|
1
|
Phengpol N, Promsan S, Pengrattanachot N, Jaruan O, Sutthasupha P, Lungkaphin A. Maternal obesity promotes impaired renal autophagic process and kidney injury in male offspring. Int J Obes (Lond) 2025:10.1038/s41366-025-01751-3. [PMID: 40133698 DOI: 10.1038/s41366-025-01751-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 02/12/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND Obesity during pregnancy increases the risk of obesity, insulin resistance, diabetes, and the development and progression of chronic kidney disease (CKD) in later life in offspring. Impaired renal autophagic process is linked to kidney dysfunction in the setting of increased renal lipid accumulation. The aim of this study was to elucidate the effect of maternal obesity on kidney injury related to impaired renal autophagic process in the offspring. METHODS Maternal obesity model was conducted using female C57BL/6 mice fed with high-fat diet (HFD) for 8 weeks before mating. HFD was consecutively maintained throughout gestation and lactation. Male offspring were selected for investigation after weaning. Metabolic parameters and kidney morphology were performed. Renal insulin signaling, lipid metabolism, lipid accumulation, fibrosis and autophagy were determined. RESULTS Male offspring of HFD fed mothers developed obesity with insulin resistance, hyperglycemia, hyperlipidemia and consequently promoted kidney injury. Maternal obesity increased CD36, FAS, SREBP1c and Perilipin-2 while suppressed PPARα and CPT1A. The reduction of AMPK, SIRT1, Beclin-1, LC3B, and LAMP2 and the elevation of mTOR and SQSTM1/P62 were observed. These findings indicated the impairment of autophagy and renal lipid metabolism exaggerating renal lipid accumulation in the offspring of maternal obesity. CONCLUSIONS This study demonstrated that long-term HFD consumption in mothers promoted obesity with insulin resistance related kidney injury through the impairment of autophagic process and renal lipid metabolism in the offspring. These circumstances accelerated kidney injury and contributed to an increased susceptibility to CKD in male offspring of maternal obesity.
Collapse
Affiliation(s)
- Nichakorn Phengpol
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sasivimon Promsan
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Onanong Jaruan
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Prempree Sutthasupha
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Anusorn Lungkaphin
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
- Functional Foods for Health and Disease, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
- Functional Food Research Center for Well-being, Multidisciplinary Research Institute Chiang Mai University, Chiang Mai, Thailand.
| |
Collapse
|
|
2
|
Rubino F, Cummings DE, Eckel RH, Cohen RV, Wilding JPH, Brown WA, Stanford FC, Batterham RL, Farooqi IS, Farpour-Lambert NJ, le Roux CW, Sattar N, Baur LA, Morrison KM, Misra A, Kadowaki T, Tham KW, Sumithran P, Garvey WT, Kirwan JP, Fernández-Real JM, Corkey BE, Toplak H, Kokkinos A, Kushner RF, Branca F, Valabhji J, Blüher M, Bornstein SR, Grill HJ, Ravussin E, Gregg E, Al Busaidi NB, Alfaris NF, Al Ozairi E, Carlsson LMS, Clément K, Després JP, Dixon JB, Galea G, Kaplan LM, Laferrère B, Laville M, Lim S, Luna Fuentes JR, Mooney VM, Nadglowski J, Urudinachi A, Olszanecka-Glinianowicz M, Pan A, Pattou F, Schauer PR, Tschöp MH, van der Merwe MT, Vettor R, Mingrone G. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol 2025; 13:221-262. [PMID: 39824205 PMCID: PMC11870235 DOI: 10.1016/s2213-8587(24)00316-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 09/15/2024] [Accepted: 10/07/2024] [Indexed: 01/20/2025]
Abstract
Current BMI-based measures of obesity can both underestimate and overestimate adiposity and provide inadequate information about health at the individual level, which undermines medically-sound approaches to health care and policy. This Commission sought to define clinical obesity as a condition of illness that, akin to the notion of chronic disease in other medical specialties, directly results from the effect of excess adiposity on the function of organs and tissues. The specific aim of the Commission was to establish objective criteria for disease diagnosis, aiding clinical decision making and prioritisation of therapeutic interventions and public health strategies. To this end, a group of 58 experts—representing multiple medical specialties and countries—discussed available evidence and participated in a consensus development process. Among these commissioners were people with lived experience of obesity to ensure consideration of patients’ perspectives. The Commission defines obesity as a condition characterised by excess adiposity, with or without abnormal distribution or function of adipose tissue, and with causes that are multifactorial and still incompletely understood. We define clinical obesity as a chronic, systemic illness characterised by alterations in the function of tissues, organs, the entire individual, or a combination thereof, due to excess adiposity. Clinical obesity can lead to severe end-organ damage, causing life-altering and potentially life-threatening complications (eg, heart attack, stroke, and renal failure). We define preclinical obesity as a state of excess adiposity with preserved function of other tissues and organs and a varying, but generally increased, risk of developing clinical obesity and several other non-communicable diseases (eg, type 2 diabetes, cardiovascular disease, certain types of cancer, and mental disorders). Although the risk of mortality and obesity-associated diseases can rise as a continuum across increasing levels of fat mass, we differentiate between preclinical and clinical obesity (ie, health vs illness) for clinical and policy-related purposes. We recommend that BMI should be used only as a surrogate measure of health risk at a population level, for epidemiological studies, or for screening purposes, rather than as an individual measure of health. Excess adiposity should be confirmed by either direct measurement of body fat, where available, or at least one anthropometric criterion (eg, waist circumference, waist-to-hip ratio, or waist-to-height ratio) in addition to BMI, using validated methods and cutoff points appropriate to age, gender, and ethnicity. In people with very high BMI (ie, >40 kg/m2), however, excess adiposity can pragmatically be assumed, and no further confirmation is required. We also recommend that people with confirmed obesity status (ie, excess adiposity with or without abnormal organ or tissue function) should be assessed for clinical obesity. The diagnosis of clinical obesity requires one or both of the following main criteria: evidence of reduced organ or tissue function due to obesity (ie, signs, symptoms, or diagnostic tests showing abnormalities in the function of one or more tissue or organ system); or substantial, age-adjusted limitations of daily activities reflecting the specific effect of obesity on mobility, other basic activities of daily living (eg, bathing, dressing, toileting, continence, and eating), or both. People with clinical obesity should receive timely, evidence-based treatment, with the aim to induce improvement (or remission, when possible) of clinical manifestations of obesity and prevent progression to end-organ damage. People with preclinical obesity should undergo evidence-based health counselling, monitoring of their health status over time, and, when applicable, appropriate intervention to reduce risk of developing clinical obesity and other obesity-related diseases, as appropriate for the level of individual health risk. Policy makers and health authorities should ensure adequate and equitable access to available evidence-based treatments for individuals with clinical obesity, as appropriate for people with a chronic and potentially life-threatening illness. Public health strategies to reduce the incidence and prevalence of obesity at population levels must be based on current scientific evidence, rather than unproven assumptions that blame individual responsibility for the development of obesity. Weight-based bias and stigma are major obstacles in efforts to effectively prevent and treat obesity; health-care professionals and policy makers should receive proper training to address this important issue of obesity. All recommendations presented in this Commission have been agreed with the highest level of consensus among the commissioners (grade of agreement 90–100%) and have been endorsed by 76 organisations worldwide, including scientific societies and patient advocacy groups.
Collapse
Affiliation(s)
- Francesco Rubino
- Metabolic and Bariatric Surgery, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK; King's College Hospital, London, UK.
| | - David E Cummings
- University of Washington, Seattle, WA, USA; Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Robert H Eckel
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ricardo V Cohen
- Center for the Treatment of Obesity and Diabetes, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | - John P H Wilding
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
| | - Wendy A Brown
- Monash University Department of Surgery, Central Clinical School, Alfred Health, Melbourne, VIC, Australia
| | - Fatima Cody Stanford
- Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Endocrinology, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Rachel L Batterham
- International Medical Affairs, Eli Lilly, Basingstoke, UK; Diabetes and Endocrinology, University College London, London, UK
| | - I Sadaf Farooqi
- Institute of Metabolic Science and National Institute for Health and Care Research, Cambridge Biomedical Research Centre at Addenbrookes Hospital, Cambridge, UK
| | - Nathalie J Farpour-Lambert
- Obesity Prevention and Care Program, Department of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - Carel W le Roux
- Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland
| | - Naveed Sattar
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Louise A Baur
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Weight Management Services, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Katherine M Morrison
- Centre for Metabolism, Obesity and Diabetes Research, Department of Pediatrics, McMaster University, Hamilton, ON, Canada; McMaster Children's Hospital, Hamilton, ON, Canada
| | - Anoop Misra
- Fortis C-DOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes Obesity and Cholesterol Foundation, New Delhi, India; Diabetes Foundation New Delhi, India
| | | | - Kwang Wei Tham
- Department of Endocrinology, Woodlands Health, National Healthcare Group, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Priya Sumithran
- Department of Surgery, School of Translational Medicine, Monash University, Melbourne, VIC, Australia; Department of Endocrinology and Diabetes, Alfred Health, Melbourne, VIC, Australia
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - John P Kirwan
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - José-Manuel Fernández-Real
- CIBER Pathophysiology of Obesity and Nutrition, Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain; Hospital Trueta of Girona and Institut d'Investigació Biomèdica de Girona, Girona, Spain
| | - Barbara E Corkey
- Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA
| | - Hermann Toplak
- Division of Endocrinology and Diabetology, Department of Medicine, University of Graz, Graz, Austria
| | - Alexander Kokkinos
- First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Robert F Kushner
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Francesco Branca
- Department of Nutrition and Food Safety, World Health Organization, Geneva, Switzerland
| | - Jonathan Valabhji
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK; Department of Diabetes and Endocrinology, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, UK
| | - Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research of Helmholtz Munich, University of Leipzig and University Hospital Leipzig, Leipzig, Germany
| | - Stefan R Bornstein
- Department of Internal Medicine III, Carl Gustav Carus University Hospital Dresden, Technical University Dresden, Dresden, Germany; School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Harvey J Grill
- Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA
| | - Eric Ravussin
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - Edward Gregg
- School of Population Health, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland; School of Public Health, Imperial College London, London, UK
| | - Noor B Al Busaidi
- National Diabetes and Endocrine Center, Royal Hospital, Muscat, Oman; Oman Diabetes Association, Muscat, Oman
| | - Nasreen F Alfaris
- Obesity Endocrine and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ebaa Al Ozairi
- Clinical Research Unit, Dasman Diabetes Institute, Dasman, Kuwait
| | - Lena M S Carlsson
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Karine Clément
- Nutrition and Obesities: Systemic Approaches, NutriOmics Research Group, INSERM, Sorbonne Université, Paris, France; Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique-Hospital of Paris, Paris, France
| | | | - John B Dixon
- Iverson Health Innovation Research institute, Swinburne University of Technology, Melbourne, VIC, Australia
| | - Gauden Galea
- Regional Office for Europe, World Health Organization, Geneva, Switzerland
| | - Lee M Kaplan
- Section on Obesity Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Blandine Laferrère
- Division of Endocrinology, Columbia University Irving Medical Center, New York, NY, USA
| | | | - Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seoul, South Korea
| | | | - Vicki M Mooney
- European Coalition for people Living with Obesity, Dublin, Ireland
| | | | - Agbo Urudinachi
- Department of Community Health, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Nigeria
| | - Magdalena Olszanecka-Glinianowicz
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Science, Medical University of Silesia, Katowice, Poland
| | - An Pan
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Francois Pattou
- Translational Research for Diabetes, Lille University, Lille University Hospital, Inserm, Institut Pasteur Lille, Lille, France; Department of General and Endocrine Surgery, Lille University Hospital, Lille, France
| | | | - Matthias H Tschöp
- Helmholtz Munich, Munich, Germany; Technical University of Munich, Munich, Germany
| | - Maria T van der Merwe
- University of Pretoria, Pretoria, South Africa; Nectare Waterfall City Hospital, Midrand, South Africa
| | - Roberto Vettor
- Internal Medicine, Center for the Study and the Integrated Treatment of Obesity, Department of Medicine, University of Padova, Padua, Italy; Center for Metabolic and Nutrition Related Diseases,Humanitas Research Hospital, Milan, Italy
| | - Geltrude Mingrone
- Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK; Catholic University of the Sacred Heart, Rome, Italy; University Polyclinic Foundation Agostino Gemelli IRCCS, Rome, Italy
| |
Collapse
|
|
3
|
Bizerea-Moga TO, Pitulice L, Bizerea-Spiridon O, Moga TV. Exploring the Link between Oxidative Stress, Selenium Levels, and Obesity in Youth. Int J Mol Sci 2024; 25:7276. [PMID: 39000383 PMCID: PMC11242909 DOI: 10.3390/ijms25137276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
Obesity is a worldwide increasing concern. Although in adults this is easily estimated with the body mass index, in children, who are constantly growing and whose bodies are changing, the reference points to assess weight status are age and gender, and need corroboration with complementary data, making their quantification highly difficult. The present review explores the interaction spectrum of oxidative stress, selenium status, and obesity in children and adolescents. Any factor related to oxidative stress that triggers obesity and, conversely, obesity that induces oxidative stress are part of a vicious circle, a complex chain of mechanisms that derive from each other and reinforce each other with serious health consequences. Selenium and its compounds exhibit key antioxidant activity and also have a significant role in the nutritional evaluation of obese children. The balance of selenium intake, retention, and metabolism emerges as a vital aspect of health, reflecting the complex interactions between diet, oxidative stress, and obesity. Understanding whether selenium status is a contributor to or a consequence of obesity could inform nutritional interventions and public health strategies aimed at preventing and managing obesity from an early age.
