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Background Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, putting them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite the fact that an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodeling and worse CV outcomes, scarce evidence exists on their role in this setting. Methods We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectively followed (median 22 months). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results Circulating levels of all miRNAs were lower in HD patients as compared with healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (P  < .001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox regression analyses [hazard ratio (HR) ranging from 0.943 to 0.995; P  = .05 to.02] while Kaplan–Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal receiver operating characteristic–derived cut-off value (P ranging from.001 to <.0001; crude HRs 7.95 to 8.61). Conclusions Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short mid-term. Future studies on larger HD populations are needed to generalize these findings. [ABSTRACT FROM AUTHOR]

Several studies showed the association between non-traditional risk factors [proteinuria and estimated Glomerular Filtration Rate (eGFR)] and cardiovascular (CV) and renal outcomes. Nevertheless, the etiologic role of traditional CV risk factors in referred CKD patients is less defined. Herein, we examined the association between smoking habit and CV events, mortality and CKD progression. We undertook an observational analysis of 1306 stage III–V CKD patients. Smoking habit was modeled as a categorical (never, current or former smokers) and continuous (number of cigarettes/day) variable. Mean eGFR was 35.8 ± 12.5 mL/min/1.73 m2. Never, current and former smokers were 61.1%, 10.8% and 28.1%. During a median follow-up of 2.87 years, current and former smokers were at significant risk for CV events (HRs of 1.93 [95% CI, 1.18–3.16] and 1.44 [95% CI, 1.01–2.05]) versus never smokers. Current smokers were at increased mortality risk (HR 2.13 [95% CI, 1.10–4.11]). Interactions were found between former smokers and proteinuria (p = 0.007) and diabetes (p = 0.041) for renal risk, and between current smokers and male gender (p = 0.044) and CKD stage V (p = 0.039) for renal and mortality risk. In referred CKD patients, smoking habit is independently associated with CV events and mortality. It acts as a risk "amplifier" for the association between other risk factors and renal outcomes. [ABSTRACT FROM AUTHOR]

In the general population and in heart disease, pulmonary hypertension (PH) is a strong and independent risk factor for mortality and adverse cardiovascular outcomes. We performed a systematic review and meta‐analysis of longitudinal cohort studies of individuals with chronic kidney disease (CKD) of any‐stage (also including end‐stage kidney disease and kidney transplantation) stratified according to presence/absence of PH. Eighteen eligible studies (10 740 participants) were retrieved. PH had an overall pooled prevalence of 33% (95% CI 28–42) and portended a higher risk of all‐cause mortality (RR 2.08; 1.06–4.08), cardiovascular mortality (RR 3.77; 2.46–5.78) and non‐fatal cardiovascular events (RR 1.60; 1.28–1.99). PH is highly prevalent in CKD and end‐stage kidney disease and may represent a novel factor for mortality and cardiovascular risk stratification, particularly in selected sub‐categories. Future high‐quality research is required to confirm the need for clinical attention on PH in the CKD setting. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH), an acknowledged risk condition at the community level and in patients with heart or lung diseases, is now getting growing attention as a new, potentially modifiable cardiovascular (CV) risk factor also in individuals affected by kidney diseases. PH is highly prevalent in this setting, being about 3 to 6 times more frequent that in the general population and portends a risk excess for mortality, adverse CV outcomes and also worsen graft function in kidney transplant recipients. Several factors might be involved to explain PH in renal patients, including but not limited to volume overload, breath disorders, left heart dysfunction and the presence of highflow artero-venous fistulas. Targeting PH might lead to improved outcomes in renal patients but the lack of specific interventional studies and the need for more accurate evidence adopting standardized ways to assess PH leave the issue open for future research. [ABSTRACT FROM AUTHOR]

