Plasma adiponectin levels in chronic kidney disease patients: relation with molecular inflammatory profile and metabolic status.

BACKGROUND AND AIM: Adiponectin (ADPN) exerts anti-inflammatory and cardio protective effects and is associated with decreased cardiovascular risk, however its role in patients with chronic kidney disease is unclear. METHODS AND RESULTS: We investigated the correlation between plasma ADPN levels, the progression of CVD and CKD and the inflammatory gene expression profile of peripheral blood mononuclear cells in patients from the NephroPLIC study (a prospective study aimed at addressing the progression of cardiovascular damage in relation to kidney dysfunction). Plasma ADPN levels were directly correlated with age, HDL-C and creatinine, and inversely with BMI, triglycerides and glomerular filtration rate (GFR). Multiple regression analysis identified plasma creatinine and HDL as the independent factors associated with ADPN plasma levels. In peripheral blood mononuclear cells (PBMC), the mRNA expression of MCP-1, CD40, Cox-2, TLR4, PAI-1, TNF alpha, resistin and RAGE was up-regulated in the group with higher GFR and higher ADPN plasma levels compared to that with low GFR and ADPN plasma levels. Patients with similar GFR values showed no differences in the gene expression profile of PBMC although ADPN levels were associated with decreased CRP and IL-6 plasma levels and decreased IMT and heart left ventricular mass. CONCLUSION: In CKD patients who are not in dialysis ADPN plasma levels are associated with a reduced renal excretory function, but correlate inversely with the determinants of the metabolic syndrome such as glucose, triglycerides and BMI, and directly with HDL. Furthermore, in patients with a similar degree of renal impairment, ADPN plasma levels are associated with a better cardiometabolic profile, despite no significant difference being observed in the gene expression pattern of PBMC.

Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction.

OBJECTIVE: Resistin is an adipokine that has been suggested to be correlated with markers of inflammation and to be predictive of coronary atherosclerosis and type II diabetes in humans. A common single nucleotide polymorphism (SNP) (-420C/G) in the promoter of resistin is associated with increased resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of the -420C/G polymorphism with metabolic syndrome, obesity, myocardial infarction and kidney disease. DESIGN AND RESULTS: First we studied 1542 subjects from the PLIC study (a population based cohort). GG carriers showed an higher prevalence of obesity and metabolic syndrome as well as increased plasma triglycerides levels, BMI, systolic and diastolic blood pressure and cardiovascular risk according to Framingham algorithm (P < 0.05 for all). Next we investigated the presence of the -420C/G resistin polymorphism in a case-control study that included 300 subject with myocardial infarction and 300 age and sex matched controls and then we studied the role of the -420C/G SNP in 88 patients with mild to moderate renal dysfunction. No statistically significant differences in allele frequencies between the PLIC study, the myocardial infarction (MI) cases and the subjects with renal dysfunction were observed. Pro-inflammatory gene expression profiling of peripheral blood mononuclear cells failed to detect any difference between wild type subjects and carriers of the rare allele. CONCLUSION: Our data suggest that the presence of the -420C/G SNP of the resistin gene is associated with increased obesity and metabolic syndrome, although it is not different in subjects at high cardiovascular risk such as patients with myocardial infarction or patients with renal dysfunction compared with controls.

Plasma resistin levels correlate with determinants of the metabolic syndrome.

OBJECTIVE: The role of resistin in insulin sensitivity and obesity is controversial. Some authors suggest that increased serum resistin levels are associated with obesity, visceral fat, insulin resistance, type 2 diabetes and inflammation, while others failed to observe such correlations. The aim of the present study was to investigate the relationship of plasma resistin levels with markers of the metabolic syndrome and atherosclerosis in a large population-based study. DESIGN AND PATIENTS: Plasma resistin levels were determined in 1090 subjects free of any medication selected from the PLIC study (designed to verify the presence of atherosclerotic lesions and progression intima-media thickness (IMT) in the common carotid artery in the general population) and related to the presence of obesity, metabolic syndrome, metabolic abnormalities, cardiovascular risk, and progression of IMT. RESULTS: Plasma resistin levels were highly positively correlated with triglycerides, waist circumference, waist/hip ratio, systolic blood pressure, and ApoAI/ApoB ratio, while they were inversely correlated with high density lipoprotein and ApoAI levels. This finding was gender specific (mainly in women). Plasma resistin levels were significantly higher in women with the metabolic syndrome compared with controls (4.90 (0.24) ng/ml vs 3.90 (0.11) ng/ml; P<0.01), while no difference was observed in obese subjects. Finally, plasma resistin levels were significantly correlated with cardiovascular risk calculated according to the Framingham algorithm (P<0.01). CONCLUSION: Plasma resistin levels are increased in presence of the metabolic syndrome and are associated with increased cardiovascular risk.