Collapse
Affiliation(s)
- Teofana Otilia Bizerea-Moga
- Department XI of Pediatrics-1st Pediatric Discipline, Center for Research on Growth and Developmental Disorders in Children, ‘Victor Babeș’ University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq No 2, 300041 Timișoara, Romania;
- 1st Pediatric Clinic, ‘Louis Țurcanu’ Children’s Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timișoara, Romania
| | - Laura Pitulice
- Department of Biology-Chemistry, West University of Timişoara, Pestallozi 16, 300115 Timişoara, Romania;
- The Institute for Advanced Environmental Research (ICAM), Popa Şapcă 4C, 300054 Timişoara, Romania
| | - Otilia Bizerea-Spiridon
- Department of Biology-Chemistry, West University of Timişoara, Pestallozi 16, 300115 Timişoara, Romania;
- The Institute for Advanced Environmental Research (ICAM), Popa Şapcă 4C, 300054 Timişoara, Romania
| | - Tudor Voicu Moga
- Department VII of Internal Medicine-Gastroenterology Discipline, Advanced Regional Research Center in Gastroenterology and Hepatology, ‘Victor Babeș’ University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq No 2, 300041 Timișoara, Romania;
- Gastroenterology and Hepatology Clinic, ‘Pius Brînzeu’ County Emergency Clinical Hospital, Liviu Rebreanu 156, 300723 Timișoara, Romania
| |
Collapse
|
|
4
|
Ekperikpe US, Mandal S, Bhopatkar AA, Shields CA, Coley CA, Chambers CL, Johnson TD, Cornelius DC, Williams JM. Abatacept Decreases Renal T-cell Infiltration and Renal Inflammation and Ameliorates Progressive Renal Injury in Obese Dahl Salt-sensitive Rats Before Puberty. J Cardiovasc Pharmacol 2024; 83:635-645. [PMID: 38547515 DOI: 10.1097/fjc.0000000000001565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 03/01/2024] [Indexed: 11/01/2024]
Abstract
ABSTRACT Prepubertal obesity is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive (SS) leptin receptor mutant (SS LepR mutant) rats was associated with increased T-cell infiltration and activation before puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SS LepR mutant rats before puberty. Four-week-old SS and SS LepR mutant rats were treated with IgG or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Abatacept reduced the renal infiltration of T cells by almost 50% in SS LepR mutant rats. Treatment with abatacept decreased the renal expression of macrophage inflammatory protein-3 alpha while increasing IL-4 in SS LepR mutant rats without affecting SS rats. While not having an impact on blood glucose levels, abatacept reduced hyperinsulinemia and plasma triglycerides in SS LepR mutant rats without affecting SS rats. We did not observe any differences in the mean arterial pressure among the groups. Proteinuria was markedly higher in SS LepR mutant rats than in SS rats throughout the study, and treatment with abatacept decreased proteinuria by about 40% in SS LepR mutant rats without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SS LepR mutant rats versus SS rats, and chronic treatment with abatacept significantly reduced these renal abnormalities in SS LepR mutant rats. These data suggest that renal T-cell activation contributes to the early progression of renal injury associated with prepubertal obesity.
Collapse
Affiliation(s)
- Ubong S Ekperikpe
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS
| | | | | | | | | | | | | | | | | |
Collapse
|
|
5
|
Kong R, Li S. Effects of childhood obesity on heart failure and its associated risk factors in the European population: A Mendelian randomization study. Nutr Metab Cardiovasc Dis 2024; 34:1080-1087. [PMID: 38233270 DOI: 10.1016/j.numecd.2023.11.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 11/10/2023] [Accepted: 11/30/2023] [Indexed: 01/19/2024]
Abstract
BACKGROUND AND AIMS Observational studies have shown that obesity considerably affects the cardiovascular system. Thus we conducted this Mendelian randomization (MR) analysis to evaluate the causal effect of childhood obesity on heart failure (HF) and its risk factors. METHODS AND RESULTS We obtained genetic instruments from genome-wide association studies (GWAS) that investigated childhood obesity, HF, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), chronic kidney disease (CKD), valvular heart disease, myocarditis, hypertrophic cardiomyopathy, and hyperthyroidism. Inverse variance weighting (IVW), weighted median analysis, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were employed for MR analyses. In addition, the leave-one-out sensitivity test, MR-PRESSO global test, and Cochran's Q test were used for sensitivity analyses. Genetic evaluations showed that childhood obesity increases the risk of HF (odds ratio [OR] = 1.11, 95%CI: 1.05-1.17, p = 1.26 × 10-4), T2DM (OR = 1.17, 95%CI: 1.12-1.23, p = 8.80 × 10-12), AF (OR = 1.08, 95%CI: 1.05-1.12, p = 2.66 × 10-7), MI (OR = 1.08, 95%CI: 1.04-1.13, p = 3.35 × 10-4), and CAD (OR = 1.08, 95%CI: 1.03-1.13, p = 1.48 × 10-3). We found no association between childhood obesity and CKD, valvular heart disease, myocarditis, hypertrophic cardiomyopathy, or hyperthyroidism. Sensitivity analysis and Bonferroni's correction showed consistent results. CONCLUSIONS Our study provides new evidence for the relationship between childhood obesity and HF and its risk factors. The results indicate that individuals with a history of childhood obesity require more clinical attention to prevent the development of HF.
Collapse
Affiliation(s)
- Renjing Kong
- Department of Geriatrics, The Second Xiangya Hospital, Institute of Aging and Age-Related Disease Research, Central South University, Changsha, Hunan 410011, China
| | - Shuang Li
- Department of Geriatrics, The Second Xiangya Hospital, Institute of Aging and Age-Related Disease Research, Central South University, Changsha, Hunan 410011, China.
| |
Collapse
|
|
6
|
Di Sessa A, Passaro AP, Colasante AM, Cioffi S, Guarino S, Umano GR, Papparella A, Miraglia Del Giudice E, Marzuillo P. Kidney damage predictors in children with metabolically healthy and metabolically unhealthy obesity phenotype. Int J Obes (Lond) 2023; 47:1247-1255. [PMID: 37689826 DOI: 10.1038/s41366-023-01379-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 08/25/2023] [Accepted: 08/30/2023] [Indexed: 09/11/2023]
Abstract
BACKGROUND Obesity and kidney damage have been closely linked in adults, but little is still known in childhood. OBJECTIVE To identify predictors of kidney damage in children with metabolically healthy (MHO) and metabolically unhealthy (MUO) obesity phenotypes. METHODS We retrospectively examined 396 children with obesity (mean age 10.72 ± 2.71 years, body mass index-standard deviation score, BMI-SDS, 2.23 ± 0.57) stratified according to metabolic phenotypes. Kidney damage was defined as the presence of reduced estimated glomerular filtration rate (eGFR < 90 mL/min/1.73m2) and/or albuminuria (≥ 30 mg/g urinary creatinine). RESULTS Kidney damage was found in 20.9% of the study population. Children with kidney damage had higher BMI-SDS, homeostasis model assessment of insulin resistance (HOMA-IR), and inflammation markers levels and increased prevalence of non-alcoholic fatty liver disease (NAFLD) than those without kidney damage (all p < 0.005). MUO and MHO subjects had respectively an odds ratio (OR) to show kidney damage of of 1.92 (95%CI:1.22-3.01; p = 0.005) and 1.05 (95%CI:1.00-1.09; p = 0.028) after adjustments. Moreover, we found that only HOMA-IR was closely associated to kidney damage in MUO group (OR = 2.07;95%CI:1.20-3.57; p = 0.007), while HOMA-IR (OR = 1.15;95%CI:1.02-1.29; p = 0.011) and uric acid (OR = 1.15;95% CI:1.02-1.30; p = 0.010) were the only significant risk factors for kidney damage in MHO group. CONCLUSION An increased risk of kidney damage has been observed in children with obesity and in particular in those with MUO phenotype. As their role on kidney function, HOMA-IR should be monitored in MUO children and both HOMA-IR and uric acid in MHO children.
