Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD

Keiichi Sumida; Joseph F. Pierre; Zhongji Han; Tahliyah S. Mims; Praveen Kumar Potukuchi; Melana Yuzefpolskaya; Paolo C. Colombo; Ryan T. Demmer; Susmita Datta; Csaba P. Kovesdy

doi:10.1016/j.ekir.2021.07.023

Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD

Keiichi Sumida, Joseph F. Pierre, Zhongji Han, Tahliyah S. Mims, Praveen Kumar Potukuchi, Melana Yuzefpolskaya, Paolo C. Colombo, Ryan T. Demmer, Susmita Datta, Csaba P. Kovesdy

Epidemiology & Community Health

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2617-2628
Number of pages	12
Journal	Kidney International Reports
Volume	6
Issue number	10
DOIs	https://doi.org/10.1016/j.ekir.2021.07.023
State	Published - Oct 1 2021

Bibliographical note

Funding Information:
We would like to thank Dr. Amandeep Bajwa (Department of Surgery, School of Medicine, University of Tennessee Health Science Center) for assistance in DNA extraction. Research reported in this publication was supported by National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (NIH) under award number R01DK125586 to KS. JFP is funded by the NIH under award numbers R01CA253329 and R01DK125047 . CPK is an employee of the US Department of Veterans affairs. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the Department of Veterans Affairs or the US government. The results of this paper have not been published previously in whole or part.

Funding Information:
We would like to thank Dr. Amandeep Bajwa (Department of Surgery, School of Medicine, University of Tennessee Health Science Center) for assistance in DNA extraction. Research reported in this publication was supported by National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (NIH) under award number R01DK125586 to KS. JFP is funded by the NIH under award numbers R01CA253329 and R01DK125047. CPK is an employee of the US Department of Veterans affairs. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the Department of Veterans Affairs or the US government. The results of this paper have not been published previously in whole or part.

Publisher Copyright:
© 2021 International Society of Nephrology

Keywords

cardiovascular disease
chronic kidney disease
circulating microbiome
end-stage renal disease
inflammation
mortality

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Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ekir.2021.07.023

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title = "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{\textquoteright} 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.",

keywords = "cardiovascular disease, chronic kidney disease, circulating microbiome, end-stage renal disease, inflammation, mortality",

author = "Keiichi Sumida and Pierre, {Joseph F.} and Zhongji Han and Mims, {Tahliyah S.} and Potukuchi, {Praveen Kumar} and Melana Yuzefpolskaya and Colombo, {Paolo C.} and Demmer, {Ryan T.} and Susmita Datta and Kovesdy, {Csaba P.}",

note = "Funding Information: We would like to thank Dr. Amandeep Bajwa (Department of Surgery, School of Medicine, University of Tennessee Health Science Center) for assistance in DNA extraction. Research reported in this publication was supported by National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (NIH) under award number R01DK125586 to KS. JFP is funded by the NIH under award numbers R01CA253329 and R01DK125047 . CPK is an employee of the US Department of Veterans affairs. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the Department of Veterans Affairs or the US government. The results of this paper have not been published previously in whole or part. Funding Information: We would like to thank Dr. Amandeep Bajwa (Department of Surgery, School of Medicine, University of Tennessee Health Science Center) for assistance in DNA extraction. Research reported in this publication was supported by National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (NIH) under award number R01DK125586 to KS. JFP is funded by the NIH under award numbers R01CA253329 and R01DK125047. CPK is an employee of the US Department of Veterans affairs. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the Department of Veterans Affairs or the US government. The results of this paper have not been published previously in whole or part. Publisher Copyright: {\textcopyright} 2021 International Society of Nephrology",

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doi = "10.1016/j.ekir.2021.07.023",

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T1 - Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD

AU - Sumida, Keiichi

AU - Pierre, Joseph F.

AU - Han, Zhongji

AU - Mims, Tahliyah S.

AU - Potukuchi, Praveen Kumar

AU - Yuzefpolskaya, Melana

AU - Colombo, Paolo C.

AU - Demmer, Ryan T.

AU - Datta, Susmita

AU - Kovesdy, Csaba P.

N1 - Funding Information: We would like to thank Dr. Amandeep Bajwa (Department of Surgery, School of Medicine, University of Tennessee Health Science Center) for assistance in DNA extraction. Research reported in this publication was supported by National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (NIH) under award number R01DK125586 to KS. JFP is funded by the NIH under award numbers R01CA253329 and R01DK125047 . CPK is an employee of the US Department of Veterans affairs. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the Department of Veterans Affairs or the US government. The results of this paper have not been published previously in whole or part. Funding Information: We would like to thank Dr. Amandeep Bajwa (Department of Surgery, School of Medicine, University of Tennessee Health Science Center) for assistance in DNA extraction. Research reported in this publication was supported by National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (NIH) under award number R01DK125586 to KS. JFP is funded by the NIH under award numbers R01CA253329 and R01DK125047. CPK is an employee of the US Department of Veterans affairs. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the Department of Veterans Affairs or the US government. The results of this paper have not been published previously in whole or part. Publisher Copyright: © 2021 International Society of Nephrology

PY - 2021/10/1

Y1 - 2021/10/1

N2 - 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.

AB - 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.

KW - cardiovascular disease

KW - chronic kidney disease

KW - circulating microbiome

KW - end-stage renal disease

KW - inflammation

KW - mortality

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Circulating Microbial Signatures and Cardiovascular Death in Patients With ESRD

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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