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      Estimated glomerular filtration rate and cardiometabolic risk factors in a longitudinal cohort of children

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          Abstract

          Associations between glomerular filtration rate (GFR) and cardiometabolic risk factors have been reported in adult and pediatric patients with renal disease. We aimed to assess the relationship between the estimated GFR (eGFR) and cardiometabolic risk factors in apparently healthy children. A longitudinal study in 401 asymptomatic Caucasian children (mean age 8 years) followed up after 4 years (mean age 12 years). GFR was estimated using the pediatric form of the FAS-equation. Children were classified at baseline according to their obesity status (normal weight and overweight) and according to eGFR levels (lower, average, and higher). The association of eGFR with anthropometric data [body mass index (BMI) and waist], blood pressure [systolic (SBP) and diastolic (DBP)], metabolic parameters [glucose, insulin resistance (HOMA-IR) and serum lipids], and renal ultrasonography measurements were assessed at baseline and follow-up. Baseline eGFR associated with several cardiometabolic risk factors at follow-up including higher waist, SBP, HOMA-IR, and kidney size (all p < 0.0001) in both normal weight and overweight children. In multivariate analysis, baseline eGFR was independently associated with follow-up HOMA-IR and SBP in both normal weight and overweight subjects (model R 2: 0.188–0.444), and with follow-up BMI and waist in overweight subjects (model R 2: 0.367–0.477). Moreover, children with higher filtration rates at baseline showed higher waist, SBP, DBP, HOMA-IR and renal size both at baseline and follow-up. eGFR is related to insulin resistance, blood pressure and adiposity measures in school-age children. eGFR may help to profile the cardiometabolic risk of children.

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          Kidney measures beyond traditional risk factors for cardiovascular prediction: A collaborative meta-analysis

          Background The utility of estimated glomerular filtration rate (eGFR) and albuminuria for cardiovascular prediction is controversial. Methods We meta-analyzed individual-level data from 24 cohorts (with a median follow-up time longer than 4 years, varying from 4.2 to 19.0 years) in the Chronic Kidney Disease Prognosis Consortium (637,315 participants without a history of cardiovascular disease) and assessed C-statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in 5-year timeframe, contrasting prediction models consisting of traditional risk factors with and without creatinine-based eGFR and/or albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria). Findings The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR and more evident for cardiovascular mortality (c-statistic difference 0.0139 [95%CI 0.0105–0.0174] and 0.0065 [0.0042–0.0088], respectively) and heart failure (0.0196 [0.0108–0.0284] and 0.0109 [0.0059–0.0159]) than for coronary disease (0.0048 [0.0029–0.0067] and 0.0036 [0.0019–0.0054]) and stroke (0.0105 [0.0058–0.0151] and 0.0036 [0.0004–0.0069]). Dipstick proteinuria demonstrated smaller improvement than ACR. The discrimination improvement with kidney measures was especially evident in individuals with diabetes or hypertension but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these conditions. In participants with chronic kidney disease (CKD), the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the c-statistic for cardiovascular mortality declined by 0.023 [0.016–0.030] vs. <0.007 when omitting eGFR and ACR vs. any single modifiable traditional predictors, respectively. Interpretation Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when they are already assessed for clinical purpose and/or cardiovascular mortality and heart failure are the outcomes of interest (e.g., the European guidelines on cardiovascular prevention). ACR may have particularly broad implications for cardiovascular prediction. In CKD populations, the simultaneous assessment of eGFR and ACR will facilitate improved cardiovascular risk classification, supporting current CKD guidelines. Funding US National Kidney Foundation and NIDDK
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            The impact of insulin resistance on the kidney and vasculature

