Baseline serum interleukin-6 predicts cardiovascular events in incident peritoneal dialysis patients.
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ABSTRACT:
SUBMITTER: Cho Y
PROVIDER: S-EPMC4335926 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Repeated exposure to peritoneal dialysis (PD) solutions contributes to cumulative intraperitoneal inflammation and peritoneal injury. The present study aimed to explore the capacity of dialysate interleukin-6(IL-6) to a) predict peritoneal membrane function and peritonitis in incident PD patients, and b) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on dialysate IL-6 levels. METHODS: The study included 88 incident participants from the balANZ trial who had completed 24-months of follow-up. Change in peritoneal solute transport rate (PSTR) and peritonitis were primary outcome measures, and the utility of IL-6 and IL-6 appearance rate (IL-6 AR) in predicting these outcomes was analyzed using multilevel linear regression and Cox proportional hazards models, respectively. Sensitivity analyses were performed by analyzing outcomes in a peritonitis-free cohort (n = 56). RESULTS: Dialysate IL-6 concentration significantly increased from baseline to 24 months (mean difference 19.07 pg/mL; P < 0.001) but was not affected by the type of PD solution received (P = 0.68). An increase in PSTR from baseline was associated with higher levels of IL-6 (P = 0.004), the use of standard solutions (P = 0.005) and longer PD duration (P < 0.001). Baseline IL-6 level was not associated with a shorter time to first peritonitis (adjusted hazard ratio 1.00, 95% CI 0.99-1.00, P = 0.74). Analysis of IL-6 AR as well as sensitivity analyses in a peritonitis-free cohort yielded comparable results. CONCLUSION: Dialysate IL-6 concentration increased with longer PD duration and was a significant, independent predictor of PSTR. The use of biocompatible PD solutions exerted no significant effect on dialysate IL-6 levels but did abrogate the increase in PSTR associated with standard PD solutions. This is the first study to examine the impact of biocompatible solutions on the utility of IL-6 in predicting PSTR and peritonitis.
| S-EPMC3893539 | biostudies-literature
Project description:BackgroundFluid overload is common among asymptomatic peritoneal dialysis (PD) patients. We aim to determine the prevalence and prognostic significance of fluid overload, as measured by bioimpedance spectroscopy, in asymptomatic incident PD patients.MethodsWe performed a single-center study on 311 incident PD patients. Volume status was represented by the volume of overhydration (OH), OH/extracellular water (ECW) ratio, ECW/total body water (TBW) ratio, and ECW to intracellular water (ICW) ratio (E:I ratio). Patient survival, technique survival and cardiovascular event-free survival were determined.ResultsThe median period of follow up was 27.3 months. Fluid overload was present in 272 patients (87.5%) when defined as OH volume over 1.1L. All hydration parameters significantly correlated with Charlson Comorbidity Index, and inversely with total Kt/V, and serum albumin. Multivariate cause-specific Cox analysis showed that volume status independently predicted patient survival; every 0.1 unit increase in E:I ratio was associated with 24.5% increase in all-cause mortality (adjusted cause-specific hazard ratio [ACSHR] 1.245, p = 0.002). Hydration status was also an independent predictor of cardiovascular event-free survival after excluding hospital admission for congestive heart failure; each 0.1 unit increase in E:I ratio was associated with 18.7% decrease in cardiovascular event-free survival (ACSHR 1.187, p = 0.011). In contrast, hydration parameters were not associated with technique survival.ConclusionsFluid overload is common in asymptomatic incident PD patients and is a strong predictor of patient survival and cardiovascular event. The impact of bioimpedance spectroscopy-guided fluid management on the outcome of PD patients deserves further study.
