Abstract
Both kidney disease and hypertension can originate from early life. Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease (CKD) in children. Since gut microbiota and their metabolite short chain fatty acids (SCFAs) have been linked to CKD and hypertension, we examined whether gut microbial composition and SCFAs are correlated with blood pressure (BP) load and renal outcome in CKD children with CAKUT. We enrolled 78 children with CKD stage G1–G4. Up to 65% of children with CAKUT had BP abnormalities on 24 h ambulatory blood pressure monitoring (ABPM). CKD children with CAKUT had lower risk of developing BP abnormalities and CKD progression than those with non-CAKUT. Reduced plasma level of propionate was found in children with CAKUT, which was related to increased abundance of phylum Verrucomicrobia, genus Akkermansia, and species Bifidobacterium bifidum. CKD children with abnormal ABPM profile had higher plasma levels of propionate and butyrate. Our findings highlight that gut microbiota-derived SCFAs like propionate and butyrate are related to BP abnormalities in children with an early stage of CKD. Early assessments of these microbial markers may aid in developing potential targets for early life intervention for lifelong hypertension prevention in childhood CKD.
Highlights
Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a various group of structural malformations that are characterized by defects in fetal kidney development [1]
CAKUT adolescents had a lower estimated glomerular filtration rate (eGFR) but a higher rate of chronic kidney disease (CKD) progression compared to children
Consistent with a previous study showing that patients with CAKUT survived longer than non-CAKUT controls due to lower cardiovascular mortality [5,6], our results showed the proportion of blood pressure (BP) abnormalities and CKD progression was lower in children with CAKUT than in those with non-CAKUT
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a various group of structural malformations that are characterized by defects in fetal kidney development [1]. Hypertension is associated with a high risk of developing cardiovascular disease (CVD) and more rapid progression of CKD [9,10]. Surrogate markers, such as noninvasive measurement of blood pressure (BP) load, arterial stiffness, and vascular phenotype [11], are essential to manage and stratify risk for CVD in pediatric CKD. Prematurity and low birth weight have relatively increased risk for the development of CAKUT, CKD, as well as hypertension later in life [13,14,15]. A better understanding of the factors linking CAKUT to hypertension in early stage of CKD is essential to developing potential interventions to halt the growing epidemic of CKD-related diseases
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