Collapse
Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Antonio Paride Passaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Alberto Maria Colasante
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Alfonso Papparella
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| |
Collapse
|
|
7
|
Tang R, Wang X, Li X, Ma H, Liang Z, Heianza Y, Qi L. Adherence to Life's Essential 8 and incident chronic kidney disease: a prospective study of 147,988 UK Biobank participants. Am J Clin Nutr 2023; 118:804-811. [PMID: 37604298 PMCID: PMC10579043 DOI: 10.1016/j.ajcnut.2023.08.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 08/09/2023] [Accepted: 08/14/2023] [Indexed: 08/23/2023] Open
Abstract
BACKGROUND The American Heart Association recently updated Life's Essential 8 (LE8) score. This amalgamation of health factors, recognized for their individual associations with chronic kidney disease (CKD) risk, provides a robust tool to assess overall cardiovascular health (CVH), which could potentially be extrapolated to predict CKD risk. OBJECTIVES This study aimed to investigate the association between levels of CVH, as measured by the LE8 score, and risk of CKD in the UK Biobank. METHODS A total of 147,988 participants free of CKD and cardiovascular disease from the UK Biobank were included in this prospective study. CVH levels were categorized as low (0-49), moderate (50-79), and high (80-100) using LE8 score. An adjusted Cox proportional hazard model was used to investigate the association between LE8 and CKD. The population attributable-risk (PAR) was also calculated. RESULTS During a median follow-up of 10 y, 1936 CKD cases were documented. A higher LE8 score was associated with a significant lower risk of CKD (P < 0.001), and a linear dose-response relationship was observed. Similar patterns were also found in the associations of the LE8 behavior and biological subscale scores with CKD. Compared with participants with a low CVH category, participants with a moderate CVH were associated with a 39% lower risk of developing CKD (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.52, 0.72); and those with a high CVH had a 57% lower risk of CKD incidence (HR: 0.43; 95% CI: 0.35, 0.53) after adjustment for covariates. Among 8 distinct metrics of LE8 score, the BMI metric had the highest PAR (24.6%; 95% CI: 18.8, 30.2). Of the total CKD risk, 3.2% (95% CI: 1.4, 5.0) was attributable to inadequate or excessive sleep duration. CONCLUSIONS High CVH, defined by LE8, is significantly associated with a lower risk of CKD. These results suggest that promoting optimal cardiovascular health may lower the burden of CKD.
Collapse
Affiliation(s)
- Rui Tang
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - Xuan Wang
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - Xiang Li
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - Hao Ma
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - Zhaoxia Liang
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States; Department of Obstetrical, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yoriko Heianza
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
| |
Collapse
|
|
8
|
Ekperikpe US, Mandal S, Holt SJ, Daniels JK, Johnson TD, Cooper JS, Safir SM, Cornelius DC, Williams JM. Metformin reduces insulin resistance and attenuates progressive renal injury in prepubertal obese Dahl salt-sensitive rats. Am J Physiol Renal Physiol 2023; 325:F363-F376. [PMID: 37498548 PMCID: PMC10639024 DOI: 10.1152/ajprenal.00078.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/12/2023] [Accepted: 07/24/2023] [Indexed: 07/28/2023] Open
Abstract
Prepubertal obesity is currently an epidemic and is considered as a major risk factor for renal injury. Previous studies have demonstrated that insulin resistance contributes to renal injury in obesity, independent of diabetes. However, studies examining the relationship between insulin resistance and renal injury in obese children are lacking. Recently, we reported that progressive renal injury in Dahl salt-sensitive (SS) leptin receptor mutant (SSLepRmutant) rats was associated with insulin resistance before puberty. Therefore, the aim of the present study was to examine whether decreasing insulin resistance with metformin will reduce renal injury in SSLepRmutant rats. Four-wk-old SS and SSLepRmutant rats were separated into the following two groups: 1) vehicle and 2) metformin (300 mg/kg/day) via chow diet for 4 wk. Chronic administration of metformin markedly reduced insulin resistance and dyslipidemia in SSLepRmutant rats. We did not detect any differences in mean arterial pressure between vehicle and metformin-treated SS and SSLepRmutant rats. Proteinuria was significantly greater in SSLepRmutant rats versus SS rats throughout the study, and metformin administration significantly reduced proteinuria in SSLepRmutant rats. At the end of the protocol, metformin prevented the renal hyperfiltration observed in SSLepRmutant rats versus SS rats. Glomerular and tubular injury and renal inflammation and fibrosis were significantly higher in vehicle-treated SSLepRmutant rats versus SS rats, and metformin reduced these parameters in SSLepRmutant rats. These data suggest that reducing insulin resistance with metformin prevents renal hyperfiltration and progressive renal injury in SSLepRmutant rats before puberty and may be therapeutically useful in managing renal injury during prepubertal obesity.NEW & NOTEWORTHY Childhood/prepubertal obesity is a public health concern that is associated with early signs of proteinuria. Insulin resistance has been described in obese children. However, studies investigating the role of insulin resistance during childhood obesity-associated renal injury are limited. This study provides evidence of an early relationship between insulin resistance and renal injury in a rat model of prepubertal obesity. These data also suggest that reducing insulin resistance with metformin may be renoprotective in obese children.
Collapse
Affiliation(s)
- Ubong S Ekperikpe
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Sautan Mandal
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Stephen J Holt
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Jacori K Daniels
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Tyler D Johnson
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Jonita S Cooper
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Sarah M Safir
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Denise C Cornelius
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| | - Jan M Williams
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States
| |
Collapse
|
|
9
|
Dachy A, Van Loo L, Mekahli D. Autosomal Dominant Polycystic Kidney Disease in Children and Adolescents: Assessing and Managing Risk of Progression. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:236-244. [PMID: 37088526 DOI: 10.1053/j.akdh.2023.01.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/07/2023] [Accepted: 01/19/2023] [Indexed: 04/25/2023]
Abstract
The clinical management of autosomal dominant polycystic kidney disease (ADPKD) in adults has shifted from managing complications to delaying disease progression through newly emerging therapies. Regarding pediatric management of the disease, there are still specific hurdles related to the management of children and adolescents with ADPKD and, unlike adults, there are no specific therapies for pediatric ADPKD or stratification models to identify children and young adults at risk of rapid decline in kidney function. Therefore, early identification and management of factors that may modify disease progression, such as hypertension and obesity, are of most importance for young children with ADPKD. Many of these risk factors could promote disease progression in both ADPKD and chronic kidney disease. Hence, nephroprotective measures applied early in life can represent a window of opportunity to prevent the decline of the glomerular filtration rate especially in young patients with ADPKD. In this review, we highlight current challenges in the management of patients with pediatric ADPKD, the importance of early modifying factors in disease progression as well as the gaps and future perspectives in the pediatric ADPKD research field.
Collapse
Affiliation(s)
- Angélique Dachy
- PKD Research Group, Department of Cellular and MoleculMedar icine, KU Leuven, Leuven, Belgium; Department of Pediatrics, ULiège Academic Hospital, Liège, Belgium; Laboratory of Translational Research in Nephrology (LTRN), GIGA Cardiovascular Sciences, ULiège, Liège, Belgium
| | - Liselotte Van Loo
- Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium.
| | - Djalila Mekahli
- PKD Research Group, Department of Cellular and MoleculMedar icine, KU Leuven, Leuven, Belgium; Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium.
| |
Collapse
|
|
10
|
Ekperikpe US, Poudel B, Shields CA, Mandal S, Cornelius DC, Williams JM. Neutralizing MIP3 α Reduces Renal Immune Cell Infiltration and Progressive Renal Injury in Young Obese Dahl Salt-Sensitive Rats. J Pharmacol Exp Ther 2023; 384:445-454. [PMID: 36507846 PMCID: PMC9976792 DOI: 10.1124/jpet.122.001298] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 11/21/2022] [Accepted: 11/23/2022] [Indexed: 12/12/2022] Open
Abstract
Recently, we reported that the early progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats was associated with increased macrophage inflammatory protein 3-α (MIP3α) expression prior to puberty. Therefore, this study tested the hypothesis that MIP3α plays a role in recruiting immune cells, thereby triggering renal inflammation and early progressive renal injury in SSLepRmutant rats prior to puberty. Four-week-old Dahl salt-sensitive (SS) and SSLepRmutant rats either served as control (IgG; intraperitoneal, every other day) or received MIP3α-neutralizing antibody (MNA; 100 µg/kg) for 4 weeks. MNA reduced circulating and renal MIP3α levels and proinflammatory immune cells by 50%. Although MNA treatment did not affect blood glucose and plasma cholesterol levels, MNA markedly decreased insulin resistance and triglyceride levels in SSLepRmutant rats. We observed no differences in mean arterial pressure (MAP) between SS and SSLepRmutant rats, and MNA had no effect on MAP in either strain. Proteinuria was significantly increased in SSLepRmutant rats versus SS rats over the course of the study. Treatment with MNA markedly decreased proteinuria in SSLepRmutant rats while not affecting SS rats. Also, MNA decreased glomerular and tubular injury and renal fibrosis in SSLepRmutant rats while not affecting SS rats. Overall, these data indicate that MIP3α plays an important role in renal inflammation during the early progression of renal injury in obese SSLepRmutant rats prior to puberty. These data also suggest that MIP3α may be a novel therapeutic target to inhibit insulin resistance and prevent progressive proteinuria in obese children. SIGNIFICANCE STATEMENT: Childhood obesity is increasing at an alarming rate and is now being associated with renal disease. Although most studies have focused on the mechanisms of renal injury associated with adult obesity, few studies have examined the mechanisms of renal injury involved during childhood obesity. In the current study, we observed that the progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant rats was associated with an increase in MIP3α, a chemokine, before puberty, and inhibition of MIP3α markedly reduced renal injury.
Collapse
Affiliation(s)
- Ubong S Ekperikpe
- Departments of Pharmacology and Toxicology and Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Bibek Poudel
- Departments of Pharmacology and Toxicology and Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Corbin A Shields
- Departments of Pharmacology and Toxicology and Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Sautan Mandal
- Departments of Pharmacology and Toxicology and Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Denise C Cornelius
- Departments of Pharmacology and Toxicology and Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Jan M Williams
- Departments of Pharmacology and Toxicology and Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| |
Collapse
|
|
11
|
Berkman ER, Richardson KL, Clark JD, Dick AAS, Lewis-Newby M, Diekema DS, Wightman AG. An ethical analysis of obesity as a contraindication of pediatric kidney transplant candidacy. Pediatr Nephrol 2023; 38:345-356. [PMID: 35488137 DOI: 10.1007/s00467-022-05572-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 01/10/2023]
Abstract
The inclusion of body mass index (BMI) as a criterion for determining kidney transplant candidacy in children raises clinical and ethical challenges. Childhood obesity is on the rise and common among children with kidney failure. In addition, obesity is reported as an independent risk factor for the development of CKD and kidney failure. Resultantly, more children with obesity are anticipated to need kidney transplants. Most transplant centers around the world use high BMI as a relative or absolute contraindication for kidney transplant. However, use of obesity as a relative or absolute contraindication for pediatric kidney transplant is controversial. Empirical data demonstrating poorer outcomes following kidney transplant in obese pediatric patients are limited. In addition, pediatric obesity is distributed inequitably among groups. Unlike adults, most children lack independent agency to choose their food sources and exercise opportunities; they are dependent on their families for these choices. In this paper, we define childhood obesity and review (1) the association and impact of obesity on kidney disease and kidney transplant, (2) existing adult guidelines and rationale for using high BMI as a criterion for kidney transplant, (3) the prevalence of childhood obesity among children with kidney failure, and (4) the existing literature on obesity and pediatric kidney transplant outcomes. We then discuss ethical considerations related to the use of obesity as a criterion for kidney transplant.