| S-EPMC6089451 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES: The single-nucleotide polymorphism (SNP) -717A→G substitution, rs2794521, was found in the promoter of the C-reactive protein (CRP) gene. Functional studies showed that A allele promoter has higher transcriptional activity than the G allele. This study investigated the association between this SNP and the outcome of Chinese patients undergoing peritoneal dialysis (PD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study included 441 new PD patients (232 men; mean age ± SD, 56.7±13.5 years). CRP genotyping was determined; patients were followed for 41.3±18.3 months for cardiovascular events. RESULTS: For the entire cohort, 5-year event-free survival rates did not differ between the AA and AG/GG groups (35.7% and 31.9%, respectively; P=0.64). However, there was significant interaction between plasma cholesterol levels and CRP genotype groups on event-free survival (P=0.04 for interaction). For patients with cholesterol levels of 200 mg/dl or greater, the 5-year event-free survival rate in the AG/GG group was significantly better than that in the AA group (54.7% versus 40.0%; P=0.04), whereas there was no difference in event-free survival between genotype groups for patients with cholesterol levels less than 200 mg/dl. CONCLUSIONS: CRP gene -717AG or GG genotypes is associated with cardiovascular benefit to Chinese PD patients with cholesterol levels of 200 mg/dl or greater. These findings suggest a complex interaction among cholesterol, CRP, and cardiovascular disease in PD patients.
| S-EPMC3280019 | biostudies-other
Project description:BackgroundNon-euvolaemia in peritoneal dialysis (PD) patients is associated with elevated mortality risk. There is an urgent need to collect data to help us understand the association between clinical practices and hydration and nutritional status, and their effects on patient outcome.MethodsThe aim of this prospective international, longitudinal observational cohort study is to follow up the hydration and nutritional status, as measured by bioimpedance spectroscopy using the body composition monitor (BCM) of incident PD patients for up to 5 years. Measures of hydration and nutritional status and of clinical, biochemical and therapy-related data are collected directly before start of PD treatment, at 1 and 3 months, and then every 3 months. This paper presents the protocol and a pre-specified analysis of baseline data of the cohort.ResultsA total of 1092 patients (58.1% male, 58.0 ± 15.3 years) from 135 centres in 32 countries were included. Median fluid overload (FO) was 2.0 L (males) and 0.9 L (females). Less than half of the patients were normohydrated (38.7%), whereas FO > 1.1 L was seen in 56.5%. Systolic and diastolic blood pressure were 139.5 ± 21.8 and 80.0 ± 12.8 mmHg, respectively, and 25.1% of patients had congestive heart failure [New York Heart Association (NYHA) 1 or higher]. A substantial number of patients judged to be not overhydrated on clinical judgement appeared to be overhydrated by BCM measurement. Overhydration at baseline was independently associated with male gender and diabetic status.ConclusionsThe majority of patients starting on PD are overhydrated already at start of PD. This may have important consequences on clinical outcomes and preservation of residual renal function. Substantial reclassification of hydration status by BCM versus on a clinical basis was necessary, especially in patients who were not overtly overhydrated. Both clinical appreciation and bioimpedance should be combined in clinical decision-making on hydration status.
| S-EPMC4425480 | 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.
| S-EPMC5654762 | 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:BACKGROUND:Abnormalities in serum potassium are risk factors for sudden cardiac death and arrhythmias among dialysis patients. Although a previous study in hemodialysis patients has shown that race/ethnicity may impact the relationship between serum potassium and mortality, the relationship remains unclear among peritoneal dialysis (PD) patients where the dynamics of serum potassium is more stable. METHODS:Among 17,664 patients who started PD between January 1, 2007 and December 31, 2011 in a large US dialysis organization, we evaluated the association of serum potassium levels with all-cause and arrhythmia-related deaths across race/ethnicity using time-dependent Cox models with adjustments for demographics. We also used restricted cubic spline functions for serum potassium levels to explore non-linear associations. RESULTS:Baseline serum potassium levels were the highest among Hispanics (4.2 ± 0.7 mEq/L) and lowest among non-Hispanic blacks (4.0 ± 0.7 mEq/L). Among 2,949 deaths during the follow-up of median 2.2 (interquartile ranges 1.3-3.2) years, 683 (23%) were arrhythmia-related deaths. Overall, both hyperkalemia and hypokalemia (i.e., serum potassium levels >5.0 and <3.5 mEq/L, respectively) were associated with higher all-cause and arrhythmia-related mortality. In a stratified analysis according to race/ethnicity, the association of hypokalemia with all-cause and arrhythmia-related mortality was consistent with an attenuation for arrhythmia-related mortality in non-Hispanic blacks. Hyperkalemia was associated with all-cause and arrhythmia-related mortality in non-Hispanic whites and non-Hispanic blacks, but no association was observed in Hispanics. CONCLUSION:Among incident PD patients, hypokalemia was consistently associated with all-cause and arrhythmia-related deaths irrespective of race/ethnicity. However, while hyperkalemia was associated with both death outcomes in non-Hispanic blacks and whites, it was not associated with either death outcome in Hispanic patients. Further studies are needed to demonstrate whether different strategies should be followed for the management of serum potassium levels according to race/ethnicity.
