Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients.

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Value of bioimpedance analysis estimated "dry weight" in maintenance dialysis patients: a systematic review and meta-analysis.

BACKGROUND: Volume overload is a common complication in patients with end-stage kidney disease who undergo maintenance dialysis therapy and associated with hypertension, left ventricular hypertrophy and mortality in this population. Although bioimpedance analysis (BIA), an objective method to assess overhydration, is associated with poor outcomes in observational studies, in randomized controlled trials (RCTs) the results were conflicting. We have examined the role of BIA for assessing the "dry weight" and fluid status in order to improve fluid overload in comparison with a control or clinical-based prescription in patients with ESKD receiving haemodialysis or peritoneal dialysis. METHODS: All RCTs and quasi-RCTs in which BIA was used to improve fluid overload and assess the effect on all-cause mortality, cardiovascular morbidity, systolic blood pressure and volume control and arterial stiffness were included. RESULTS: Seven RCTs with 1312 patients could be included in this review. In low-to-medium quality of the evidence, the use of BIA did not reduce all-cause mortality (relative risk 0.87, 95% CI 0.54-1.39) and had small to no effect on body change, but it improved systolic blood pressure control (mean difference (MD) -2.73 mmHg, 95% CI -5.00 to -0.46 mmHg) and reduce overhydration, as measured by BIA, with 0.43 L [(MD), 95% CI 0.71-0.15 L]. CONCLUSION: In ESKD patients, BIA-based interventions for correction of overhydration have little to no effect on all-cause mortality, whereas BIA improved systolic blood pressure control. Our results should be interpreted with caution as the size and power of the included studies are low. Further studies, larger or with a longer follow-up period, should be performed to better describe the effect of BIA-based strategies on survival.

Addition of silymarin to renin-angiotensin system blockers in normotensive patients with type 2 diabetes mellitus and proteinuria: a prospective randomized trial.

BACKGROUND: In the last decade, despite constant investigation, no current single treatment has been able to decrease the incidence of diabetic nephropathy and to significantly reduce progression of diabetic CKD. METHODS: Patients with type 2 diabetes mellitus and proteinuria (>0.5 g/day) after a screening and treatment optimization phase were randomly assigned to receive silymarin or placebo. The primary outcome was a composite outcome: mortality, decline of eGFR > 50% and renal replacement therapy. Secondary outcomes were a composite renal outcome (defined as a decline of eGFR ≥ 50% or ESRD) and also to test the effect of silymarin on the change in eGFR and proteinuria. We also assessed the adverse effects (hospitalizations, headache or gastrointestinal symptoms) during the study. RESULTS: One hundred and two patients were included in the study. There were no significant differences between the two study groups regarding the primary and renal outcomes (HR 0.62, 95% CI 0.3-1.2, p = 0.15; HR 0.56, 95% CI 0.26-1.24, p = 0.16, respectively). At study end, eGFR declined significantly in both arms (p < 0.001), irrespective of the treatment group allocation, and there were no significant changes in proteinuria. There was a significant difference in hospitalizations rates between the two study groups (0.61, 95% CI 0.44-0.85). CONCLUSIONS: Silymarin did not show a significant reduction in the primary and secondary outcomes. Importantly, silymarin treatment was associated with a significant reduction in the hospitalization rate.

Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Type 2 diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease and nephropathy-now the leading cause of end-stage renal disease and dialysis in Europe and the United States. Inflammation and oxidative stress play a pivotal role in the development of diabetic complications. Silymarin, an herbal drug with antioxidant and anti-inflammatory properties, may improve glycemic control and prevent the progression of the complications. In a systematic review and meta-analysis including five randomized controlled trials and 270 patients, routine silymarin administration determines a significant reduction in fasting blood glucose levels (-26.86 mg/dL; 95% CI -35.42-18.30) and HbA1c levels (-1.07; 95% CI -1.73-0.40) and has no effect on lipid profile. Benefits for silymarin on proteinuria and CKD progressions are reported in only one small study and are uncertain. However, being aware of the low quality of the available evidence and elevated heterogeneity of these studies, no recommendation can be made and further studies are needed.

Bioimpedance analysis versus lung ultrasonography for optimal risk prediction in hemodialysis patients.

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. Two bedside methods are increasingly utilized to evaluate objectively fluid status-bioimpedance and lung ultrasonography, but there is no available direct, head-to-head comparison of their prognostic significance. Importantly, their predictive abilities have never been tested in a HD population, alongside those of a classic model that also incorporates established echocardiographic parameters of increased mortality risk. Between 26 May 2011 and 26 October 2012, we included in the study 173 patients undergoing chronic HD treatment for at least 3 months in a single dialysis unit. Relative fluid overload (RFO) and B-lines score (BLS) were used as candidate predictors. From Cox survival analysis we evaluated the increase in the predictive abilities for all-cause mortality of adding continuous RFO or BLS to a model including conventional predictors . 31 patients (17.9 %) died during a median follow-up of 21.3 (interquartile range 19.9-30.3) months. All Cox models showed good calibration. The C statistic for the all-cause mortality prediction increased significantly when the RFO was included into the baseline model (ΔC statistics 0.058 95 %CI = 0.003-0.114), but not when the BLS was included into the baseline model. Only the model that incorporated RFO showed significantly better risk reclassification abilities than the baseline model (IDI = 3.6 % and continuous NRI = 24.8 %). Fluid overload, as assessed by bioimpedance, and not by lung ultrasonography, improves risk prediction for death, beyond classical and echocardiographic-based risk prediction scores/parameters.