Collapse
Affiliation(s)
- Emily R Berkman
- Division of Pediatric Critical Care Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA.
- Division of Bioethics and Palliative Care Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA.
- Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA, USA.
| | - Kelsey L Richardson
- Division of Pediatric Nephrology, Oregon Health Sciences University, Portland, OR, USA
| | - Jonna D Clark
- Division of Pediatric Critical Care Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
- Division of Bioethics and Palliative Care Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
- Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA, USA
| | - André A S Dick
- Division of Transplantation, Section of Pediatric Transplantation, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
| | - Mithya Lewis-Newby
- Division of Bioethics and Palliative Care Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
- Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA, USA
- Division of Cardiac Critical Care, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
| | - Douglas S Diekema
- Division of Bioethics and Palliative Care Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
- Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA, USA
- Division of Pediatric Emergency Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
| | - Aaron G Wightman
- Division of Bioethics and Palliative Care Medicine, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
- Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA, USA
- Division of Pediatric Nephrology, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
| |
Collapse
|
|
12
|
Colasante AM, Bartiromo M, Nardolillo M, Guarino S, Marzuillo P, Mangoni di S Stefano GSRC, Miraglia del Giudice E, Di Sessa A. Tangled relationship between insulin resistance and microalbuminuria in children with obesity. World J Clin Pediatr 2022; 11:455-462. [PMID: 36439903 PMCID: PMC9685682 DOI: 10.5409/wjcp.v11.i6.455] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/19/2022] [Accepted: 10/27/2022] [Indexed: 11/07/2022] Open
Abstract
Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver, type 2 diabetes, metabolic syndrome, and cardiovascular disease. From a pathogenic point of view, insulin resistance (IR) represents the key factor underlying the spectrum of these obesity consequences. As observed in adults, recent data supported the occurrence of microalbuminuria (MA) as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity. In fact, a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics. Based on the clinical and prognostic relevance of this relationship in daily practice (including an increased risk of chronic kidney disease development overtime), more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity. In this paper, we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity: (1) What is the prevalence of pediatric MA? (2) What is the state of art of MA in children with obesity? and (3) Is there a link between IR and MA in children with obesity?
Collapse
Affiliation(s)
- Alberto Maria Colasante
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Mario Bartiromo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Michele Nardolillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | | | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| |
Collapse
|
|
13
|
Mazur A, Zachurzok A, Baran J, Dereń K, Łuszczki E, Weres A, Wyszyńska J, Dylczyk J, Szczudlik E, Drożdż D, Metelska P, Brzeziński M, Kozioł-Kozakowska A, Matusik P, Socha P, Olszanecka-Gilianowicz M, Jackowska T, Walczak M, Peregud-Pogorzelski J, Tomiak E, Wójcik M. Childhood Obesity: Position Statement of Polish Society of Pediatrics, Polish Society for Pediatric Obesity, Polish Society of Pediatric Endocrinology and Diabetes, the College of Family Physicians in Poland and Polish Association for Study on Obesity. Nutrients 2022; 14:nu14183806. [PMID: 36145182 PMCID: PMC9505061 DOI: 10.3390/nu14183806] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/05/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022] Open
Abstract
Childhood obesity is one of the most important problems of public health. Searching was conducted by using PubMed/MEDLINE, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases, from January 2022 to June 2022, for English language meta-analyses, systematic reviews, randomized clinical trials, and observational studies from all over the world. Five main topics were defined in a consensus join statement of the Polish Society of Pediatrics, Polish Society for Pediatric Obesity, Polish Society of Pediatric Endocrinology and Diabetes and Polish Association for the Study on Obesity: (1) definition, causes, consequences of obesity; (2) treatment of obesity; (3) obesity prevention; (4) the role of primary care in the prevention of obesity; (5) Recommendations for general practitioners, parents, teachers, and regional authorities. The statement outlines the role of diet, physical activity in the prevention and treatment of overweight and obesity, and gives appropriate recommendations for interventions by schools, parents, and primary health care. A multisite approach to weight control in children is recommended, taking into account the age, the severity of obesity, and the presence of obesity-related diseases. Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education are effective in improving metabolic and anthropometric indices. More actions are needed to strengthen the role of primary care in the effective prevention and treatment of obesity because a comprehensive, multi-component intervention appears to yield the best results.
Collapse
Affiliation(s)
- Artur Mazur
- Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszów, 35-310 Rzeszów, Poland
- Correspondence: (A.M.); (A.Z.); (M.W.)
| | - Agnieszka Zachurzok
- Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Zabrze, Poland
- Correspondence: (A.M.); (A.Z.); (M.W.)
| | - Joanna Baran
- Institute of Health Sciences, Medical College of Rzeszow University, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Katarzyna Dereń
- Institute of Health Sciences, Medical College of Rzeszow University, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Edyta Łuszczki
- Institute of Health Sciences, Medical College of Rzeszow University, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Aneta Weres
- Institute of Health Sciences, Medical College of Rzeszow University, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Justyna Wyszyńska
- Institute of Health Sciences, Medical College of Rzeszow University, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Justyna Dylczyk
- Children’s University Hospital, Jagiellonian University Medical College, 31-008 Kraków, Poland
| | - Ewa Szczudlik
- Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Pediatric Institute, Jagiellonian University Medical College, 31-008 Kraków, Poland
| | - Dorota Drożdż
- Department of Pediatric Nephrology and Hypertension, Chair of Pediatrics, Pediatric Institute, Jagiellonian University Medical College, 31-008 Kraków, Poland
| | - Paulina Metelska
- Department of Public Health and Social Medicine, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Michał Brzeziński
- Chair and Department of Paediatrics, Gastroenterology, Allergology and Child Nutrition, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Agnieszka Kozioł-Kozakowska
- Department of Pediatrics, Gastroenterology and Nutrition, Jagiellonian University Medical College, 31-008 Kraków, Poland
| | - Paweł Matusik
- Department of Pediatrics, Pediatric Obesity and Metabolic Bone Diseases, Chair of Pediatrics and Pediatric Endocrinology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland
| | - Piotr Socha
- The Children’s Memorial Health Institute, 04-736 Warsaw, Poland
| | - Magdalena Olszanecka-Gilianowicz
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical Faculty in Katowice, Medical University of Silesia, 40-055 Katowice, Poland
| | - Teresa Jackowska
- Department of Pediatrics, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Mieczysław Walczak
- Department of Pediatrics, Endocrinology, Diabetology, Metabolic Disorders and Cardiology of the Developmental Age, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Jarosław Peregud-Pogorzelski
- Department of Pediatrics, Pediatric Oncology and Immunology, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Elżbieta Tomiak
- The College of Family Physicians in Poland, 00-209 Warszawa, Poland
| | - Małgorzata Wójcik
- Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Pediatric Institute, Jagiellonian University Medical College, 31-008 Kraków, Poland
- Correspondence: (A.M.); (A.Z.); (M.W.)
| |
Collapse
|
|
14
|
Nair N, Kalra R, Chandra Bhatt G, Narang A, Kumar G, Raina R. The Effect and Prevalence of Comorbidities in Adolescents With CKD and Obesity. Adv Chronic Kidney Dis 2022; 29:251-262. [PMID: 36084972 DOI: 10.1053/j.ackd.2022.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/06/2022] [Accepted: 03/09/2022] [Indexed: 11/11/2022]
Abstract
Adolescent obesity and CKD are both significant public health issues independently. When seen as comorbid conditions, they can cause deleterious health outcomes that put them on the fast track to necessitate dialysis or transplantation. This paper analyzes the effects of various biomarkers and comorbidities seen in the intersection of obesity and CKD in the adolescent population. We illustrate the estimated prevalence of these biomarkers and comorbidities through a review of the literature, available treatment, and obesity-related glomerulopathies. We found significant prevalence of the biomarkers, microalbuminuria (9.42% ± 9.31% and interquartile range [IQR] of 9.5%), hypertension (23.60% ± 22.5% and IQR of 9.5%), low high-density lipoprotein (14.34% ± 5.46% and IQR of 5%), hyperfiltration (3.12% ± 5.16% and IQR of 4%), and lower estimated glomerular filtration rate 4.59 ± 2.75 and IQR of 3%. Identification of prevalent biomarkers and their manifestations can serve to inform clinicians what to look for in daily setting and help elucidate the magnitude of this growing issue. Additionally, pertinent treatment options from pharmacotherapy to bariatric surgery are outlined to provide care providers with the full spectrum of treatment options for obesity in adolescent populations.
Collapse
Affiliation(s)
- Nikhil Nair
- Department of Internal Medicine, Case Western Reserve University School of Medicine, Cleveland, OH
| | - Riti Kalra
- Department of Biology, Case Western Reserve University, Cleveland, OH
| | | | - Aarushi Narang
- Department of Pediatrics, ISN-SRC Pediatric Nephrology, All India Institute of Medical Sciences (AIIMS), Bhopal, India
| | - Gurinder Kumar
- Department of Pediatrics, The Metrohealth System, Cleveland, OH
| | - Rupesh Raina
- Department of Nephrology, Akron Children's Hospital, Akron, OH; Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH.
| |
Collapse
|
|
15
|
Poudel B, Shields CA, Ekperikpe US, Brown AK, Travis OK, Maury JC, Fitzgerald S, Smith SV, Cornelius DC, Williams JM. The SS LepR mutant rat represents a novel model to study obesity-induced renal injury before puberty. Am J Physiol Regul Integr Comp Physiol 2022; 322:R299-R308. [PMID: 35107024 PMCID: PMC8917907 DOI: 10.1152/ajpregu.00179.2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 01/26/2022] [Accepted: 01/26/2022] [Indexed: 02/08/2023]
Abstract
Prepubertal obesity (PPO) has emerged as a major health problem over the past few decades and is a risk factor for the development of proteinuria. The current study investigated whether the development of renal injury in the obese SSLepR mutant strain occurs before puberty. When determining the temporal changes in serum sex hormones in female and male SS and SSLepR mutant rats between 4 and 10 wk of age, we only observed significant increases in estradiol and testosterone levels in female and male SS rats at 10 wk of age than at 4 wk of age. The results suggest that studying both strains between 4 and 8 wk of age is appropriate to study the effects of PPO on renal injury in this model. Proteinuria was significantly higher in SSLepR mutant rats as opposed to the values observed in SS rats at 8 wk of age, and we did not observe any sex differences in proteinuria in either strain. The kidneys from the SSLepR mutant rats displayed significant glomerular and tubular injury and renal fibrosis versus the values measured in SS rats without any sex differences. Overall, we observed increased immune cell infiltration in the kidneys from SSLepR mutant rats compared with SS rats. Interestingly, female SSLepR mutant rats displayed significant increases in not only M1 macrophages (proinflammatory) but also M2 macrophages (anti-inflammatory) versus male SSLepR mutant rats. These results suggest the SSLepR mutant rat may be a useful model to study early progression of obesity-related renal injury before the onset of puberty.