Role of vitamin E-coated membrane in reducing advanced glycation end products in hemodialysis patients: a pilot study.

INTRODUCTION: Advanced glycation end products (AGEs) are markers of oxidative stress. AIMS: To assess if a vitamin-E-coated dialyzer affects plasma AGE levels and endothelial function in hemodialysis patients. METHODS: 16 patients were dialyzed with a synthetic modified cellulose membrane (SMC, n = 8) or a vitamin E-coated dialyzer (n = 8), respectively. At week 32 endothelial function was determined as brachial artery flow-mediated dilatation (FMD). Total AGEs, free pentosidine (FP), protein-bound pentosidine (BP) and autoantibodies against oxidized LDL (ox-LDL-autoantibodies) were assessed at baseline (T0) and at 16, 32, 40 and 42 weeks (T16, T32, T40 and T42). RESULTS: At T16 and T32 FP and BP were lower in vitamin E than in SMC (T 16: 88.7 +/- 8.96 vs. 124.2 +/- 11.90 pmol/ml plasma; p = 0.04, and 22.9 +/- 2.99 vs. 32.8 +/- 2.98 pmol/mg proteins; p = 0.04. T32: 78.7 +/- 8.54 vs. 123.7 +/- 10.15 pmol/ml plasma; p = 0.007, and 19.9 +/- 2.0 vs. 33.67 +/- 2.41 pmol/mg proteins; p = 0.001). In vitamin E, AGEs were lower at T32, T40 and T42 (946.7 +/- 80.91 vs. 1,351.2 +/- 179.33 AU/ml, p = 0.05; 986.9 +/- 59.63 vs. 1,509.9 +/- 154.17 AU/ml, p = 0.013; 890.3 +/- 73.70 vs. 1,453.9 +/- 153.16 AU/ml, p = 0.009). At T32 AGEs, ox-LDL autoantibodies and FMD were inversely correlated (R = -0.70 p = 0.007 and R = -0.59, p = 0.04, respectively). CONCLUSIONS: Vit E-coated membrane reduces plasma AGEs levels and AGEs values are negatively correlated with FMD.

Triglyceride-rich lipoproteins from hypertriglyceridemic subjects induce a pro-inflammatory response in the endothelium: Molecular mechanisms and gene expression studies.

Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study we investigated the effects of TGRLs from type IV hyperlipidemic and normolipidemic subjects on endothelial activation focusing on the effects on intracellular pathways and gene expression. A total of 54 subjects, 30 hypertriglyceridemic (triglyceride (TG) levels 284+/-101 mg/dl) and 23 normotriglyceridemic (TG levels 109+/-40 mg/dl) were enrolled as lipoprotein donors. TGRLs were isolated from hypertriglyceridemic (H-TGRL) and normotriglyceridemic (N-TGRL) subjects. RNA from human endothelial cells incubated with N-TGRL or H-TGRL was prepared for cDNA microarray analyses. Western blotting was used to study intracellular signaling pathways. Regulated genes were further studied with real-time PCR, immunofluorescence and FACS. Furthermore, a protein/DNA array and chromatin-immunoprecipitation were used to identify transcription factors involved in the observed effects. Both N-TGRL and H-TGRL activated ERK1/2 and p38 MAPK. However, there were differences in the pattern of upregulated target genes between the two types of lipoproteins in HUVECs and/or HAECs: PAI-1, VCAM-1, ELAM-1 and MCP-1 were upregulated by both N-TGRL and H-TGRL, while PECAM-1, IL-6 and ADAMTs1 were selectively upregulated by H-TGRL. Chromatin immunoprecipitation analysis demonstrated the involvement of transcription factors NF-kB and CREB in the activation of these genes. These results support the possible involvement of hypertriglyceridemic TGRLs in endothelial dysfunction via induction of a pro-inflammatory and pro-thrombotic state.

Effect of the Toll-like receptor 4 (TLR-4) variants on intima-media thickness and monocyte-derived macrophage response to LPS.

