Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan.
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2018 Nov 22;19(12):3699. doi: 10.3390/ijms19123699.
Despite cardiovascular disease (CVD) being the leading cause of morbidity and mortality in chronic kidney disease (CKD), less attention has been paid to subclinical CVD in children and adolescents with early CKD stages. Gut microbiota and their metabolite, trimethylamine -oxide (TMAO), have been linked to CVD. Ambulatory blood-pressure monitoring (ABPM) and arterial-stiffness assessment allow for early detection of subclinical CVD. We therefore investigated whether gut microbial composition and TMAO metabolic pathway are correlated with blood-pressure (BP) load and vascular abnormalities in children with early-stage CKD. We enrolled 86 children with G1⁻G3 CKD stages. Approximately two-thirds of CKD children had BP abnormalities on ABPM. Children with CKD stage G2⁻G3 had a higher uric acid level (6.6 vs. 4.8 mg/dL, < 0.05) and pulse-wave velocity (4.1 vs. 3.8 m/s, < 0.05), but lower TMAO urinary level (209 vs. 344 ng/mg creatinine, < 0.05) than those with stage G1. Urinary TMAO level was correlated with the abundances of genera ( = 0.307, = 0.004) and ( = 0.428, < 0.001). CKD children with abnormal ABPM profile had a lower abundance of the genus than those with normal ABPM ( < 0.05). Our results highlight the link between gut microbiota, microbial metabolite TMAO, BP load, and arterial-stiffness indices in children with early-stage CKD. Early assessments of these surrogate markers should aid in decreasing cardiovascular risk in childhood CKD.
尽管心血管疾病（CVD）是慢性肾脏病（CKD）患者发病率和死亡率的主要原因，但人们对早期 CKD 患儿亚临床 CVD 的关注度较低。肠道微生物群及其代谢产物三甲胺氧化物（TMAO）与 CVD 有关。动态血压监测（ABPM）和动脉僵硬度评估可早期发现亚临床 CVD。因此，我们研究了肠道微生物组成和 TMAO 代谢途径是否与早期 CKD 患儿的血压（BP）负荷和血管异常相关。我们纳入了 86 名 G1⁻G3 CKD 患儿。大约三分之二的 CKD 患儿的 ABPM 存在血压异常。CKD 分期 G2⁻G3 的患儿尿酸水平（6.6 比 4.8 mg/dL， < 0.05）和脉搏波速度（4.1 比 3.8 m/s， < 0.05）较高，但 TMAO 尿水平（209 比 344 ng/mg 肌酐， < 0.05）较低。尿 TMAO 水平与 和 属丰度呈正相关（ = 0.307， = 0.004）和 （ = 0.428， < 0.001）。ABPM 异常的 CKD 患儿的 属丰度低于 ABPM 正常的患儿（ < 0.05）。我们的结果强调了肠道微生物群、微生物代谢产物 TMAO、BP 负荷和早期 CKD 患儿动脉僵硬度指标之间的联系。早期评估这些替代标志物有助于降低儿童 CKD 的心血管风险。
