Cardiovascular and non-cardiovascular mortality in dialysis patients: where is the link?
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ABSTRACT:
SUBMITTER: Jager KJ
PROVIDER: S-EPMC4089722 | biostudies-other | 2011 Jun
REPOSITORIES: biostudies-other
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Project description:Klotho is a membrane-bound protein acting as an obligatory coreceptor for fibroblast growth factor 23 (FGF23) in the kidney and parathyroid glands. The extracellular portion of its molecule may be cleaved and released into the blood and produces multiple endocrine effects. Klotho exerts anti-inflammatory and antioxidative activities that may explain its ageing suppression effects evidenced in mice; it also modulates mineral metabolism and FGF23 activities and limits their negative impact on cardiovascular system. Clinical studies have found that circulating Klotho is associated with myocardial hypertrophy, coronary artery disease and stroke and may also be involved in the pathogenesis of salt-sensitive hypertension with a mechanism sustained by inflammatory cytokines. As a consequence, patients maintaining high serum levels of Klotho not only show decreased cardiovascular mortality but also non-cardiovascular mortality. Klotho genetic polymorphisms may influence these clinical relationships and predict cardiovascular risk; rs9536314 was the polymorphism most frequently involved in these associations. These findings suggest that Klotho and its genetic polymorphisms may represent a bridge between inflammation, salt sensitivity, hypertension and mortality. This may be particularly relevant in patients with chronic kidney disease who have decreased Klotho levels in tissues and blood.
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Project description:Objectives:The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention. Methods:In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model. Results:Of 1753 patients, the mean age was 51.1 ± 14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29 ± 1.75. During the follow-up period of 31.2 ± 18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively (P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). After adjusting for confounding factors, the highest MLR tertile was significantly associated with a hazard ratio (HR) for CVD mortality of 1.45 (95% confidence interval, 1.13-2.51, P = 0.016). The Fine and Gray method analysis showed that using all-cause mortality as competing risk, the highest MLR tertile remained an independent predictor of CVD mortality (HR = 1.39, 95% CI 1.10-2.47, P = 0.021). Conclusions:Higher MLR levels at the commencement of PD may be independently associated with increased CVD mortality in PD patients.
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Project description:Introduction: Sclerostin has been reported to be a novel biomarker associated with the bone-vascular axis. In this study, we determined the relationships between serum sclerostin and all-cause mortality, the prevalence of cardiovascular events (CVEs), and coronary artery calcifications (CACs) in dialysis patients.Methods: A total of 165 dialysis patients (84 hemodialysis [HD] and 81 peritoneal dialysis [PD]) were enrolled in this study. We performed multivariable linear regression analysis to test the relationships between serum sclerostin levels and demographics and clinical parameters. We also performed Cox proportional hazard regression analysis to determine independent predictors of overall survival and CVEs.Results: The median serum sclerostin level was 250.9 pg/mL in dialysis patients. Kaplan-Meier analysis showed that both overall and CVE-free survival rates were significantly lower in the high serum sclerostin group (serum sclerostin level >250.9 pg/mL) compared to the low serum sclerostin group (serum sclerostin level ≤250.9 pg/mL) in patients with PD (p < 0.05). In patients with HD, only CVE-free survival rates notably declined in the high serum sclerostin group compared to the low serum sclerostin group (p = 0.029). However, serum sclerostin level was only an independent predictor of all-cause mortality and CVEs in patients with PD after adjusting for confounding factors (p < 0.05), and therefore was not an independent predictor for patients with HD (p > 0.05).Conclusions: A low serum sclerostin was associated with better overall survival and lower prevalence of CVEs in patients with PD, but had no relationships in patients with HD. We found that serum sclerostin level was not correlated with CACs in either patients with HD or PD.
