Search

Background: data regarding the association between obesity and morbidity/mortality in patients with chronic kidney disease (CKD) are uncertain and sometimes contradictory. The aims of our study were to determine the associations among different measures of obesity and adiposity, and the risk of all-cause mortality or dialysis entry in stage 3–5 CKD patients. Materials: this observational cohort study included 178 CKD patients followed for a median of 71 months. Biochemistry, anthropometric measures such as body mass index (BMI), waist-to-hip ratio, mid-arm muscle circumference (MAMC) and body composition by bioimpedance analysis were evaluated. Results: we found a weak agreement between BMI and other measures of adiposity. In multivariable regression analysis, all measures of obesity such as BMI, waist circumference and waist-to-height ratio were not associated with dialysis entry and/or mortality. Instead, MAMC was associated with dialysis entry HR 0.82 [95% CI: 0.75–0.89] and high FM% with mortality HR 2.08 [95% CI: 1.04–4.18]. Conclusions: in our CKD population, lower MAMC was predictive of dialysis commencing, while a higher percentage of fatty mass was a predictor of mortality. Instead, obesity, as defined by BMI, is not associated with dialysis commencing or all-cause mortality. [ABSTRACT FROM AUTHOR]

Hyporesponsiveness to erythropoietin stimulating agents (ESAs) is a condition associated with increased mortality. Even after identifying the condition, the causes are difficult to treat and only partially reversible in end-stage renal disease patients. Thus, the role of more recent hemodialysis (HD) techniques in improving such conditions is an emerging issue. However, major randomized clinical trials have not confirmed the results of smaller observational studies in which online hemodiafiltration has shown some efficacy in improving patients’ response to ESAs. In our interpretation, these findings are not in contrast, but they can be explained by a better understanding of the interactions between HD and ESAs on iron mobilization, first of all through the role of hepcidin. The kinetics of hepcidin removal through HD combined with the action of selected ESAs may help the clinician in prescribing the best association between HD treatment and ESAs to overcome hyporesponsiveness. [ABSTRACT FROM AUTHOR]

Background. We tested the hypothesis that soluble CD40 ligand (sCD40L), a biomarker of proatherogenic inflammation, may be predictive of cardiovascular (CV) events in a subgroup of patients from the RISCAVID study, an observational and prospective study in patients on haemodialysis (HD).Methods. Plasma sCD40L levels were assessed at the time of the enrollment in 300 HD patients (mean age: 65 ± 15 years), recruited in five different centres. During a follow-up of 24 months, overall mortality, CV mortality and CV major nonfatal events (acute myocardial infarction, congestive heart failure and stroke) were registered. Cox proportional hazards regression assessed adjusted differences in CV morbidity and mortality risk.Results. Stratifying patients according to plasma sCD40L levels in those with levels lower or equal to (sCD40L−) and greater than (sCD40L+) the median value of 7.6 ng/mL, no significant difference was observed at baseline between the two groups in age, gender, blood pressure values and previous CV events. At 24-month follow-up, a significant (P < 0.01) lower incidence of the combined end point of CV morbidity and mortality was observed in the sCD40L− group (29%) as compared to the sCD40L+ group (36%). In the multivariate Cox proportional hazards regression model, the presence of sCD40L above the median value is associated with a significant increase in the risk of CV morbidity and mortality (hazard ratio: 1.61, 95% confidence interval 1.03–3.11).Conclusions. These observational results support the prognostic value of sCD40L in end-stage renal disease, thus providing a useful tool to better stratify CV prognosis in these patients. [ABSTRACT FROM PUBLISHER]

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53 ± 5.8 years with a mean creatinine clearance (CCr) of 52 ± 37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0 ± 4.6 mg/L and 5.8 ± 5.6 pg/mL, respectively and were not significantly correlated (r = 0.11, p = n.s.). CRP and IL-6 were however related with renal function (CRP versus CCr r = -0.40 p < 0.001; IL-6 versus CCr r = -0.45; p < 0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4 ± 6.3 mg/L in the group of patients with a CCr lower than 20 mL/min (n = 32) and 2.76 ± 4.35 in the group of patients with a CCr higher than 20mL/min (n = 70) (p < 0.0001). CRP and IL-6 were positively related with ESR (r = 0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2 ± 0.4 versus 3.0 ± 0... [ABSTRACT FROM AUTHOR]

