). Conclusions. The level of IR and prevalence of CVD risks were high in hemodialysis patients. IR was independently associated with CVD risks.
Hemodialysis international. International Symposium on Home Hemodialysis, 2012
Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low-density lipoprotein (ox-LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox-LDL and adiponectin were measured using enzyme-linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox-LDL/low-density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A-I, apo B, ox-LDL, and TC/high-density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox-LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).
Yonsei Medical Journal, 2005
The angiotensin-converting enzyme (ACE) gene DD homozygote has been suggested to be a significant risk factor for the progression of diabetic nephropathy. We analyzed clinical parameters and ACE genotype distribution between type 2 diabetic patients at the extremes of renal risk, i.e. an end-stage renal failure (ESRF) group (n = 103, group 1) who were on dialysis therapy due to progression of diabetic nephropathy, and a no progression group (n = 88, group 2) who had maintained normal renal function and normoalbuminuria for more than 15 years. There were no significant differences in age, sex, body mass index, HbA1c level, or lipid profiles between the two groups (p > 0.05). Group 1 had a significantly higher prevalence of hypertension [group 1: 82.5% (85/103) vs. group 2: 50.0% (44/88), p < 0.05] and diabetic retinopathy [group 1: 103/103 (100%) vs. group 2: 28/88 (31.8%), p < 0.05] than group 2. Daily urinary albumin excretion was also higher in group 1 than in group 2 [group 1: 2873 ± 2176 mg/day vs. 12 ± 7 g/day, p < 0.05]. The frequencies of the DD, ID, and II genotypes of the ACE gene in group 1 and group 2 were 26.2%, 47.6%, and 26.2%, and 7.9%, 57.9%, and 34.2%, respectively. The ACE genotype frequencies between the two groups were significantly different according to a chi-square test with Bonferroni's correction (p = 0.004). The presence of the DD genotype increased the risk of ESRF 4.286-fold compared to the II genotype [odds ratio 4.286, 95% CI 1.60-11.42, p = 0.005]. The frequency of the D-allele was higher in both male and female patients in group 1 compared to group 2, but reached statistical significance only in males [male, group 1: 50.8% vs. group 2: 35.0%, p = 0.018, female, group 1: 48.8% vs. group 2: 39.5%, p = 0.231]. This study, although limited by sample size, showed that type 2 diabetic ESRF patients more frequently expressed the DD genotype. These findings may substantiate the previously noted relationship between the ACE DD genotype and the progression of diabetic nephropathy in Korean type 2 diabetic patients.
Relationship between Apolipoprotein E polymorphism and nephropathy in type-2 diabetic patients
Diabetes Research and Clinical Practice, 2007
Twenty to forty percent of type-2 diabetic patients (DM2) present nephropathy. Genetic polymorphism of Apolipoprotein E (Apo E) has been proposed as a risk factor in the development and progression of diabetic nephropathy. The purpose of the study was to evaluate the relationship between Apo E polymorphism and presence of nephropathy in DM2 patients.