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

Kidney Int Rep. 2021 Aug 4;6(10):2617-2628. doi: 10.1016/j.ekir.2021.07.023. eCollection 2021 Oct.

Authors

Keiichi Sumida¹, Joseph F Pierre^{2

3}, Zhongji Han¹, Tahliyah S Mims², Praveen Kumar Potukuchi¹, Melana Yuzefpolskaya⁴, Paolo C Colombo⁴, Ryan T Demmer^{5

6}, Susmita Datta⁷, Csaba P Kovesdy^{1

8}

Affiliations

¹ Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
² Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
³ Department of Microbiology, Immunology, and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
⁴ Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York, New York, USA.
⁵ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
⁶ Division of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
⁷ Department of Biostatistics, University of Florida, Gainesville, Florida, USA.
⁸ Nephrology Section, Memphis VA Medical Center, Memphis, Tennessee, USA.

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.

Keywords: cardiovascular disease; chronic kidney disease; circulating microbiome; end-stage renal disease; inflammation; mortality.

Grants and funding

R01 DK125586/DK/NIDDK NIH HHS/United States