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      Blood Pressure Abnormalities Associated with Gut Microbiota-Derived Short Chain Fatty Acids in Children with Congenital Anomalies of the Kidney and Urinary Tract

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          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.

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          Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health

          The colon is inhabited by a dense population of microorganisms, the so-called “gut microbiota,” able to ferment carbohydrates and proteins that escape absorption in the small intestine during digestion. This microbiota produces a wide range of metabolites, including short chain fatty acids (SCFA). These compounds are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids which can present straight or branched-chain conformation. Their production is influenced by the pattern of food intake and diet-mediated changes in the gut microbiota. SCFA have distinct physiological effects: they contribute to shaping the gut environment, influence the physiology of the colon, they can be used as energy sources by host cells and the intestinal microbiota and they also participate in different host-signaling mechanisms. We summarize the current knowledge about the production of SCFA, including bacterial cross-feedings interactions, and the biological properties of these metabolites with impact on the human health.
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            Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease.

            Developmental programming of non-communicable diseases is now an established paradigm. With respect to hypertension and chronic kidney disease, adverse events experienced in utero can affect development of the fetal kidney and reduce final nephron number. Low birthweight and prematurity are the most consistent clinical surrogates for a low nephron number and are associated with increased risk of hypertension, proteinuria, and kidney disease in later life. Rapid weight gain in childhood or adolescence further compounds these risks. Low birthweight, prematurity, and rapid childhood weight gain should alert clinicians to an individual's lifelong risk of hypertension and kidney disease, prompting education to minimise additional risk factors and ensuring follow-up. Birthweight and prematurity are affected substantially by maternal nutrition and health during pregnancy. Optimisation of maternal health and early childhood nutrition could, therefore, attenuate this programming cycle and reduce the global burden of hypertension and kidney disease in the future. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions.

              Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is an essential tool in the diagnosis and therapeutic monitoring of arterial hypertension in children. The statistical use of pediatric ABPM reference values has been compromised by the non-Gaussian distribution of 24-h blood pressure (BP) in children. To develop distribution-adjusted pediatric ABPM reference tables. From cross-sectional ABPM data obtained in 949 healthy children and adolescents aged 5-20 years, a set of reference tables was developed for 24-h, daytime and night-time mean values of systolic, diastolic, mean arterial BP and heart rate, utilizing the LMS method to account for the variably skewed distribution of ABPM data. Age- and gender-specific estimates of the distribution median (M), coefficient of variation (S) and degree of skewness (L) were obtained by a maximum-likelihood curve-fitting technique. The estimates of, and can be used to normalize ABPM data to gender and age or height. Re-application of the established, and values in the reference population confirmed appropriate normalization of ABPM values. Height standard deviation scores (SDS), body mass index (BMI) SDS and heart rate SDS were independent positive predictors of 24-h systolic BP SDS. Diastolic 24-h mean BP SDS showed a weak correlation with BMI SDS only. The use of LMS reference tables permits calculation of appropriate SDS values for ABPM in children. Whereas systolic 24-h BP is independently correlated with age, relative height and obesity, diastolic values are almost independent of age and relative height, and weakly associated with relative obesity.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                24 July 2019
                August 2019
                : 8
                : 8
                : 1090
                Affiliations
                [1 ]Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan
                [2 ]School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [3 ]Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan
                [4 ]Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, Taiwan
                [5 ]Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan
                Author notes
                [* ]Correspondence: tainyl@ 123456hotmail.com ; Tel.: +886-975-056-995; Fax: +886-7733-8009
                Author information
                https://orcid.org/0000-0001-7470-528X
                https://orcid.org/0000-0002-8007-6077
                https://orcid.org/0000-0002-7059-6407
                Article
                jcm-08-01090
                10.3390/jcm8081090
                6722976
                31344888
                7e894e4c-279e-44b2-a0a6-de91761f20ed
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 June 2019
                : 19 July 2019
                Categories
                Article

                ambulatory blood pressure monitoring,butyrate,congenital anomalies of the kidney and urinary tract (cakut),cardiovascular disease,children,chronic kidney disease,gut microbiota,hypertension,propionate,short chain fatty acid

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