Abstract
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 N-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, p < 0.05) and pulse-wave velocity (4.1 vs. 3.8 m/s, p < 0.05), but lower TMAO urinary level (209 vs. 344 ng/mg creatinine, p < 0.05) than those with stage G1. Urinary TMAO level was correlated with the abundances of genera Bifidobacterium (r = 0.307, p = 0.004) and Lactobacillus (r = 0.428, p < 0.001). CKD children with abnormal ABPM profile had a lower abundance of the Prevotella genus than those with normal ABPM (p < 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.
Highlights
Children and adolescents with chronic kidney disease (CKD) are at high risk of developing cardiovascular disease (CVD) [1]
The key findings are as follows: (1) 65% of children and adolescents with CKD stage G1–G3 had BP abnormalities on ambulatory blood-pressure monitoring (ABPM); (2) pulse-wave velocity (PWV), an arterial-stiffness index, was significantly elevated in children with CKD stage G2–G3 compared to those with stage G1; (3) children with CKD stage G2–G3 had a lower urinary level of DMA and trimethylamine N-oxide (TMAO); (4) CKD children with an abnormal ABPM profile had lower abundance of the genus Prevotella than those with normal ABPM; and (5) the abundances of genera Bifidobacterium and Lactobacillus were correlated with urinary TMAO level
We found that decreased abundance of the genus Prevotella was noted in CKD children with an abnormal ABPM profile, which was in agreement with a previous study showing that the genus Prevotella is associated with CVD risk [28]
Summary
Children and adolescents with chronic kidney disease (CKD) are at high risk of developing cardiovascular disease (CVD) [1]. Examples of structural and functional markers are the noninvasive measurement of blood-pressure (BP) load, arterial stiffness, and vascular phenotype [2]. We and others have shown that more than half of children and adolescents with mild-to-moderate CKD develop abnormal BP patterns on 24 h ambulatory blood-pressure monitoring (ABPM) [3,4]. Arterial-stiffness indices, such as pulse-wave velocity (PWV) and ABPM-derived arterial-stiffness index (AASI), have been linked to known risk factors of CVD in adult CKD patients [7]. High PWV and CKD have been reported as predictors of CV events in adult patients [8], it remains unclear whether various arterial-stiffness indices are related to cardiovascular risk in children with early-stage CKD
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