Dataset Information

Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD.

ABSTRACT:

Introduction

Patients with end-stage renal disease (ESRD) experience disproportionately high cardiovascular morbidity and mortality. Accumulating evidence suggests a role for the circulating microbiome in the pathogenesis of cardiovascular disease; however, little is known about its association with premature cardiovascular mortality in ESRD.

Methods

In a pilot case-control study of 17 hemodialysis patients who died of a cardiovascular event and 17 matched hemodialysis controls who remained alive during a median follow-up of 2.0 years, we compared the levels and composition of circulating microbiome, including Bacteria, Archaea, and Fungi, in serum samples by quantitative polymerase chain reaction and 16S or Internal Transcribed Spacer (ITS) ribosomal RNA (rRNA) sequencing, respectively. Associations of the circulating cell-free microbial signatures with clinical parameters and cardiovascular death were examined using the Spearman rank correlation and multivariable conditional logistic regression, respectively.

Results

Both 16S and ITS rRNA were detectable in all (except 3 for ITS) examined patients' serum samples. Despite no significant difference in 16S rRNA levels and α diversity between cases and controls, taxonomic analysis demonstrated differential community membership between groups, with significantly greater Actinobacteria and less Proteobacteria observed in cases than in controls at the phylum level. Proportions of Actinobacteria and Proteobacteria phyla were significantly correlated with plasma nuclear factor erythroid 2-related factor 2 (Nrf2) levels (rho = -0.41 and 0.42, P = 0.015 and 0.013, respectively) and marginally associated with risk of cardiovascular death (adjusted odds ratios [95% confidence intervals] = 1.12 [0.98-1.29] and 0.88 [0.76-1.02] for 1% increase, respectively).

Conclusion

Alterations of the circulating cell-free microbial signatures may be associated with higher premature cardiovascular mortality in ESRD.

SUBMITTER: Sumida K

PROVIDER: S-EPMC8484116 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD.

Sumida Keiichi K Pierre Joseph F JF Han Zhongji Z Mims Tahliyah S TS Potukuchi Praveen Kumar PK Yuzefpolskaya Melana M Colombo Paolo C PC Demmer Ryan T RT Datta Susmita S Kovesdy Csaba P CP

Kidney international reports 20210804 10

<h4>Introduction</h4>Patients with end-stage renal disease (ESRD) experience disproportionately high cardiovascular morbidity and mortality. Accumulating evidence suggests a role for the circulating microbiome in the pathogenesis of cardiovascular disease; however, little is known about its association with premature cardiovascular mortality in ESRD.<h4>Methods</h4>In a pilot case-control study of 17 hemodialysis patients who died of a cardiovascular event and 17 matched hemodialysis controls wh ...[more]

PMID: 34622101

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Project description:IntroductionPatients with kidney failure with replacement therapy (KFRT) suffer from a disproportionately high cardiovascular disease burden. Circulating small non-coding RNAs (c-sncRNAs) have emerged as novel epigenetic regulators and are suggested as novel biomarkers and therapeutic targets for cardiovascular disease; however, little is known about the associations of c-sncRNAs with premature cardiovascular death in KFRT.MethodsIn a pilot case-control study of 50 hemodialysis patients who died of cardiovascular events as cases, and 50 matched hemodialysis controls who remained alive during a median follow-up of 2.0 years, we performed c-sncRNAs profiles using next-generation sequencing to identify differentially expressed circulating microRNAs (c-miRNAs) between the plasma of cases and that of controls. mRNA target prediction and pathway enrichment analysis were performed to examine the functional relevance of differentially expressed c-miRNAs to cardiovascular pathophysiology. The association of differentially expressed c-miRNAs with cardiovascular mortality was examined using multivariable conditional logistic regression.ResultsThe patient characteristics were similar between cases and controls, with a mean age of 63 years, 48% male, and 54% African American in both groups. We detected a total of 613 miRNAs in the plasma, among which five miRNAs (i.e., miR-129-1-5p, miR-500b-3p, miR-125b-1-3p, miR-3648-2-5p, and miR-3150b-3p) were identified to be differentially expressed between cases and controls with cut-offs of p < 0.05 and log2 fold-change (log2FC) > 1. When using more stringent cut-offs of p-adjusted < 0.05 and log2FC > 1, only miR-129-1-5p remained significantly differentially expressed, with higher levels of miR-129-1-5p in the cases than in the controls. The pathway enrichment analysis using predicted miR-129-1-5p mRNA targets demonstrated enrichment in adrenergic signaling in cardiomyocytes, arrhythmogenic right ventricular cardiomyopathy, and oxytocin signaling pathways. In parallel, the circulating miR-129-1-5p levels were significantly associated with the risk of cardiovascular death (adjusted OR [95% CI], 1.68 [1.01-2.81] for one increase in log-transformed miR-129-1-5p counts), independent of potential confounders.ConclusionsCirculating miR-129-1-5p may serve as a novel biomarker for premature cardiovascular death in KFRT.

Project description:BackgroundSerum bicarbonate or total carbon dioxide (CO2) concentrations decline as chronic kidney disease (CKD) progresses and rise after dialysis initiation. While metabolic acidosis accelerates the progression of CKD and is associated with higher mortality among patients with end stage renal disease (ESRD), there are scarce data on the association of CO2 concentrations before ESRD transition with post-ESRD mortality.MethodsA historical cohort from the Transition of Care in CKD (TC-CKD) study includes 85,505 veterans who transitioned to ESRD from October 1, 2007, through March 31, 2014. After 1,958 patients without follow-up data, 3 patients with missing date of birth, and 50,889 patients without CO2 6 months prior to ESRD transition were excluded, the study population includes 32,655 patients. Associations between CO2 concentrations averaged over the last 6 months and its rate of decline during the 12 months prior to ESRD transition and post-ESRD all-cause, cardiovascular (CV), and non-CV mortality were examined by using hierarchical adjustment with Cox regression models.ResultsThe cohort was on average 68 ± 11 years old and included 29% Black veterans. Baseline concentrations of CO2 were 23 ± 4 mEq/L, and median (interquartile range) change in CO2 were -1.8 [-3.4, -0.2] mEq/L/year. High (≥28 mEq/L) and low (<18 mEq/L) CO2 concentrations showed higher adjusted mortality risk while there was no clear trend in the middle range. Consistent associations were observed irrespective of sodium bicarbonate use. There was also a U-shaped association between the change in CO2 and all-cause, CV, and non-CV mortality with the lowest risk approximately at -2.0 and 0.0 mEq/L/year among sodium bicarbonate nonusers and users, respectively, and the highest mortality was among patients with decline in CO2 >4 mEq/L/year.ConclusionBoth high and low pre-ESRD CO2 levels (≥28 and <18 mEq/L) during 6 months prior to dialysis transition and rate of CO2 decline >4 mEq/L/year during 1 year before dialysis initiation were associated with greater post-ESRD all-cause, CV, and non-CV mortality. Further studies are needed to determine the optimal management of CO2 in patients with advanced CKD stages transitioning to ESRD.

Dataset Information

Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD.

Introduction

Methods

Results

Conclusion

Publications

Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD.

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