Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA.
Department of Internal Medicine-Nephrology, Temple University, Philadelphia, Pennsylvania, USA.
Am J Nephrol. 2018;48(4):269-277. doi: 10.1159/000493862. Epub 2018 Oct 16.
The gut microbiota is altered in patients with chronic kidney disease (CKD), and cardiovascular risk increases with progressive CKD. This study examined the potential link between short chain fatty acids (SCFAs), which are produced by the gut microbiota, and cardiovascular outcomes in patients with CKD.
SCFAs were measured using a targeted liquid chromatography-mass spectrometry platform in baseline plasma samples from 214 patients with CKD enrolled in the Clinical Phenotyping Resource and Biobank Core; 81 patients with coronary artery disease (CAD) and 133 without CAD were randomly assigned to training and validation subsets. The primary outcome was a history of CAD and the secondary outcome was a composite history of cardiovascular disease (CVD) at enrollment.
We found significantly higher levels of the SCFA valerate among patients with CAD as compared with patients without CAD in the training set (p < 0.001). The valerate concentrations were also significantly higher among subjects with composite outcomes of CVD compared to those without CVD (p = 0.006). These results were subsequently replicated in the validation set. Logistic regression analysis revealed a strong independent association between plasma valerate levels and CVD in both training and validation sets. When valerate was added to the base clinical model comprising of diabetes, hypertension, urinary protein-creatinine ratio, and estimated glomerular filtration rate, it increased the c-statistics for predicting CVD from 0.68 to 0.79 (p = 0.02) in the training set, an observation which was confirmed in the validation set. -Conclusion: This study provides evidence for alterations in gut-microbiota-derived SCFAs with advancing CKD, demonstrates the association of higher plasma valerate levels with pre-existing CVD, and reveals areas for future exploration of cardiovascular risk in patients with CKD.
慢性肾脏病（CKD）患者的肠道微生物群发生改变，随着 CKD 的进展，心血管风险增加。本研究探讨了肠道微生物群产生的短链脂肪酸（SCFAs）与 CKD 患者心血管结局之间的潜在联系。
在 214 名 CKD 患者的基线血浆样本中使用靶向液相色谱-质谱平台测量 SCFAs；81 名患有冠状动脉疾病（CAD）和 133 名无 CAD 的患者被随机分配到训练集和验证集。主要结局是 CAD 病史，次要结局是入组时的心血管疾病（CVD）综合病史。
我们发现，在训练集中，CAD 患者的 SCFA 戊酸盐水平明显高于无 CAD 患者（p < 0.001）。复合 CVD 结局的受试者的戊酸盐浓度也明显高于无 CVD 受试者（p = 0.006）。这些结果随后在验证集中得到复制。逻辑回归分析显示，在训练集和验证集中，血浆戊酸盐水平与 CVD 之间存在很强的独立关联。当戊酸盐被添加到包含糖尿病、高血压、尿蛋白-肌酐比和估计肾小球滤过率的基本临床模型中时，它提高了预测 CVD 的 C 统计量，从训练集的 0.68 增加到 0.79（p = 0.02），这一观察结果在验证集中得到了证实。-结论：本研究提供了证据表明，随着 CKD 的进展，肠道微生物群衍生的 SCFAs 发生改变，证实了较高的血浆戊酸盐水平与预先存在的 CVD 相关，并揭示了未来探索 CKD 患者心血管风险的领域。