Background. It is the object of debate whether a low or high dialysate sodium concentration (DNa+) should be advocated in chronic haemodialysis patients. In this paper, we aimed at evaluating benefits and harms of different DNa+ prescriptions through a systematic review of the available literature. Methods. MEDLINE and CENTRAL databases were searched for studies comparing low or high DNa+ prescriptions. Outcomes of interest were mortality, blood pressure (BP), interdialytic weight gain (IDWG), plasma sodium, hospitalizations, use of anti-hypertensive agents and intradialytic complications. Results. Twenty-three studies (76 635 subjects) were reviewed. There was high heterogeneity in the number of patients analysed, overall study quality, duration of follow-up, DNa+ and even in the definition of 'high' or 'low' DNa+. The only three studies looking at mortality were observational. The risk of death was related to the plasma-DNa+ gradient, but was also shown to be confounded by indication from the dialysate sodium prescription itself. BP was not markedly affected by high or low DNa+. Patients treated with higher DNa+ had overall higher IDWG when compared with those with lower DNa+. Three studies reported a significant increase in intra-dialytic hypotensive episodes in patients receiving low DNa+. Data on hospitalizations and use of anti-hypertensive agents were sparse and inconclusive. Conclusions. There is currently no definite evidence proving the superiority of a low or high uniform DNa+ on hard or surrogate endpoints in maintenance haemodialysis patients. Future trials adequately powered to evaluate the impact of different DNa+ on mortality or other patient-centred outcomes are needed. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus is a frequent cause of the need for renal replacement therapy (RRT). Historically, RRT was started earlier in patients with diabetes, in an attempt to prevent complications of uraemia and diabetes. We did a systematic review to find support for this earlier start of dialysis in patients with versus without diabetes. Methods. The MEDLINE, EMBASE and CENTRAL databases were searched for articles about the timing of dialysis initiation in (subgroups of ) patients with diabetes and CKD Stage 5. Results. A total of 340 papers were screened and 11 papers were selected to be reviewed. Only three studies showed data of at least one subgroup of patients with diabetes. Two observational studies concluded that start of dialysis with a higher estimated glomerular filtration rate (eGFR) is beneficial with regard to survival, one did not find a difference and six observational studies concluded that start of dialysis with a lower eGFR is associated with better survival in patients with diabetes. The effect of timing of initiation of dialysis did not differ between patients with versus without diabetes. Lastly, one randomized controlled trial (two papers) reported that there was no difference in survival between start at higher versus lower eGFR overall and a P-value for the interaction with diabetes of P = 0.63, indicating no difference between patients with versus without diabetes with regard to the timing of start of dialysis and subsequent mortality on dialysis. Conclusions. There is no difference between early (eGFR) and late (lower eGFR) start of RRT with regard to mortality in patients with versus without diabetes. RRT should thus be initiated based on the same criteria in all patients, irrespective of the presence or absence of diabetes. [ABSTRACT FROM AUTHOR]

Background Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. Methods 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at baseline and after a follow-up period of 18 months. Ghrelin levels were significantly higher in cancer patients than in healthy subjects (573.31 ± 130 vs 320.20 ± 66.48 ng/ml, p < 0.0001), while obestatin (17.42 ± 7.12 vs 24.89 ± 5.54 ng/ml, p < 0.0001) and leptin (38.4 ± 21.2 vs 76.28 ± 17.48 ng/ml, p < 0.0001) values were lower. At ROC analyses the diagnostic profile of ghrelin (AUC 0.962; sensitivity 83%; specificity 98%), obestatin (AUC 0.798; sensitivity 74.5%; specificity 81.5%) and leptin (AUC 0.828; sensitivity 79%; specificity 73%) was superior to that of albumin (AUC 0.547; sensitivity 63%, specificity 69.4%) for detecting cachexia among cancer patients. On Cox multivariate analyses ghrelin (HR 1.02; 95% CI 1.01 - 1.03; p < 0.0001) and leptin (HR 0.94; 95% CI 0.92 - 0.96; p < 0.0001) were significant predictors of death even after correction for other known risk factors such as presence of metastasis and chronic kidney disease. Conclusion Ghrelin and leptin are promising biomarkers to diagnose cachexia and to predict survival in cancer patients. [ABSTRACT FROM AUTHOR]

Background/Aims: In this corollary analysis of the EXCITE study, we looked at possible differences in baseline risk factors and mortality between subjects excluded from the trial because non-eligible (n=216) or because eligible but refusing to participate (n=116). Methods: Baseline characteristics and mortality data were recorded. Survival and independent predictors of mortality were assessed by Kaplan-Meier and Cox regression analyses. Results: The incidence rate of mortality was higher in non-eligible vs. eligible non-randomized patients (21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced after adjustment for risk factors which differed in the two cohorts including age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides, cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to 2.35; P=0.017) and almost nullified after including in the same model also information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513). Conclusions: Deambulation ability mostly explains the difference in survival rate in non-eligible and eligible non-randomized patients in the EXCITE trial. Extending data analyses and outcome reporting also to subjects not taking part in a trial may be helpful to assess the representability of the study population. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]