Calcitriol modulates in vivo and in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37° for 12 hours with 100 ng of LPS (E. coli and P. maltofilia ). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-α and IL-1β were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-α and IL-1β production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 μg/week). Intracellular calcium [Ca++ ]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro , TNF-α increased from 3.6 ± 1.9 pg/cell to 1797 ± 337 in N, from 4.5 ± 1.7 to 1724 ± 232 in CRF and from 3.4 ± 2.3 to 1244 ± 553 in HD after the LPS stimulus. The production of TNF-α was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 ± 2.1 in N, 3.7 ± 1.9 in CRF and 3.4 ± 1.7 in HD; LPS + Vit.D3 50 ng, 263 ± 296 (N), 6.73 ± 11 (CRF), 38 ± 28 (HD); LPS + Vit.D3 25 ng = 873 ± 583 (N), 325 ± 483 (CRF), 588 ± 507 (HD); LPS + Vit.D3 12.5 ng, 954 ± 483 (N), 912 ± 510 (CRF), 875 ± 527 (HD)]. Comparable data were observed on IL-1β production. In vivo , the intradialytic TNF-α... [ABSTRACT FROM AUTHOR]

Background: Cohort studies have demonstrated an association between C-reactive protein (CRP) and interleukin-6 (IL-6) and all-cause and cardiovascular mortality in end-stage renal disease (ESRD) patients. Interleukin-8 (IL-8) appears to be not only the plasma expression of the acute-phase response but also a direct pathogenetic mediator of the atherosclerotic process. Methods: To evaluate the role of IL-8 in predicting outcome, 76 chronic dialytic patients were prospectively followed for 18 months. At baseline, blood samples were taken for analysis of high-sensitivity CRP, IL-6, IL-8 and other standard laboratory analyses. Results: Median IL-8 was 5.2 mg/l, therefore near half of the patients had IL-8 values within the range of ‘normal limits’. IL-6 and CRP were significantly correlated (r = 0.45, p < 0.001) and a positive correlation was also found between IL-6 and IL-8 (r = 0.39, p < 0.001). The correlation coefficient between IL-6 and CRP was 0.43 (p < 0.001) and 0.50 (p < 0.001) in patients without and with history and/or clinical signs of cardiovascular disease, respectively. After a follow-up of 1.5 years, 8 patients had died from cardiovascular causes and another 7 patients for other reasons; furthermore 9 major nonfatal cardiovascular events were recorded. Stepwise regression analysis showed IL-8 as the strongest independent predictor of all-cause and cardiovascular events (p = 0.0025) even after adjustment for age and dialytic age, followed by IL-6 and CRP (p < 0.01). Conclusion: Despite a small population and a relatively short follow-up period, this study firstly demonstrated that IL-8 is a powerful independent predictive factor for cardiovascular and overall mortality cause in ESRD patients. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Decreased inflammation and cardiovascular mortality are evident in patients with end-stage chronic kidney disease treated by online hemodiafiltration. Extracellular vesicles (EV) are mediators of cell-to-cell communication and contain different RNA types. This study investigated whether mixed online hemodiafiltration (mOL-HDF) beneficial effects associate with changes in the RNA content of plasma EV in chronic kidney disease patients. Thirty bicarbonate hemodialysis (BHD) patients were randomized 1:1 to continue BHD or switch to mOL-HDF. Concentration, size, and microRNA content of plasma EV were evaluated for 9 mo; we then studied EV effects on inflammation, angiogenesis, and apoptosis of endothelial cells (HUVEC) and on osteoblast mineralization of vascular smooth muscle cells (VSMC). mOL-HDF treatment reduced different inflammatory markers, including circulating CRP, IL-6, and NGAL. All hemodialysis patients showed higher plasma levels of endothelial-derived EV than healthy subjects, with no significant differences between BHD and mOL-HDF. However, BHD-derived EV had an increased expression of the proatherogenic miR-223 with respect to healthy subjects or mOL-HDF. Compared with EV from healthy subjects, those from hemodialysis patients reduced angiogenesis and increased HUVEC apoptosis and VSMC calcification; however, all these detrimental effects were reduced with mOL-HDF with respect to BHD. Cell transfection with miR-223 mimic or antagomiR proved the role of this microRNA in EV-induced HUVEC and VSMC dysfunction. The switch from BHD to mOL-HDF significantly reduced systemic inflammation and miR-223 expression in plasma EV, thus improving HUVEC angiogenesis and reducing VSMC calcification. [ABSTRACT FROM AUTHOR]