| S-EPMC7170300 | biostudies-literature
Project description:The marked excess in cardiovascular mortality that results from uremia remains poorly understood.In 2 independent, nested case-control studies, we applied liquid chromatography-mass spectrometry-based metabolite profiling to plasma obtained from participants of a large cohort of incident hemodialysis patients. First, 100 individuals who died of a cardiovascular cause within 1 year of initiating hemodialysis (cases) were randomly selected along with 100 individuals who survived for at least 1 year (controls), matched for age, sex, and race. Four highly intercorrelated long-chain acylcarnitines achieved the significance threshold adjusted for multiple testing (P<0.0003). Oleoylcarnitine, the long-chain acylcarnitine with the strongest association with cardiovascular mortality in unadjusted analysis, remained associated with 1-year cardiovascular death after multivariable adjustment (odds ratio per SD 2.3 [95% confidence interval, 1.4 to 3.8]; P=0.001). The association between oleoylcarnitine and 1-year cardiovascular death was then replicated in an independent sample (n=300, odds ratio per SD 1.4 [95% confidence interval, 1.1 to 1.9]; P=0.008). Addition of oleoylcarnitine to clinical variables improved cardiovascular risk prediction using net reclassification (NRI, 0.38 [95% confidence interval, 0.20 to 0.56]; P<0.0001). In physiologic profiling studies, we demonstrate that the fold change in plasma acylcarnitine levels from the aorta to renal vein and from pre- to posthemodialysis samples exclude renal or dialytic clearance of long-chain acylcarnitines as confounders in our analysis.Our data highlight clinically meaningful alterations in acylcarnitine homeostasis at the time of dialysis initiation, which may represent an early marker, effector, or both of uremic cardiovascular risk.
| S-EPMC3886735 | biostudies-literature
Project description:Some variables including age, comorbidity of diabetes, and so on at dialysis initiation are associated with patient prognosis. Cardiovascular (CV) events are a major cause of death, and adequate models that predict prognosis in dialysis patients are warranted. Therefore, we created models using some variables at dialysis initiation. We used a database of 1,520 consecutive dialysis patients (median age, 70 years; 492 women [32.4%]) from a multicenter prospective cohort study. We established the primary endpoint as a composite of the incidence of first CV events or all-cause death. A multivariable Cox proportional hazard regression model was used to construct a model. We considered a complex and a simple model. We used area under the receiver operating characteristic curve (AUROC) to assess and compare the predictive performances of the prediction models and evaluated the improvement in discrimination using the complex model versus the simple model using net reclassification improvement (NRI). We then assessed integrated discrimination improvement (IDI) to evaluate improvements in average sensitivity and specificity. Of 392 deaths, 152 were CV-related. Totally, 506 CV events occurred during the follow-up period (median 1,285 days). Finally, 692 patients reached the primary endpoint. Baseline data were set at dialysis initiation. AUROC for the primary endpoint was 0.737 (95% confidence interval [CI], 0.712-0.761) in the simple model and 0.765 (95% CI, 0.741-0.788) in the complex model. There were significant intergroup differences in NRI (0.44; 95% CI, 0.34-0.53; p < 0.001) and IDI (0.02; 95% CI, 0.02-0.03; p < 0.001). We prepared a Shiny R application for each model to automatically calculate the predicted occurrence probability (https://statacademy.shinyapps.io/App_inaguma_20190717/). The complex model made more accurate predictions than the simple model. However, the intergroup difference was not significant. Hence, the simple model was more useful than the complex model. The tool was useful in a real-world clinical setting because it required only routinely available variables. Moreover, we emphasized that the tool could predict the incidence of CV events or all-cause mortality for individual patients. In the future, we must confirm its external validity in other prospective cohorts.
| S-EPMC6705850 | biostudies-literature
Project description:Cardiovascular mortality risk is high for peritoneal dialysis (PD) patients but it varies considerably among individuals. There is no clinical tool to predict cardiovascular mortality for PD patients yet. Therefore, we developed a cardiovascular mortality risk nomogram in a PD patient cohort. We derived and internally validated the nomogram in incident adult PD patients randomly assigned to a training (N = 918) or a validation (N = 460) dataset. The nomogram was built using the LASSO Cox regression model. Increasing age, history of cardiovascular disease or diabetes were consistent predictors of cardiovascular mortality. Low hemoglobin and serum albumin, high hypersensitive C-reactive protein and decreasing 24 hours urine output were identified as non-traditional cardiovascular risk predictors. In the validation dataset, the above nomogram performed good discrimination (1 year c-statistic = 0.83; 3 year c-statistic = 0.78) and calibration. This tool can classify patients between those at high risk of cardiovascular mortality (high-risk group) and those of low risk (low-risk group). Cardiovascular mortality was significantly different in the internal validation set of patients for the high-risk group compared to the low-risk group (HR 3.77, 2.14-6.64; p < 0.001). This novel nomogram can accurately predict cardiovascular mortality risk in incident PD patients.