OBJECTIVES: Toll-like receptor 4 (TLR-4) is believed to contribute to the initiation and progression of atherosclerosis. The association of the D299G polymorphism of the TLR-4 gene with the progression of coronary and carotid atherosclerosis, risk of cardiovascular events and myocardial infarction is controversial. We have investigated whether the presence of the D299G polymorphism and the co-segregated T399I polymorphism affects the intima-media thickness (IMT) in the general population. SUBJECTS: The PLIC study population (n = 1256) was genotyped for the D299G and the T399I polymorphisms. RESULTS: The presence of both the D299G and T399I alleles was observed in the 13.0% of the population, carriers of the T399I alone were 1.8% and of the D299G alone were 0.9%. No difference in IMT was detected within the carriers of the D299G and T399I alleles and the wild-type subjects in the PLIC population. Furthermore, we investigated whether monocyte from D299G to T399I subjects present a defective response to CD40, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, cyclo-oxygenase (COX)-2 and PTX3 expression induced by lipopolysaccharide (LPS). When the monocyte-derived macrophages of these subjects were challenged with LPS (1 mug mL(-1)), no impact of the polymorphisms on the induction of CD40, MCP-1 and PTX3 was observed. Only IL-6 and COX-2 induction by LPS resulted reduced in the D299G/T399I carriers. CONCLUSION: The presence of the D299G and T399I polymorphisms of the TLR-4 gene does not play a major role on the progression of carotid atherosclerosis. Macrophages from the subjects carrying the polymorphisms show an impaired response to LPS limited only to a IL-6 and COX-2.

Deficiencias de hierro y de vitamina A y prevalencia de anemia en niños y niñas de 6 a 24 meses de edad en Chaco, Argentina / Iron and vitamin A deficiencies and prevalence of anemia in boys and girls between 6 to 24 months of age in Chaco, Argentina

To determine the prevalence of anemia, and iron (ID) and vitamin A deficiencies aiming at their prevention, 414 children between 6 and 24 months of age, were randomly selected from the whole province of Chaco. A sociodemographic survey was implemented, and hemoglobin (Hb), plasma ferritin and retinol were measured. Anemia prevalence (Hb < 110 g/L) was 66.4 per cent, without differences between age groups, and included 18 per cent with Hb < 90 g/L. These cases were significantly less in children 6-8 month of age (5.1 per cent) than in the others (approximately equal to 20 per cent) (P: 0.007). Mean Hb was also higher in 6-8 months old children and was associated with lower prevalence of ID (ferritin < 12 micrograms/L) (p < 0.000) but not with age (p = 0.8865). ID already present, however, in 36.6 per cent of children in this age group, reached a prevalence of 72.9 per cent in children older than 18 months. Anemia prevalence was significantly higher in males, in children whose birth weight was < 3000 g, in those who had never taken iron supplements and among the poor, both structural and by income. Retinol values < 20 micrograms/dl occurred only in 5.1 per cent of children. Iron nutrition prior to, during pregnancy and in children during the first 2 years of life must be improved by joining strategies based on community empowerment aimed at improving dietary iron, assuring effective preventive supplementation and promoting the opportune umbilical cord ligation.

Deficiencia de hierro y anemia en mujeres embarazadas en Chaco, Argentina / Iron deficiency and anemia in pregnant women from Chaco, Argentina

Aiming at their prevention, to determine the prevalence of gestational iron deficiency and anemia, considering access to health care and associations with social and biological variables in the Province of el Chaco, Argentina. Three hundred and sixty four, randomly selected pregnant women from the whole province participated. Mean Hemoglobin (Hb) +/- SD dropped progressively from 118.4 +/- 11.0 to 112.1 +/- 11.5 g/L (p = 0.015) between the 1st and the 3rd gestational trimesters. Anemia prevalence (Hb < 110 g/L) was 17.4, 26.5 and 35.8 per cent. From the 1st to the 3rd trimesters. Second trimester prevalence was 14.1 per cent using Hb < 105 g/L as recently suggested. The ferritin geometric mean during the progressive gestational trimesters were 28.9; 16.0 and 11.1 micrograms/L. 21.7, 40.5 and 60.5 per cent had ferritins < 12 micrograms/L, and 39.1, 58.9 and 83.2 per cent had ferritins < 20 micrograms/L in these respective trimesters (p < 0.004 between trimesters in both cases). Both iron deficiency and anemia were significantly greater in women with unfinished primary education and with interpregnancy interval < 1 year. Seventy five percent of women had adequate number of antenatal visits but only 23 per cent were taking iron supplements and 10 per cent had stopped taking them. The prevention and correction of gestational iron deficiency and anemia must focus on the preconceptional period (inter-pregnancy spacing and increasing iron intake using all available means) as well as during pregnancy improving adherence to iron supplements by means of motivation of health workers and community.