            Insulin resistance is a systemic disorder that affects many organs and insulin-regulated pathways. The disorder is characterized by a reduced action of insulin despite increased insulin concentrations (hyperinsulinaemia). The effects of insulin on the kidney and vasculature differ in part from the effects on classical insulin target organs. Insulin causes vasodilation by enhancing endothelial nitric oxide production through activation of the phosphatidylinositol 3-kinase pathway. In insulin-resistant states, this pathway is impaired and the mitogen-activated protein kinase pathway stimulates vasoconstriction. The action of insulin on perivascular fat tissue and the subsequent effects on the vascular wall are not fully understood, but the hepatokine fetuin-A, which is released by fatty liver, might promote the proinflammatory effects of perivascular fat. The strong association of salt-sensitive arterial hypertension with insulin resistance indicates an involvement of the kidney in the insulin resistance syndrome. The insulin receptor is expressed on renal tubular cells and podocytes and insulin signalling has important roles in podocyte viability and tubular function. Renal sodium transport is preserved in insulin resistance and contributes to the salt-sensitivity of blood pressure in hyperinsulinaemia. Therapeutically, renal and vascular insulin resistance can be improved by an integrated holistic approach aimed at restoring overall insulin sensitivity and improving insulin signalling.
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              Prevalence of cardiovascular disease risk factors among US adolescents, 1999-2008.

              Overweight and obesity during adolescence are associated with an increased risk for cardiovascular disease (CVD) risk factors. The objective of this study was to examine the recent trends in the prevalence of selected biological CVD risk factors and the prevalence of these risk factors by overweight/obesity status among US adolescents. The NHANES is a cross-sectional, stratified, multistage probability sample survey of the US civilian, noninstitutionalized population. The study sample included 3383 participants aged 12 to 19 years from the 1999 through 2008 NHANES. Among the US adolescents aged 12 to 19 years, the overall prevalence was 14% for prehypertension/hypertension, 22% for borderline-high/high low-density lipoprotein cholesterol, 6% for low high-density lipoprotein cholesterol (<35 mg/dL), and 15% for prediabetes/diabetes during the survey period from 1999 to 2008. No significant change in the prevalence of prehypertension/hypertension (17% and 13%) and borderline-high/high low-density lipoprotein cholesterol (23% and 19%) was observed from 1999-2000 to 2007-2008, but the prevalence of prediabetes/diabetes increased from 9% to 23%. A consistent dose-response increase in the prevalence of each of these CVD risk factors was observed by weight categories: the estimated 37%, 49%, and 61% of the overweight, obese, and normal-weight adolescents, respectively, had at least 1 of these CVD risk factors during the 1999 through 2008 study period. The results of this national study indicate that US adolescents carry a substantial burden of CVD risk factors, especially those youth who are overweight or obese.
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                Author and article information

                Contributors
                alopezbermejo@idibgi.org
                jbassols@idibgi.org
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                3 June 2021
                3 June 2021
                2021
                : 11
                : 11702
                Affiliations
                [1 ]GRID grid.429182.4, Pediatric Endocrinology Research Group, , Girona Biomedical Research Institute (IDIBGI), ; 17190 Salt, Spain
                [2 ]Pediatrics, Dr. Trueta University Hospital, 17007 Girona, Spain
                [3 ]GRID grid.429182.4, Maternal-Fetal Metabolic Research Group, , Girona Biomedical Research Institute (IDIBGI), ; Parc Hospitalari Martí I Julià, Edifici M2, 17190 Salt, Spain
                [4 ]GRID grid.5596.f, ISNI 0000 0001 0668 7884, Department of Development and Regeneration, , University of Leuven, ; 3000 Leuven, Belgium
                [5 ]Endocrinology, Pediatric Research Institute, Sant Joan de Déu Children’s Hospital, 08950 Esplugues, Barcelona Spain
                [6 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, , CIBERDEM, ISCIII, ; 28029 Madrid, Spain
                [7 ]GRID grid.5319.e, ISNI 0000 0001 2179 7512, Department of Medical Sciences, Faculty of Medicine, , University of Girona, ; 17003 Girona, Spain
                Article
                91162
                10.1038/s41598-021-91162-x
                8175594
                34083639
                b3bf1f05-ce17-48cd-97e0-ecd6be03cc09
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 February 2021
                : 24 May 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI19/00451
                Award ID: PI20/00399
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                paediatric research,endocrine system and metabolic diseases
                Uncategorized
                paediatric research, endocrine system and metabolic diseases

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