Collapse
Affiliation(s)
- Bibek Poudel
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Corbin A Shields
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Ubong S Ekperikpe
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Andrea K Brown
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Olivia K Travis
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Jordan C Maury
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Sarah Fitzgerald
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Stanley V Smith
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Denise C Cornelius
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
- Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Jan M Williams
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| |
Collapse
|
|
16
|
Moreno JM, Martinez CM, de Jodar C, Reverte V, Bernabé A, Salazar FJ, Llinás MT. Gender differences in the renal changes induced by a prolonged high-fat diet in rats with altered renal development. J Physiol Biochem 2021; 77:431-441. [PMID: 33851366 DOI: 10.1007/s13105-021-00815-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 04/03/2021] [Indexed: 10/21/2022]
Abstract
The mechanisms involved in renal dysfunction induced by high-fat diet (HFD) in subjects with altered renal development (ARDev) are understudied. The objective of this study is to examine whether there are sex-dependent differences in the mechanisms involved in the hypertension and deterioration of renal function in SD rats with prolonged HFD and ARDev. The role of angiotensin II (Ang II) in the arterial pressure (AP) increments, the renal hemodynamic sensitivity to Ang II, glomerular damage and changes in fat abdominal volume, plasma adipokine levels, renal NADPHp67phox expression, and renal infiltration of immune cells were examined. Hypertension and deterioration of renal function were enhanced (P < 0.05) in both sexes of rats with HFD and ARDev. The decrease (P < 0.05) of AP elicited by candesartan in hypertensive rats was similar to that induced by the simultaneous administration of candesartan and apocynin. The greater (P < 0.05) renal vasoconstriction induced by Ang II in both sexes of rats with HFD and ARDev was accompanied by an enhanced (P < 0.05) infiltration of CD-3 cells and macrophages in the renal cortex and renal medulla. The increments (P < 0.05) in the renal expression of NADPHp67phox and glomeruloesclerosis were greater (P < 0.05) in males than in females with HFD and ARDev. Our results suggest that the hypertension and deterioration of renal function induced by HFD in rats with ARDev are Ang II-dependent and mediated by increments in oxidative stress and immune system activation. Sex-dependent increments in oxidative stress and glomerular damage may contribute to the deterioration of renal function in these rats.
Collapse
Affiliation(s)
- Juan M Moreno
- Department of Physiology, School of Medicine, University of Murcia, 30100, Murcia, Spain.,Biomedical Research Institute in Murcia, Murcia, Spain
| | | | - Carlos de Jodar
- Department of Pathology, School of Veterinary, University of Murcia, Murcia, Spain
| | - Virginia Reverte
- Department of Physiology, School of Medicine, University of Murcia, 30100, Murcia, Spain.,Biomedical Research Institute in Murcia, Murcia, Spain
| | - Antonio Bernabé
- Department of Pathology, School of Veterinary, University of Murcia, Murcia, Spain
| | - F Javier Salazar
- Department of Physiology, School of Medicine, University of Murcia, 30100, Murcia, Spain. .,Biomedical Research Institute in Murcia, Murcia, Spain.
| | - María T Llinás
- Department of Physiology, School of Medicine, University of Murcia, 30100, Murcia, Spain.,Biomedical Research Institute in Murcia, Murcia, Spain
| |
Collapse
|
|
17
|
di Palmo E, Filice E, Cavallo A, Caffarelli C, Maltoni G, Miniaci A, Ricci G, Pession A. Childhood Obesity and Respiratory Diseases: Which Link? CHILDREN (BASEL, SWITZERLAND) 2021; 8:177. [PMID: 33669035 PMCID: PMC7996509 DOI: 10.3390/children8030177] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/16/2021] [Accepted: 02/18/2021] [Indexed: 12/14/2022]
Abstract
Prevalence of childhood obesity is progressively increasing, reaching worldwide levels of 5.6% in girls and of 7.8% in boys. Several evidences showed that obesity is a major preventable risk factor and disease modifier of some respiratory conditions such as asthma and Obstructive Sleep Apnea Syndrome (OSAS). Co-occurrence of asthma and obesity may be due to common pathogenetic factors including exposure to air pollutants and tobacco smoking, Western diet, and low Vitamin D levels. Lung growth and dysanapsis phenomenon in asthmatic obese children play a role in impaired respiratory function which appears to be different than in adults. Genes involved in both asthma and obesity have been identified, though a gene-by-environment interaction has not been properly investigated yet. The identification of modifiable environmental factors influencing gene expression through epigenetic mechanisms may change the natural history of both diseases. Another important pediatric respiratory condition associated with obesity is Sleep-Disordered Breathing (SDB), especially Obstructive Sleep Apnea Syndrome (OSAS). OSAS and obesity are linked by a bidirectional causality, where the effects of one affect the other. The factors most involved in the association between OSAS and obesity are oxidative stress, systemic inflammation, and gut microbiota. In OSAS pathogenesis, obesity's role appears to be mainly due to mechanical factors leading to an increase of respiratory work at night-time. However, a causal link between obesity-related inflammatory state and OSAS pathogenesis still needs to be properly confirmed. To prevent obesity and its complications, family education and precocious lifestyle changes are critical. A healthy diet may lead to an improved quality of life in obese children suffering from respiratory diseases. The present review aimed to investigate the links between obesity, asthma and OSAS, focusing on the available evidence and looking for future research fields.
Collapse
Affiliation(s)
- Emanuela di Palmo
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.d.P.); (E.F.); (A.C.); (G.M.); (A.M.); (G.R.)
| | - Emanuele Filice
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.d.P.); (E.F.); (A.C.); (G.M.); (A.M.); (G.R.)
| | - Alessandra Cavallo
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.d.P.); (E.F.); (A.C.); (G.M.); (A.M.); (G.R.)
| | - Carlo Caffarelli
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy;
| | - Giulio Maltoni
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.d.P.); (E.F.); (A.C.); (G.M.); (A.M.); (G.R.)
| | - Angela Miniaci
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.d.P.); (E.F.); (A.C.); (G.M.); (A.M.); (G.R.)
| | - Giampaolo Ricci
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.d.P.); (E.F.); (A.C.); (G.M.); (A.M.); (G.R.)
| | - Andrea Pession
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.d.P.); (E.F.); (A.C.); (G.M.); (A.M.); (G.R.)
| |
Collapse
|
|
18
|
La Scola C, Guarino S, Pasini A, Capalbo D, Liguori L, Di Sessa A, Bertulli C, Mencarelli F, De Mutiis C, Campana G, La Manna A, Miraglia Del Giudice E, Pession A, Marzuillo P. Effect of Body Mass Index on Estimated Glomerular Filtration Rate Levels in Children With Congenital Solitary Kidney: A Cross-Sectional Multicenter Study. J Ren Nutr 2020; 30:261-267. [PMID: 31500951 DOI: 10.1053/j.jrn.2019.07.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 06/20/2019] [Accepted: 07/07/2019] [Indexed: 12/27/2022] Open
Abstract
RATIONALE & OBJECTIVE The objective of this study is to evaluate the effect of body mass index (BMI) on estimated glomerular filtration rate (eGFR) levels in children with congenital solitary kidney (CSK). Moreover, we evaluated if other factors could influence this relationship. STUDY DESIGN Multicenter cross-sectional study. SETTING & PARTICIPANTS University hospital pediatrics departments. SUBJECTS Two hundred eighty-one patients with CSK. PREDICTORS Weight, height, BMI-SDS (standard deviation score), duration of overweight/obesity, pubertal stage, systolic (SBP) and diastolic (DBP) blood pressure, eGFR, and renal ultrasound were obtained at the last follow-up visit. The population was classified on the basis of nutritional status and divided in tertiles for duration of overweight/obesity. We compared eGFR levels among these categories. A simple regression was used to correlate eGFR with BMI-SDS. To evaluate if other factors could influence the relationship between eGFR and BMI-SDS, a general linear model was performed, including gender, birth weight<2.5 kg, age, BMI-SDS, SBP-SDS, DBP-SDS, RL-SDS (renal length), and presence of kidney injury at last follow-up as covariates. RESULTS The eGFR levels reduced gradually from underweight to obese patients (P = .047). The eGFR levels significantly increased across first and second tertiles of duration of overweight/obesity while they decreased across second and third tertiles of duration of overweight/obesity (P = .005). The eGFR and BMI-SDS at last follow-up were indirectly correlated (coefficient = -0.30, r2 = 9.2%, P = .0004). A general linear model for eGFR variance (model R2 = 26.37%; P = .02) confirmed an indirect and significant association of eGFR values with BMI-SDS as the only significant finding. CONCLUSIONS In patients with CSK, the higher the BMI-SDS and the duration of overweight/obesity, the lower the eGFR levels. Primary prevention strategies to counteract overweight/obesity are mandatory in CSK patients.
Collapse
Affiliation(s)
- Claudio La Scola
- Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliero Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Stefano Guarino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Andrea Pasini
- Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliero Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Daniela Capalbo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Laura Liguori
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Cristina Bertulli
- Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliero Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Francesca Mencarelli
- Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliero Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Chiara De Mutiis
- Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliero Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Giuseppina Campana
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Angela La Manna
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Andrea Pession
- Pediatric Unit, Department of Woman, Child and Urologic Diseases, University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy.
| |
Collapse
|
|
19
|
Arora S, Dunkley L, Waldman LM, Chin VL, Umpaichitra V. Kidney function in minority children and adolescents with metabolically healthy and unhealthy obesity. Clin Obes 2020; 10:e12345. [PMID: 31692279 DOI: 10.1111/cob.12345] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 09/11/2019] [Accepted: 09/28/2019] [Indexed: 01/20/2023]
Abstract
Metabolic syndrome and/or body mass index (BMI) ≥40 kg/m2 are risk factors for kidney function decline in the general population. To compare creatinine (Cr), estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) between minority children and adolescents with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), a chart review was conducted on subjects aged 4 to 20 years with BMI ≥95th percentile from July 2014 to April 2017. They were stratified into MHO and MUO groups. Cr, eGFR and BUN were studied. Total n = 277: MHO n = 105 vs MUO n = 172. Cr was higher and BUN was lower in MUO whereas eGFR did not differ between the groups. Using general linear model, we found that metabolic status predicted BUN (P = .009) but not Cr or eGFR. When age, sex and Tanner stage matched, BUN, Cr and eGFR were similar between the groups. Higher BUN in MHO could be due to higher dietary protein intake. Subjects were divided into BMI ≥40 vs <40 kg/m2 , BUN and eGFR were not different. A trend towards higher Cr in those with BMI ≥40 kg/m2 (P = .054) was found; the group being older and taller. After age and height matching, all outcomes were not different. Higher Cr was found in those with elevated blood pressures vs the MHO (P = .047). Those with diastolic blood pressure (DBP) ≥90th percentile had higher Cr than those with systolic blood pressure ≥90th percentile (P = .017). Children and adolescents with MUO, and those with BMI ≥40 kg/m2 did not appear to have early diminished kidney function. Higher Cr, although in normal range, occurred in those with abnormal DBP.