| S-EPMC6856395 | biostudies-literature
Project description:Prior studies have shown the association of low serum magnesium levels with adverse health outcomes in patients undergoing hemodialysis. There is a paucity of such studies in patients undergoing peritoneal dialysis (PD).Cohort study.10,692 patients treated with PD from January 1, 2007, through December 31, 2011, in facilities operated by a single large dialysis organization in the United States.Baseline serum magnesium levels, examined as 5 categories (<1.8, 1.8-<2.0, 2.0-<2.2 [reference], 2.2-<2.4, and ?2.4mg/dL).Time to first hospitalization and time to death using competing-risks regression models.The distribution of baseline serum magnesium levels in the cohort was <1.8mg/dL, 1,928 (18%); 1.8 to <2.0mg/dL, 2,204 (21%); 2.0 to <2.2mg/dL, 2,765 (26%); 2.2 to <2.4mg/dL, 1,765 (16%); and ?2.4mg/dL, 2,030 (19%). Of 10,692 patients, 6,465 (60%) were hospitalized at least once and 1,392 (13%) died during follow-up (median, 13; IQR, 7-23 months). Baseline serum magnesium level < 1.8mg/dL was associated with higher risk for hospitalization and all-cause mortality after adjustment for demographic and clinical characteristics (adjusted HRs of 1.23 [95% CI, 1.14-1.33] and 1.21 [95% CI, 1.03-1.42], respectively). The higher risk for hospitalization persisted upon adjustment for laboratory variables, whereas that for all-cause mortality was attenuated to a nonsignificant level. The greatest risk for hospitalization was in patients with low serum albumin levels (<3.5g/dL; P for interaction < 0.001).Possibility of residual confounding by unmeasured variables cannot be excluded.Lower serum magnesium levels may be associated with higher risk for hospitalization in incident PD patients, particularly those with hypoalbuminemia. Additional studies are needed to confirm these findings and investigate whether correction of hypomagnesemia reduces these risks.
| S-EPMC5035573 | biostudies-literature
Project description:BackgroundIrisin is a recently discovered myokine thought to be involved in multiple metabolism abnormalities in most dialysis patients. However, the myokine has not been thoroughly studied in peritoneal dialysis. This study aimed to evaluate serum irisin levels and establish their relation to dialysis adequacy, insulin resistance, and bone metabolism status in patients on peritoneal dialysis.MethodsA total of 59 nondiabetic prevalent peritoneal dialysis patients and 52 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentration was assessed by enzyme-linked immunosorbent assay. The correlations between serum irisin and dialysis adequacy, clinical, and metabolic variables were investigated.ResultsSerum irisin levels were lower in nondiabetic peritoneal dialysis patients (17.02ng/ml) compared with healthy controls (22.17ng/ml, P<0.001). Multivariate regression analysis revealed that fasting glucose levels were correlated inversely with serum irisin levels in peritoneal dialysis patients. Serum irisin levels were associated with neither insulin resistance nor bone metabolism in our patients. Serum irisin levels were positively associated with peritoneal Kt/Vurea (β = 4.933, 95% confidence interval [CI] = 0.536-9.331, P = 0.029) and peritoneal CCr (β = 0.259, 95% CI = 0.053-0.465, P = 0.015) among peritoneal dialysis patients.ConclusionsThe study demonstrated that non-diabetic peritoneal dialysis patients have lower serum irisin levels, and the levels were correlated with peritoneal dialysis adequacy, indicating adequate dialysis may improve irisin secretion. Additional studies are needed to provide a confirmation.
| S-EPMC5406024 | biostudies-literature