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

Research output: Contribution to journalArticlepeer-review

7 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 languageEnglish (US)
Pages (from-to)2617-2628
Number of pages12
JournalKidney International Reports
Volume6
Issue number10
DOIs
StatePublished - 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

PubMed: MeSH publication types

  • Journal Article

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