Collapse
Affiliation(s)
- Sumeet Arora
- Pediatric Endocrinology Division, Department of Pediatrics, NYC Health + Hospitals/Kings County and SUNY Downstate Health Sciences University, Brooklyn, New York
| | - Laura Dunkley
- Department of Pediatrics, NYC Health + Hospitals/Kings County, Brooklyn, New York
| | - Lee M Waldman
- Department of Pediatrics, NYC Health + Hospitals/Kings County, Brooklyn, New York
| | - Vivian L Chin
- Pediatric Endocrinology Division, Department of Pediatrics, NYC Health + Hospitals/Kings County and SUNY Downstate Health Sciences University, Brooklyn, New York
| | - Vatcharapan Umpaichitra
- Pediatric Endocrinology Division, Department of Pediatrics, NYC Health + Hospitals/Kings County and SUNY Downstate Health Sciences University, Brooklyn, New York
| |
Collapse
|
|
20
|
Scudiero O, Pero R, Ranieri A, Terracciano D, Fimiani F, Cesaro A, Gentile L, Leggiero E, Laneri S, Moscarella E, Mazzaccara C, Frisso G, D'Alicandro G, Limongelli G, Pastore L, Calabrò P, Lombardo B. Childhood obesity: an overview of laboratory medicine, exercise and microbiome. Clin Chem Lab Med 2019; 58:1385-1406. [PMID: 31821163 DOI: 10.1515/cclm-2019-0789] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 11/12/2019] [Indexed: 12/17/2022]
Abstract
In the last few years, a significant increase of childhood obesity incidence unequally distributed within countries and population groups has been observed, thus representing an important public health problem associated with several health and social consequences. Obese children have more than a 50% probability of becoming obese adults, and to develop pathologies typical of obese adults, that include type 2-diabetes, dyslipidemia and hypertension. Also environmental factors, such as reduced physical activity and increased sedentary activities, may also result in increased caloric intake and/or decreased caloric expenditure. In the present review, we aimed to identify and describe a specific panel of parameters in order to evaluate and characterize the childhood obesity status useful in setting up a preventive diagnostic approach directed at improving health-related behaviors and identifying predisposing risk factors. An early identification of risk factors for childhood obesity could definitely help in setting up adequate and specific clinical treatments.
Collapse
Affiliation(s)
- Olga Scudiero
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Raffaela Pero
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy
| | - Annaluisa Ranieri
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Daniela Terracciano
- Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Naples "Federico II", Napoli, Italy
| | - Fabio Fimiani
- Divisione di Cardiologia, Dipartimento di Scienze Cardiotoraciche e Respiratorie, Università della Campania "Luigi Vanvitelli", Naples, Italy
| | - Arturo Cesaro
- Divisione di Cardiologia, Dipartimento di Scienze Cardiotoraciche e Respiratorie, Università della Campania "Luigi Vanvitelli", Naples, Italy
| | | | | | - Sonia Laneri
- Dipartimento di Farmacia, Università degli Studi di Naples "Federico II", Napoli, Italy
| | - Elisabetta Moscarella
- Dipartimento di Scienze Mediche Traslazionali, Università della Campania "Luigi Vanvitelli", Caserta, Italy.,Unità di Cardiologia, Ospedale "Sant'Anna e San Sebastiano", Caserta, Italy
| | - Cristina Mazzaccara
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Giulia Frisso
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Giovanni D'Alicandro
- Centro di Medicina dello Sport e delle Disabilità, Dipartimento di Neuroscienze e Riabilitazione, AORN, Santobono-Pausillipon, Naples, Italy
| | - Giuseppe Limongelli
- Dipartimento di Scienze Mediche Traslazionali, Università della Campania "Luigi Vanvitelli", Caserta, Italy
| | - Lucio Pastore
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Paolo Calabrò
- Dipartimento di Scienze Mediche Traslazionali, Università della Campania "Luigi Vanvitelli", Caserta, Italy.,Unità di Cardiologia, Ospedale "Sant'Anna e San Sebastiano", Caserta, Italy
| | - Barbara Lombardo
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| |
Collapse
|
|
21
|
Jadresic L, Silverwood RJ, Kinra S, Nitsch D. Can childhood obesity influence later chronic kidney disease? Pediatr Nephrol 2019; 34:2457-2477. [PMID: 30415420 DOI: 10.1007/s00467-018-4108-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 08/22/2018] [Accepted: 09/28/2018] [Indexed: 11/24/2022]
Abstract
Childhood overweight and obesity affects more and more children. Whilst associations of childhood overweight with later outcomes such as hypertension, diabetes and cardiovascular disease have been well documented, less is known about the association of childhood overweight and obesity with kidney disease. We review the existing evidence for the association of childhood obesity with markers of childhood and adult kidney disease. Whilst there is some evidence for an association, studies have not been able to distinguish between childhood being a sensitive time to develop later kidney problems, or whether observed associations of childhood obesity with poor outcomes are driven by greater lifelong exposure to obesity.
Collapse
Affiliation(s)
- Lyda Jadresic
- Department of Paediatrics, Gloucestershire Royal Hospital, Gloucester, GL1 3NN, UK
| | - Richard J Silverwood
- Department of Medical Statistics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Sanjay Kinra
- Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
| | - Dorothea Nitsch
- Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
| |
Collapse
|
|
22
|
Moreno JM, Tapia A, Martinez CM, Reverte V, Oltra L, Llinas MT, Salazar FJ. Sex-dependent differences in the adverse renal changes induced by an early in life exposure to a high-fat diet. Am J Physiol Renal Physiol 2018; 316:F332-F340. [PMID: 30516421 DOI: 10.1152/ajprenal.00394.2018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
This study examines whether the intake of a high-fat diet very early in life leads to changes in arterial pressure and renal function and evaluates whether the mechanisms involved in these changes are sex-dependent. Experiments were performed in male and female Sprague-Dawley rats fed a normal or high-fat diet from weaning to 4 mo of age. This exposure to a high-fat diet lead to an angiotensin II-dependent elevation in arterial pressure and to significant increments in fat abdominal volume and plasma leptin that were similar in both sexes. In addition, the angiotensin II-induced increment in renal vascular resistance was greater ( P < 0.05) in male (106 ± 14%) and female (97 ± 15%) rats fed a high-fat diet than in rats fed a normal-fat diet (51 ± 8%). However, the high-fat intake during early life induced increments in albuminuria, interleukin-6, and infiltration of CD3 lymphocytes in the renal parenchyma that were greater ( P < 0.05) in male than in female rats. Other sex-dependent differences in response to high-fat intake were that adiponectin levels only decreased in females (21%, P < 0.05), and renal NF-κB expression only increased in males (31%, P < 0.05). In summary, the early exposure to a high-fat diet leads to angiotensin II-dependent arterial pressure elevations and to increments in abdominal fat and in the renal sensitivity to angiotensin II that are similar in both sexes. However, the mechanisms involved in the renal changes associated with early exposure to a high-fat diet are different in males and females.
Collapse
Affiliation(s)
- Juan M Moreno
- Department of Physiology, School of Medicine, University of Murcia and Biomedical Research Institute of Murcia , Murcia , Spain
| | - Antonio Tapia
- Department of Physiology, School of Medicine, University of Murcia and Biomedical Research Institute of Murcia , Murcia , Spain
| | - Carlos M Martinez
- Pathology Unit, Biomedical Research Institute of Murcia , Murcia , Spain
| | - Virginia Reverte
- Department of Physiology, School of Medicine, University of Murcia and Biomedical Research Institute of Murcia , Murcia , Spain
| | - Lidia Oltra
- Department of Physiology, School of Medicine, University of Murcia and Biomedical Research Institute of Murcia , Murcia , Spain
| | - Maria Teresa Llinas
- Department of Physiology, School of Medicine, University of Murcia and Biomedical Research Institute of Murcia , Murcia , Spain
| | - Francisco Javier Salazar
- Department of Physiology, School of Medicine, University of Murcia and Biomedical Research Institute of Murcia , Murcia , Spain
| |
Collapse
|
|
23
|
Marzuillo P, Grandone A, Di Sessa A, Guarino S, Diplomatico M, Umano GR, Polito C, La Manna A, Perrone L, Miraglia Del Giudice E. Anthropometric and Biochemical Determinants of Estimated Glomerular Filtration Rate in a Large Cohort of Obese Children. J Ren Nutr 2018; 28:359-362. [PMID: 29452889 DOI: 10.1053/j.jrn.2018.01.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 01/05/2018] [Accepted: 01/06/2018] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE We aimed to investigate which clinical and metabolic factors could influence the estimated glomerular filtration rate (eGFR) levels, evaluating a large population of obese children without suspect of primary kidney disease. DESIGN Retrospective, cross-sectional study. SETTING Pediatric university department. SUBJECTS We enrolled 2,957 obese children and adolescents consecutively attending our department between January 2000 and 2017. Inclusion criteria were body mass index (BMI) > 95th percentile and eGFR > 90 mL/min/1.73 m2. Exclusion criteria were secondary forms of obesity, eGFR < 90 mL/min/1.73 m2, proteinuria/hematuria at urine dipstick, or consumption of any medication. INTERVENTIONS Weight, waist circumference, height, waist to height ratio (W/Hr), BMI-standard deviation score (SDS), pubertal stage, systolic blood pressure (SBP) and diastolic blood pressure (DBP), duration of obesity, insulin, eGFR, and homeostasis model assessment (HOMA-IR) were obtained. A general linear model was performed for a multiple variable analysis. MAIN OUTCOME MEASURE The population was divided in tertiles for BMI-SDS, W/Hr, SBP- and DBP-SDS, HOMA-IR, and duration of obesity. We compared eGFR levels among these tertiles. RESULTS The eGFR levels significantly increased across both BMI-SDS and W/Hr tertiles. Conversely the eGFR levels significantly decreased across SBP-SDS, HOMA-IR, and duration of obesity tertiles. No significant differences in eGFR levels across DBP-SDS tertiles were detected. Pubertal patients presented significantly lower eGFR values compared with prepubertal patients. A general linear model for eGFR variance including as covariates W/Hr, HOMA-IR, duration of obesity, pubertal stage, BMI-SDS, and SBP-SDS (model R2 39.7%; model P < .00001) was performed. It confirmed a direct association of eGFR values with BMI-SDS and an indirect association with HOMA-IR, duration of obesity, pubertal stage, and SBP-SDS. CONCLUSIONS We showed a positive correlation of eGFR with both BMI-SDS and a negative one with SBP-SDS, HOMA-IR, pubertal stage, and duration of obesity. The duration of obesity was the variable most significantly associated to eGFR levels.
