TY - JOUR
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 - Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/10
Y1 - 2021/10
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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U2 - 10.1016/j.ekir.2021.07.023
DO - 10.1016/j.ekir.2021.07.023
M3 - Article
C2 - 34622101
AN - SCOPUS:85112584705
SN - 2468-0249
VL - 6
SP - 2617
EP - 2628
JO - Kidney International Reports
JF - Kidney International Reports
IS - 10
ER -
