Sumida Keiichi, Pierre Joseph F, Han Zhongji, Mims Tahliyah S, Potukuchi Praveen Kumar, Yuzefpolskaya Melana, Colombo Paolo C, Demmer Ryan T, Datta Susmita, Kovesdy Csaba P
Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Kidney Int Rep. 2021 Aug 4;6(10):2617-2628. doi: 10.1016/j.ekir.2021.07.023. eCollection 2021 Oct.
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.
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.
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, = 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).
Alterations of the circulating cell-free microbial signatures may be associated with higher premature cardiovascular mortality in ESRD.
终末期肾病（ESRD）患者的心血管发病率和死亡率异常高。越来越多的证据表明循环微生物群在心血管疾病发病机制中起作用；然而，关于其与ESRD患者过早心血管死亡的关联知之甚少。
在一项前瞻性病例对照研究中，纳入17例死于心血管事件的血液透析患者和17例匹配的血液透析对照者，他们在2.0年的中位随访期内仍存活。我们分别通过定量聚合酶链反应和16S或内转录间隔区（ITS）核糖体RNA（rRNA）测序，比较血清样本中循环微生物群（包括细菌、古菌和真菌）的水平和组成。分别使用Spearman等级相关性和多变量条件逻辑回归分析循环无细胞微生物特征与临床参数和心血管死亡的关联。
在所有（ITS检测的除外3例）受试患者的血清样本中均检测到16S和ITS rRNA。尽管病例组和对照组之间16S rRNA水平和α多样性无显著差异，但分类学分析显示两组之间群落成员存在差异，在门水平上，病例组中放线菌显著多于对照组，而变形菌显著少于对照组。放线菌门和变形菌门的比例与血浆核因子红细胞2相关因子2（Nrf2）水平显著相关（相关系数分别为-0.41和0.42，P = 0.015和0.013），并与心血管死亡风险存在微弱关联（每增加1%，调整后的优势比[95%置信区间]分别为1.12[0.98 - 1.29]和0.88[0.76 - 1.02]）。
循环无细胞微生物特征的改变可能与ESRD患者较高的过早心血管死亡率相关。