Collapse
Affiliation(s)
- Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy.
| | - Anna Grandone
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Stefano Guarino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Mario Diplomatico
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Cesare Polito
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Angela La Manna
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Laura Perrone
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| |
Collapse
|
|
24
|
Valerio G, Maffeis C, Saggese G, Ambruzzi MA, Balsamo A, Bellone S, Bergamini M, Bernasconi S, Bona G, Calcaterra V, Canali T, Caroli M, Chiarelli F, Corciulo N, Crinò A, Di Bonito P, Di Pietrantonio V, Di Pietro M, Di Sessa A, Diamanti A, Doria M, Fintini D, Franceschi R, Franzese A, Giussani M, Grugni G, Iafusco D, Iughetti L, Lamborghini A, Licenziati MR, Limauro R, Maltoni G, Manco M, Reggiani LM, Marcovecchio L, Marsciani A, del Giudice EM, Morandi A, Morino G, Moro B, Nobili V, Perrone L, Picca M, Pietrobelli A, Privitera F, Purromuto S, Ragusa L, Ricotti R, Santamaria F, Sartori C, Stilli S, Street ME, Tanas R, Trifiró G, Umano GR, Vania A, Verduci E, Zito E. Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Ital J Pediatr 2018; 44:88. [PMID: 30064525 PMCID: PMC6069785 DOI: 10.1186/s13052-018-0525-6] [Citation(s) in RCA: 140] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 06/07/2018] [Indexed: 01/06/2023] Open
Abstract
The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.
Collapse
Affiliation(s)
- Giuliana Valerio
- Department of Movement Sciences and Wellbeing, University of Naples Parthenope, via Medina 40, 80133 Naples, Italy
| | - Claudio Maffeis
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - Giuseppe Saggese
- Department of Pediatrics, University Hospital of Pisa, Pisa, Italy
| | | | - Antonio Balsamo
- Department of Medical and Surgical Sciences, University Hospital S.Orsola-Malpighi, Bologna, Italy
| | - Simonetta Bellone
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | | | - Sergio Bernasconi
- Italian Society for Pediatric Endocrinology and Diabetology (SIEDP), Parma, Italy
| | - Gianni Bona
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Valeria Calcaterra
- Pediatrics Unit, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Margherita Caroli
- Italian Society for Obesity (SIO), Francavilla Fontana (Brindisi), Italy
| | | | - Nicola Corciulo
- Pediatric Unit, Hospital of Gallipoli, Gallipoli (Lecce), Italy
| | - Antonino Crinò
- Autoimmune Endocrine Diseases Unit, Bambino Gesù Children Hospital, IRCCS, Rome, Italy
| | - Procolo Di Bonito
- Department of Internal Medicine, “S. Maria delle Grazie”, Pozzuoli Hospital, Naples, Italy
| | | | - Mario Di Pietro
- Pediatric and Neonatal Unit, “G. Mazzini”Hospital, Teramo, Italy
| | - Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Antonella Diamanti
- Artificial Nutrition Unit Bambino Gesù, Children’s Hospital, IRCCS, Rome, Italy
| | - Mattia Doria
- Italian Federation of Pediatricians (FIMP), Venice, Italy
| | - Danilo Fintini
- Endocrinology and Diabetology Unit Bambino Gesù Children Hospital, IRCCS, Rome, Italy
| | | | - Adriana Franzese
- Department of Translational Medical Science, Regional Center for Pediatric Diabetes, University Federico II of Naples, Naples, Italy
| | | | - Graziano Grugni
- Division of Auxology, Istituto Auxologico Italiano, IRCCS, Verbania, Italy
| | - Dario Iafusco
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Lorenzo Iughetti
- Pediatric Unit, University of Modena and Reggio Emilia, Modena, Italy
| | | | | | | | - Giulio Maltoni
- Department of Medical and Surgical Sciences, University Hospital S.Orsola-Malpighi, Bologna, Italy
| | - Melania Manco
- Research Area for Multifactorial Diseases, Children’s Hospital Bambino Gesù, Rome, Italy
| | | | | | | | - Emanuele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Anita Morandi
- Pediatric Diabetes and Metabolic Disorders Unit, University Hospital of Verona, Verona, Italy
| | - Giuseppe Morino
- Nutrition Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | | | - Valerio Nobili
- Department of Pediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy
- Hepatometabolic Unit, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy
| | - Laura Perrone
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | | | | | | | | | | | - Roberta Ricotti
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Francesca Santamaria
- Department of Translational Medical Science, Regional Center for Pediatric Diabetes, University Federico II of Naples, Naples, Italy
| | - Chiara Sartori
- Department of Obstetrics, Gynaecology and Paediatrics, Arcispedale S.Maria Nuova-IRCCS, Reggio Emilia, Italy
| | | | - Maria Elisabeth Street
- Department of Obstetrics, Gynaecology and Paediatrics, Arcispedale S.Maria Nuova-IRCCS, Reggio Emilia, Italy
| | - Rita Tanas
- Italian Society for Pediatric Endocrinology and Diabetology (SIEDP), Ferrara, Italy
| | | | - Giuseppina Rosaria Umano
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Andrea Vania
- Department of Pediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy
| | - Elvira Verduci
- Deparment of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy
| | - Eugenio Zito
- Department of Social Sciences, University of Naples Federico II, Naples, Italy
| |
Collapse
|
|
25
|
Ricotti R, Genoni G, Giglione E, Monzani A, Nugnes M, Zanetta S, Castagno M, Marolda A, Bellomo G, Bona G, Bellone S, Prodam F. High-normal estimated glomerular filtration rate and hyperuricemia positively correlate with metabolic impairment in pediatric obese patients. PLoS One 2018; 13:e0193755. [PMID: 29505614 PMCID: PMC5837119 DOI: 10.1371/journal.pone.0193755] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 02/17/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Childhood obesity represents a major health concern worldwide due to its well established detrimental effect on cardiovascular and its potential negative effect on kidney functions. However, biomarkers that can help diagnose early stages of kidney damage in obese children represent an unmet clinical need. OBJECTIVES In this study, we asked whether the prevalence of microalbuminuria, estimated glomerular filtration rate (eGFR) or hyperuricemia recorded in a wide cohort of obese children and adolescents would positively correlate with cardiometabolic dysfunction in these subjects. METHODS We carried out a cross-sectional study on 360 obese children and adolescents between the ages of 3-18 years, enrolled in a tertiary care center. Clinical and biochemical evaluations including oral glucose tolerance tests (OGTTs) were performed on all patients. Microalbuminuria was defined as urinary albumin-to-creatinine ratio (u-ACR) of 30-300 mg/g. All data are expressed as mean ± standard deviation (SD), absolute values or percentages. Sex age-specific and eGFR SDs were used for statistical analyses. Serum uric acid ≥ 5.5 mg/dL was considered abnormal. RESULTS The prevalence of microalbuminuria was 6.4%. Except for a lower insulinogenic-index, no correlations between microalbuminuria and cardiometabolic risk factors were detected. eGFR was < -1 SD and > 1 SD in 1.4% and 60.8% of subjects, respectively. Subjects with an eGFR > 1 SD had higher systolic blood pressure, liver enzymes, insulin resistance, glucose and insulin during OGTT, lower insulin sensitivity and a more prevalent microalbuminuria. Hyperuricemia (27.5%) increased the odds of hypertension, HDL ≤ 10th percentile and glucose ≥ 155.0 mg/dL after 60 minutes of OGTT. CONCLUSIONS A worse cardiometabolic profile was observed in subjects with an eGFR > 1 SD compared to other subgroups. Therefore, pediatric obese patients with eGFR > 1 SD or hyperuricemia should be closely monitored for microalbuminuria and post-challenge glucose and insulin secretion, all potential indicators of renal dysfunction in these young patients.
Collapse
Affiliation(s)
- Roberta Ricotti
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Giulia Genoni
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Enza Giglione
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Alice Monzani
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Martina Nugnes
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Sara Zanetta
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Matteo Castagno
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Agostina Marolda
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Giorgio Bellomo
- Clinical Chemistry, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Gianni Bona
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Simonetta Bellone
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
- Interdisciplinary Research Center of Autoimmune Diseases (IRCAD) University of Eastern Piedmont, Novara, Italy
| | - Flavia Prodam
- SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
- Interdisciplinary Research Center of Autoimmune Diseases (IRCAD) University of Eastern Piedmont, Novara, Italy
- Endocrinology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
| |
Collapse
|
|
26
|
Schuh DS, Piccoli ÂB, Paiani RL, Maciel CR, Pellanda LC, Vilela MA. Ocular Signs Related to Overweight and Arterial Hypertension in Children: A Systematic Review. Open Ophthalmol J 2017; 11:273-285. [PMID: 29081867 PMCID: PMC5633707 DOI: 10.2174/1874364101711010273] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 05/20/2017] [Accepted: 06/18/2017] [Indexed: 12/18/2022] Open
Abstract
Background: The ocular effects of obesity and hypertension need to be established and can be used as prognostic markers. Objective: To estimate the prevalence of ophthalmological alterations in children and adolescents who are overweight and/or have SAH. Methods: The database for this study included all observational studies (CS, cohort, case-control and “baseline” description of randomized clinical trials) with children and/or adolescents who were overweight, obese or had SAH and that measured ophthalmological alterations. Results: Comparative studies with healthy children demonstrated positive association between body adiposity with retinal venular dilation, and SAH with retinal arteriolar narrowing. Different retinal fundus cameras and computer-assisted programs to evaluate the retinal vessels, variations in the methods of analysis, adjustments, populations, were the main arguments against formal meta-analysis. The heterogeneity was too high (I2 >90%, in fixed or randomized effects), and the lack of linearity, normal distribution and homoscedasticity did not recommend meta-regression. Conclusion: Obesity and SAH show associations with ophthalmological alterations, especially with retinal vessel diameter. Lack of standardization does not allow a quantitative evaluation.
Collapse
Affiliation(s)
- Daniela S Schuh
- Instituto de Cardiologia/Fundacao Universitária de Cardiologia, Porto Alegre, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Ângela B Piccoli
- Instituto de Cardiologia/Fundacao Universitária de Cardiologia, Porto Alegre, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Raquel L Paiani
- Instituto de Cardiologia/Fundacao Universitária de Cardiologia, Porto Alegre, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Cristiane R Maciel
- Instituto de Cardiologia/Fundacao Universitária de Cardiologia, Porto Alegre, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Lucia C Pellanda
- Instituto de Cardiologia/Fundacao Universitária de Cardiologia, Porto Alegre, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Manuel Ap Vilela
- Instituto de Cardiologia/Fundacao Universitária de Cardiologia, Porto Alegre, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| |
Collapse
|
|
27
|
Morato M, Correia-Costa L, Sousa T, Cosme D, Schaefer F, Areias JC, Guerra A, Afonso AC, Barros H, Azevedo A, Albino-Teixeira A. Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children. Pediatr Nephrol 2017; 32:1411-1422. [PMID: 28337615 DOI: 10.1007/s00467-017-3639-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 02/27/2017] [Accepted: 02/27/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association. METHODS Cross-sectional evaluation of 305 children aged 8-9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay. RESULTS U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT. CONCLUSIONS A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin-angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.
