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Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD.

Cardiovascular disease (CVD) events are the main causes of death in end-stage renal disease (ESRD) patients on dialysis. The number and severity of CVD events remain inappropriate and difficult to explain by considering only the classic CVD risk factors. Our aim was to clarify the changes and the relationship of lipoprotein subfractions with other CVD risk factors, namely, body mass index (BMI) and adipokines, inflammation and low-density lipoprotein (LDL) oxidation, and the burden of the most prevalent comorbidities, diabetes mellitus (DM) and hypertension (HT). We studied 194 ESRD patients on dialysis and 22 controls; lipid profile, including lipoprotein subpopulations and oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, leptin, and paraoxonase 1 activity were evaluated. Compared to controls, patients presented significantly lower levels of cholesterol, high-density lipoprotein cholesterol (HDLc), LDLc, oxLDL, and intermediate and small HDL and higher triglycerides, CRP, adiponectin, large HDL, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein- (IDL) B. Adiponectin levels correlated positively with large HDL and negatively with intermediate and small HDL, oxLDL/LDLc, and BMI; patients with DM ( n = 17) and with DM+HT ( n = 70), as compared to patients without DM or HT ( n = 69) or only with HT ( n = 38), presented significantly higher oxLDL, oxLDL/LDLc, and leptin and lower adiponectin. Obese patients ( n = 45), as compared to normoponderal patients ( n = 81), showed lower HDLc, adiponectin, and large HDL and significantly higher leptin, VLDL, and intermediate and small HDL. In ESRD, the higher adiponectin seems to favor atheroprotective HDL modifications and protect LDL particles from oxidative atherogenic changes. However, in diabetic and obese patients, adiponectin presents the lowest values, oxLDL/LDLc present the highest ones, and the HDL profile is the more atherogenic. Our data suggest that the coexistence of DM and adiposity in ESRD patients on dialysis contributes to a higher CVD risk, as showed by their lipid and adipokine profiles.

To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.

Background: End-stage renal disease (ESRD) patients under hemodialysis (HD) have high mortality rate. Inflammation, dyslipidemia, disturbances in erythropoiesis, iron metabolism, endothelial function, and nutritional status have been reported in these patients. Our aim was to identify any significant association of death with these disturbances, by performing a two-year follow-up study., Methods and Results: A large set of data was obtained from 189 HD patients (55.0% male; 66.4 ± 13.9 years old), including hematological data, lipid profile, iron metabolism, nutritional, inflammatory, and endothelial (dys)function markers, and dialysis adequacy., Results: 35 patients (18.5%) died along the follow-up period. Our data showed that the type of vascular access, C-reactive protein (CRP), and triglycerides (TG) are significant predictors of death. The risk of death was higher in patients using central venous catheter (CVC) (Hazard ratio [HR] = 3.03, 95% CI = 1.49-6.13), with higher CRP levels (fourth quartile), compared with those with lower levels (first quartile) (HR = 17.3, 95% CI = 2.40-124.9). Patients with higher TG levels (fourth quartile) presented a lower risk of death, compared with those with the lower TG levels (first quartile) (HR = 0.18, 95% CI = 0.05-0.58)., Conclusions: The use of CVC, high CRP, and low TG values seem to be independent risk factors for mortality in HD patients.

Objective: To evaluate the effect of gender and menopause in cardiovascular risk (CVR) in a healthy population based on both classical and nontraditional markers., Methods: 56 men and 68 women (48 pre- and 20 postmenopause) were enrolled in the study. The following markers were analyzed: blood pressure (BP), body mass index (BMI), waist circumference (WC), glucose, total cholesterol (total-c), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-c), oxidized-LDL (Ox-LDL), HDL-c and subpopulations, paraoxonase-1 activity, hsCRP, uric acid, tumor necrosis factor alpha (TNF- α ), adiponectin, vascular endothelial growth factor (VEGF), and intercellular adhesion molecular 1 (ICAM1)., Results: Relative to the women, men present significantly increased BMI, WC, BP, glucose, total-c, TGs, LDL-c, Ox-LDL, uric acid, and TNF- α and reduced adiponectin and total and large HDL-c. The protective profile of women is lost after menopause with a significantly increased BMI, WC, BP, glucose, LDL-c, Ox-LDL, hsCRP, and VEGF and decreased total and large HDL-c. Significant correlations were found in women population and in postmenopausal women between Ox-LDL and total, large, and small HDL-c and between TNF- α and total, large, and small HDL-c, LDL-c, and Ox-LDL., Conclusions: Men present higher CVR than women who lost protection after menopause, evidenced by nontraditional markers, including Ox-LDL and HDL subpopulations.

Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation.

To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL), on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), CEL: 10  mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P), and curative CEL (BBN+CEL-C) groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%), BBN 13/20(65%), CEL 0/8(0%), CEL+BBN-P 1/8(12.5%), and BBN+CEL-C 6/8(75%). The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.