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Project description:Background and Purpose. Cardiovascular disease is the major cause of death in dialysis patients. Although aldosterone antagonists were considered a treatment for severe heart failure patients to reduce cardiac mortality, whether treating patients undergoing maintenance dialysis with aldosterone antagonists could reduce the risk of cardiocerebrovascular (CCV) remains unclear. We aim to systematically assess the efficacy and tolerability of the addition of aldosterone antagonists to conventional therapy in patients undergoing maintenance dialysis. Materials and Methods. We searched PubMed, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database (CBM), and the China National Knowledge Infrastructure (CNKI) for relevant articles. The primary endpoint of interest was CCV mortality. The secondary endpoints were all-cause mortality, left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF). Publication bias was evaluated using funnel plots and Egger's test. The meta-analysis was performed using Review Manager software version 5.3. Results. This analysis included 10 randomized controlled trials (RCTs) with 1172 total chronic dialysis patients. The use of aldosterone antagonists in the dialysis population resulted in a marked reduction in CCV mortality (RR 0.42, 95% CI 0.26-0.65, P=0.0002) and all-cause mortality (RR0.46, 95%CI 0.32-0.66, P<0.0001). The LVEF was improved by treatment with aldosterone antagonists (WMD 6.35%, P<0.00001). Moreover, aldosterone antagonists decreased the LVMI (WMD -8.69 g/m2, P=0.0006), whereas aldosterone antagonists increased the occurrence of hyperkalemia (RR1.70, 95%CI 1-2.88, P=0.05) and gynecomastia (RR 8.01, 95% CI 2.44- 26.27, P=0.0006). Conclusions. Addition of aldosterone antagonists to conventional treatment in chronic dialysis patients may reduce CCV mortality, improve cardiac function, and simultaneously decrease LVMI.
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Project description:Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.
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Project description:Cigarette smoking is associated with increased cardiovascular morbidity and mortality in the general population, but the effect of smoking on these outcomes in the dialysis population is less well studied.Systematic review and meta-analysis of cohort studies.Adults treated with long-term hemodialysis or peritoneal dialysis. SELECTION CRITERIA FOR INCLUDED STUDIES: Cohort studies of unselected dialysis patients reporting the association between smoking status and cardiovascular morbidity and/or mortality.Smoking status (determined using patient report).(1) All-cause or cardiovascular mortality; (2) incident cardiovascular events.We identified 34 studies that fulfilled all inclusion criteria. Of these, 26 studies provided data for smoking and mortality and 10 (n = 6,538) were included in a meta-analysis. The pooled HR for all-cause mortality in smokers compared with nonsmokers was 1.65 (95% CI, 1.26-2.14; P < 0.001). 11 studies provided data for smoking and incident cardiovascular events; 5 (pooled n = 845) were included in a meta-analysis. The pooled HR for composite cardiovascular events in smokers compared with nonsmokers was 1.01 (95% CI, 0.98-1.05; P = 0.4).Data for these meta-analyses were heterogeneous. Few individual studies assessed smoking as the primary variable of interest.Active smoking is associated with a significant increase in all-cause mortality in dialysis patients, although there was no corresponding increased risk of cardiovascular events.
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Project description:This review article focuses on the most significant cardiovascular complications in dialysis patients [sudden cardiac death (SCD), acute coronary syndromes, heart failure, and atrial fibrillation].Current and ongoing research aims to quantify the rate and pattern of significant arrhythmia in dialysis patients and to determine the predominant mechanism of SCD. Preliminary findings from these studies suggest a high rate of atrial fibrillation and that bradycardia and asystole may be more frequent than ventricular arrhythmia as a cause of sudden death. A recently published matched cohort study in dialysis patients who received a defibrillator for primary prevention showed that there was no significant difference in mortality rates between defibrillator-treated patients and propensity-matched controls. Two randomized controlled trials are currently recruiting participants and will hopefully answer the question of whether implantable or wearable cardioverter defibrillators can prevent SCD. An observational study using United States Renal Data System data demonstrated how difficult it is to keep hemodialysis patients on warfarin, as more than two-thirds discontinued the drug during the first year. The ISCHEMIA-CKD trial may provide answers about the optimal strategy for the treatment of atherosclerotic coronary disease in patients with advanced chronic kidney disease.The article reviews the diagnosis of acute coronary syndromes in dialysis patients, current literature on myocardial revascularization, and data on fatal and nonfatal cardiac arrhythmia. The new classification of heart failure in end-stage renal disease is reviewed. Finally, available cohort studies on warfarin for stroke prevention in dialysis patients with atrial fibrillation are reviewed.
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