Electrocardiogram abnormalities and heart rate variability in predicting mortality and cardiovascular events among hemodialyzed patients.

PURPOSE: The aim of the study was to evaluate the correlation between electrocardiographic parameters and heart rate variability with cardiovascular events and mortality among chronic hemodialysis patients. METHODS: In this prospective study, we enrolled 116 asymptomatic patients in whom we performed ambulatory 24-h electrocardiographic Holter monitoring and before and after hemodialysis electrocardiographs. We measured the interval (PR, QRS, QTc, QTc dispersion) differences on the surface electrocardiographs and obtained frequency-domain measures from Holter monitoring (VLF, LF, HF and the LF/HF ratio). RESULTS: During the follow-up period, 13 participants died (11.2 %) and 16 (13.8 %) patients experienced a cardiovascular event. The pre-post-dialysis difference in QTc interval was the best predictor for cardiovascular events (95 % CI 0.453-0.786), while pre-dialysis QRS interval was the predictor for all-cause mortality (95 % CI 1.134-3.136). Also, both outcomes were predicted by pre-post-dialysis difference in PR interval and VLF. CONCLUSIONS: Interval changes during hemodialysis are predictive for cardiovascular events and mortality. Autonomic dysfunction and changes in PR should be monitored routinely, particularly in patients with suspected coronary artery disease.

Erythropoiesis-stimulating agents (ESA) for preventing the progression of chronic kidney disease: a meta-analysis of 19 studies.

BACKGROUND: The effect of anemia correction on kidney function in chronic kidney disease (CKD) patients remains unclear. As 19-40% of patients with CKD receive an erythropoiesis-stimulating agent (ESA), this is a potentially important consideration. SUMMARY: We conducted a systematic review and meta-analysis of randomized trials to January 1, 2014 in adult patients with CKD stages 1 to 4. SELECTION CRITERIA FOR STUDIES: randomized controlled trials of at least 2 months duration. Patients were allocated to ESA versus placebo, no treatment, or different ESA doses with the purpose of achieving a higher versus a lower hemoglobin target. The analyzed outcomes were the need for renal replacement therapy, doubling of serum creatinine, change in GFR (ml/min), mortality and withdrawal of treatment due to adverse events. A total of 19 trials (n = 8,129 participants with CKD stage 1-4) were reviewed. There was no difference in the risk of end-stage kidney disease (RR, 0.97 [CI 0.83-1.20], 17 trials, 8,104 participants), change in GFR (Mean Difference [MD] -0.45 [-2.21, 1.31], 9 trials, 1,848 participants) or withdrawal of treatment due to adverse events (RR, 1.18 [CI 0.77-1.81], 10 trials, n = 1,958 participants) for patients at higher hemoglobin (Hb) targets. Furthermore, no statistically significant differences in mortality (Risk Ratio [RR] 1.10 [CI 0.90-1.35], 16 trials, n = 8,082 participants) were observed. Key Messages: There is no evidence that ESA treatment affects renal function in patients with CKD. Use of these agents should not therefore be influenced by considerations about influencing CKD progression.

Procalcitonin: diagnostic value in systemic infections in chronic kidney disease or renal transplant patients.

PURPOSE: Although procalcitonin (PCT) has been described as a marker of infection and inflammation, it has not been extensively studied in patients with chronic kidney disease (CKD), end stage renal disease, or renal transplant. METHODS: PCT was routinely tested in 82 (56 dialyzed patients and 28 renal transplant recipients) consecutive cases with a strong clinical suspicion of infection, during a 6-month period, in a single referral unit. RESULTS: During the study period, 58/82 cases had confirmed infections as per definition. Patients with confirmed infections had higher values for PCT [median = 2.5 ng/mL, interquartile range (IR) = 0.9-5 ng/mL] than those without (median = 0.3 ng/mL, IR = 0.1-0.5 ng/mL), p < 0.001. Overall, for a cutoff value of 0.5 ng/mL, the sensitivity of the test was 93.1 % and the specificity 78.6. CONCLUSION: Our data indicate that significantly elevated PCT concentrations offer good sensitivity and specificity for the early diagnosis of systemic bacterial infection in patients with CKD.

A cross-sectional study regarding the impact of end-stage renal disease on quality of life.

UNLABELLED: The number and severity of physical and psychological symptoms reported by chronic hemodialysis (HD) patients are significant and increasing; with a clear need to clarify which symptom intervention is the most needed. Measurements of quality of life (QoL) have shown, for many decades, an impairment of both physical and psychological aspects in both chronic kidney disease (CKD) pre-dialysis and in end stage renal disease (ESRD) patients. This cross-sectional study was conducted assess the quality of life of a Romanian hemodialysis population and the impact of several clinical and biochemical factors. MATERIAL AND METHODS: A total of 102 patients (41 males, 61 females) with a mean age of 52.5 +/- 12.0 years, who were treated with HD three times per week in our dialysis center were included in the study. All subjects completed the Short Form Health Survey Questionnaire (SF-36). Clinical and biochemical parameters were extracted from the EUCLID electronic database. RESULTS: Our measurement showed a deteriorated QoL in our population, all of the included subjects presenting with much lower scores in both physical and mental components than the reference values of SF-36. We did not found any statistic significant correlation between hemoglobin (Hgb) levels or dialysis adequacy and different domains of the SF-36. The only significant association was found between age and the physical component of the SF-36, implying that older patients perceive a more degraded quality of life. CONCLUSION: HD patients experience a great burden from physical and psychological symptoms of the disease, perceiving an important impairment in their quality of life, especially regarding the physical component.