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      Obesity-Related Renal Injury in Childhood

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          Abstract

          A significant increase in the prevalence of end-stage renal disease (ESRD) has been reported over the last three decades, paralleling the increasing prevalence of obesity and insulin resistance, also in the pediatric population. Overweight, obesity and the metabolic syndrome, which frequently coexist, contribute substantially to cardiovascular disease and ESRD. A higher body mass index, the presence of type 2 diabetes, hypertension and, of particular importance, reduced insulin sensitivity (IS), have recently emerged as strong independent risk factors for chronic kidney disease and ESRD. Of particular concern, the long-term cardiovascular impact of obesity, although deferred to adult life, has its origins in childhood. Clustering of cardiovascular risk factors is seen in children and adolescents with the highest degree of reduced IS, suggesting that adult consequences of obesity on target organs, including the kidney, are more likely to develop in these young people. This review will discuss the association between obesity and the risk of kidney disease, focusing on the way in which obesity and its metabolic complications may lead to renal involvement and injury, with particular regard to childhood. It is beyond the scope of this article to examine kidney disease as a component of syndromes that result in obesity in childhood.

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          Most cited references62

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          Obesity-related glomerulopathy: an emerging epidemic.

          We report the first large renal biopsy-based clinicopathologic study on obesity-related glomerulopathy. Obesity was defined as body mass index (BMI)> 30 kg/m2. Obesity-related glomerulopathy (ORG) was defined morphologically as focal segmental glomerulosclerosis and glomerulomegaly (O-FSGS; N = 57) or glomerulomegaly alone (O-GM; N = 14). Review of 6818 native renal biopsies received from 1986 to 2000 revealed a progressive increase in biopsy incidence of ORG from 0.2% in 1986-1990 to 2.0% in 1996-2000 (P = 0.0001). Mean BMI in ORG was 41.7 (range 30.9 to 62.7). Indications for renal biopsy included proteinuria (N = 40) or proteinuria and renal insufficiency (N = 31). Seventy-one patients with ORG were compared to 50 patients with idiopathic FSGS (I-FSGS). Patients with ORG were older (mean 42.9 vs. 32.6 years, P < 0.001) and more often Caucasian (75% vs. 52%; P = 0.003). ORG patients had a lower incidence of nephrotic range proteinuria (48% vs. 66%; P = 0.007) and nephrotic syndrome (5.6% vs. 54%; P < 0.001), with higher serum albumin (3.9 vs. 2.9 g/dL; P < 0.001), lower serum cholesterol (229 vs. 335 mg/dL; P < 0.001), and less edema (35% vs. 68%; P = 0.003). On renal biopsy, patients with ORG had fewer lesions of segmental sclerosis (10 vs. 39%; P < 0.001), more glomerulomegaly (100% vs. 10%; P < 0.001), and less extensive foot process effacement (40 vs. 75%; P < 0.001). Glomerular diameter in ORG (mean 226 mu) was significantly larger than age- and sex-matched normal controls (mean 168 mu; P < 0.001). Follow-up was available in 56 ORG patients (mean 27 months) and 50 idiopathic FSGS controls (mean 38 months). A total of 75% of ORG patients received angiotensin-converting enzyme (ACE) inhibition or A2 blockade while 78% of the I-FSGS patients received immunosuppressive therapy. ORG patients had less frequent doubling of serum creatinine (14.3% vs. 50%; P < 0.001) and progression to ESRD (3.6% vs. 42%; P < 0.001). On multivariate analysis, presenting serum creatinine and severity of proteinuria were the only predictors of poor outcome in ORG. ORG is distinct from idiopathic FSGS, with a lower incidence of nephrotic syndrome, more indolent course, consistent presence of glomerulomegaly, and milder foot process fusion. The ten-fold increase in incidence over 15 years suggests a newly emerging epidemic. Heightened physician awareness of this entity is needed to ensure accurate diagnosis and appropriate therapy.
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            Overweight, ethnicity, and the prevalence of hypertension in school-aged children.

            To describe the current prevalence of pediatric hypertension and the relationships between gender, ethnicity, overweight, and blood pressure. School-based screening was performed in 5102 children (13.5 +/- 1.7 years) from May through November 2002. Age, gender, ethnicity, weight, and height were ascertained, and body mass index (BMI) was calculated as weight (kg)/height (m2). Overweight was defined as BMI > or =95th percentile. Students with blood pressure >95th percentile on the first screening underwent a second screening 1 to 2 weeks later, and then a third screening if blood pressure was >95th percentile at the second screening. Ethnicity distribution was 44% white, 25% Hispanic, 22% African American, and 7% Asian. Overall, overweight prevalence was 20%, which varied significantly by ethnicity (31% Hispanic, 20% African American, 15% white, and 11% Asian). The prevalence of elevated blood pressure after first, second, and third screenings was 19.4%, 9.5%, and 4.5%, respectively. Elevated blood pressure on first screening was highest among Hispanics (25%) and lowest among Asians (14%). Ethnic differences in the prevalence of hypertension (elevated blood pressure on 3 screenings) were not significant after controlling for overweight. The prevalence of hypertension increased progressively as the BMI percentile increased from or =95th percentile (11%). After adjustment for gender, ethnicity, overweight, and age, the relative risk of hypertension was significant for gender (relative risk: 1.50; confidence interval: 1.15, 1.95) and overweight (relative risk: 3.26; confidence interval: 2.50, 4.24). These results confirm an evolving epidemic of cardiovascular risk in youth, as evidenced by an increase in the prevalence of overweight and hypertension, notably among ethnic minority children.
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              Association between obesity and kidney disease: a systematic review and meta-analysis.

              This study aimed to comprehensively assess epidemiologic evidence on the relation between obesity and kidney disease (KD). From 247 retrieved articles via PubMed (1980-2006), 25 cohorts, 3 cross-sectional, and 19 case-control studies met inclusion criteria. Related data were extracted using a standardized protocol. We estimated the pooled relative risk (RR) and 95% confidence interval (95% CI) of KD for each body mass index (BMI) category compared with normal weight using meta-analysis models. Population attributable risk was also calculated. Compared with normal-weight individuals (18.5
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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2010
                April 2010
                14 April 2010
                : 73
                : 5
                : 303-311
                Affiliations
                Department of Pediatrics, University of Chieti, Chieti, Italy
                Article
                308161 Horm Res Paediatr 2010;73:303–311
                10.1159/000308161
                20389099
                675b46be-58f8-4b7b-9466-4a7fc8ac20af
                © 2010 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 24 July 2009
                : 18 December 2009
                Page count
                Figures: 1, References: 85, Pages: 9
                Categories
                Mini Review

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Renal injury,Obesity, children,Insulin sensitivity

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