Collapse
Affiliation(s)
- Manuela Morato
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal.
- Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy of the University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
- MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of University of Porto, Porto, Portugal.
| | - Liane Correia-Costa
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
- Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
- Department of Pediatrics, Faculty of Medicine of University of Porto, Porto, Portugal
| | - Teresa Sousa
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal
- MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
| | - Dina Cosme
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
| | - Franz Schaefer
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
| | - José Carlos Areias
- Division of Pediatric Cardiology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - António Guerra
- Department of Pediatrics, Faculty of Medicine of University of Porto, Porto, Portugal
- Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
- CINTESIS - Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Alberto Caldas Afonso
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
- Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
- Department of Pediatrics, Faculty of Medicine of University of Porto, Porto, Portugal
| | - Henrique Barros
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
- Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Porto, Portugal
| | - Ana Azevedo
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
- Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Porto, Portugal
| | - António Albino-Teixeira
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal
- MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
| |
Collapse
|
|
28
|
Gallibois CM, Jawa NA, Noone DG. Hypertension in pediatric patients with chronic kidney disease: management challenges. Int J Nephrol Renovasc Dis 2017; 10:205-213. [PMID: 28794651 PMCID: PMC5538700 DOI: 10.2147/ijnrd.s100891] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem.
Collapse
Affiliation(s)
- Claire M Gallibois
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada
- Faculty of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Natasha A Jawa
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Damien G Noone
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada
| |
Collapse
|
|
29
|
Chowdhury SS, Lecomte V, Erlich JH, Maloney CA, Morris MJ. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring. Nutrients 2016; 8:E521. [PMID: 27563922 PMCID: PMC5037508 DOI: 10.3390/nu8090521] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 08/16/2016] [Accepted: 08/17/2016] [Indexed: 12/28/2022] Open
Abstract
Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.
Collapse
Affiliation(s)
- Sabiha S Chowdhury
- School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia.
| | - Virginie Lecomte
- School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia.
| | - Jonathan H Erlich
- Prince of Wales Clinical School, University of New South Wales, Sydney 2052, NSW, Australia.
- Department of Nephrology, Prince of Wales Hospital, Randwick 2031, NSW, Australia.
| | - Christopher A Maloney
- School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia.
| | - Margaret J Morris
- School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia.
| |
Collapse
|
|
30
|
Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function. Br J Nutr 2016; 116:805-15. [PMID: 27480380 DOI: 10.1017/s0007114516002804] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.
Collapse
|
|
31
|
Correia-Costa L, Schaefer F, Afonso AC, Bustorff M, Guimarães JT, Guerra A, Barros H, Azevedo A. Normalization of glomerular filtration rate in obese children. Pediatr Nephrol 2016; 31:1321-8. [PMID: 27008644 DOI: 10.1007/s00467-016-3367-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 03/03/2016] [Accepted: 03/04/2016] [Indexed: 10/22/2022]
Abstract
BACKGROUND Glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA), but this may lead to biased results when applied to subjects of abnormal body size. The aim of our study was to examine the impact of normalization to the BSA and alternative body size descriptors on measured and estimated GFR in overweight and obese children. METHODS This was a cross-sectional study of 313 children aged 8-9 years old. GFR was measured by 24-h creatinine clearance (CrCl) and additionally estimated from serum creatinine and cystatin C (CysC) using the combined Zappitelli formula, both as absolute values and adjusted to various body size descriptors. The results were compared between 163 normal-weight, 89 overweight and 61 obese children. RESULTS Compared to the normal-weight children, mean absolute GFR (both measured and estimated) was higher in the overweight and obese children, whereas BSA-adjusted GFR was lower. Linear regression models fitted in normal-weight children revealed equally close associations between absolute GFR and squared height, ideal body weight (IBW) and BSA derived from IBW. Normalization of GFR to the IBW-derived BSA completely eliminated the discrepancy between absolute and BSA-indexed GFR in overweight and obese children. CONCLUSIONS Indexing of GFR to BSA calculated from the ideal-rather than actual-body weight is a promising approach to avoid overcorrection when studying obese children. Further studies should assess the accuracy of this approach across the full range of age and BMI distribution.
Collapse
Affiliation(s)
- Liane Correia-Costa
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto (ISPUP), Rua das Taipas nr. 135, 4050-600, Porto, Portugal. .,Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal. .,Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Franz Schaefer
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
| | - Alberto Caldas Afonso
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto (ISPUP), Rua das Taipas nr. 135, 4050-600, Porto, Portugal.,Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal.,Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Manuela Bustorff
- Department of Nephrology, Centro Hospitalar São João, Porto, Portugal
| | - João Tiago Guimarães
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto (ISPUP), Rua das Taipas nr. 135, 4050-600, Porto, Portugal.,Department of Clinical Pathology , Centro Hospitalar São João, Porto, Portugal.,Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal
| | - António Guerra
- Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.,Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - Henrique Barros
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto (ISPUP), Rua das Taipas nr. 135, 4050-600, Porto, Portugal.,Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Ana Azevedo
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto (ISPUP), Rua das Taipas nr. 135, 4050-600, Porto, Portugal.,Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal
| |
Collapse
|
|
32
|
Arany I, Hall S, Reed DK, Dixit M. The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells. Mol Med Rep 2016; 14:2771-7. [PMID: 27486058 DOI: 10.3892/mmr.2016.5543] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Accepted: 07/14/2016] [Indexed: 11/05/2022] Open
Abstract
Nicotine (NIC) exposure augments free fatty acid (FFA) deposition and oxidative stress, with a concomitant increase in the expression of the pro-oxidant p66shc. In addition, a decrease in the antioxidant manganese superoxide dismutase (MnSOD) has been observed in the kidneys of mice fed a high‑fat diet. The present study aimed to determine whether the pro‑oxidant p66shc mediates NIC‑dependent increases in renal oxidative stress by augmenting the production of reactive oxygen species (ROS) and suppressing the FFA‑induced antioxidant response in cultured NRK52E renal proximal tubule cells. Briefly, NRK52E renal proximal tubule cells were treated with 200 µM NIC, 100 µM oleic acid (OA), or a combination of NIC and OA. The expression levels of p66shc and MnSOD were modulated according to genetic methods. ROS production and cell injury, in the form of lactate dehydrogenase release, were subsequently detected. Promoter activity of p66shc and MnSOD, as well as forkhead box (FOXO)‑dependent transcription, was investigated using reporter luciferase assays. The results demonstrated that NIC exacerbated OA‑mediated intracellular ROS production and cell injury through the transcriptional activation of p66shc. NIC also suppressed OA‑mediated induction of the antioxidant MnSOD promoter activity through p66shc‑dependent inactivation of FOXO activity. Overexpression of p66shc and knockdown of MnSOD had the same effect as treatment with NIC on OA‑mediated lipotoxicity. These data may be used to generate a therapeutic means to ameliorate renal lipotoxicity in obese smokers.
Collapse
Affiliation(s)
- Istvan Arany
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Samuel Hall
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Dustin K Reed
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Mehul Dixit
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA
| |
Collapse
|
|
33
|
Correia-Costa L, Morato M, Sousa T, Cosme D, Guimarães JT, Guerra A, Schaefer F, Afonso AC, Azevedo A, Albino-Teixeira A. Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children. Pediatr Nephrol 2016; 31:455-64. [PMID: 26482255 DOI: 10.1007/s00467-015-3232-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 09/27/2015] [Accepted: 09/28/2015] [Indexed: 01/14/2023]
Abstract
BACKGROUND Fibrogenic cytokines are recognized as putative drivers of disease activity and histopathological deterioration in various kidney diseases. We compared urinary transforming growth factor β1 (U-TGF-β1) and endothelin 1 (U-ET-1) levels across body mass index classes and assessed their association with the level of urinary angiotensinogen (U-AGT), a biomarker of intrarenal renin-angiotensin-aldosterone system (RAAS). METHODS The was a cross-sectional evaluation of 302 children aged 8-9 years. Ambulatory blood pressure (BP), insulin resistance (HOMA-IR), aldosterone level and renal function were evaluated. U-ET-1, U-TGF-β1 and U-AGT levels were determined by immunoenzymatic methods. RESULTS Obese children presented with the lowest levels of U-ET-1 and U-TGF-β1, but the difference was only significant for U-ET-1. In obese children, the median levels of both U-ET-1 and U-TGF-β1 tended to increase across tertiles (T1-T3) of U-AGT (U-ET-1: T1, 19.9 (14.2-26.3); T2, 32.5 (23.3-141.6); T3, 24.8 (18.7-51.5) ng/g creatinine, p = 0.007; U-TGF-β1: T1, 2.2 (1.8-4.0); T2, 4.3 (2.7-11.7); T3, 4.9 (3.8-10.1) ng/g creatinine, p = 0.004]. In multivariate models, in the obese group, U-ET-1 was associated with HOMA-IR and aldosterone and U-AGT levels, and U-TGF-β1 was associated with U-AGT levels and 24 h-systolic BP. CONCLUSIONS Whereas the initial hypothesis of higher levels of urinary fibrogenic cytokines in obese children was not confirmed in our study, both TGF-β1 and U-ET-1 levels were associated with U-AGT level, which likely reflects an early interplay between tissue remodeling and RAAS in obesity-related kidney injury.
Collapse
Affiliation(s)
- Liane Correia-Costa
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal.
- Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal.
- Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Manuela Morato
- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Teresa Sousa
- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal
| | - Dina Cosme
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal
- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - João Tiago Guimarães
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal
- Department of Clinical Pathology, Centro Hospitalar São João, Porto, Portugal
- Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal
| | - António Guerra
- Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal
- Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - Franz Schaefer
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
| | - Alberto Caldas Afonso
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal
- Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
- Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Ana Azevedo
- Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal
- Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal
| | - António Albino-Teixeira
- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal
| |
Collapse
|
|
34
|
Arany I, Hall S, Reed DK, Reed CT, Dixit M. Nicotine Enhances High-Fat Diet-Induced Oxidative Stress in the Kidney. Nicotine Tob Res 2016; 18:1628-34. [PMID: 26896163 DOI: 10.1093/ntr/ntw029] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 01/19/2016] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. Both smoking-through nicotine (NIC)-and obesity-by free fatty acid overload-provoke oxidative stress in the kidney, which ultimately results in development of chronic kidney injury. Their combined renal risk, however, is virtually unknown. We tested the hypothesis that chronic NIC exposure worsens renal oxidative stress in mice on high-fat diet (HFD) by altering the balance between expression of pro-oxidant and antioxidant genes. METHODS Nine-week-old male C57Bl/6J mice consumed normal diet (ND) or HFD and received either NIC (200 μg/ml) or vehicle (2% saccharine) in their drinking water. Body weight, plasma clinical parameters, renal lipid deposition, markers of renal oxidative stress and injury, as well as renal expression of the pro-oxidant p66shc and the antioxidant MnSOD were determined after 12 weeks. RESULTS NIC significantly augmented levels of circulating free fatty acid, as well as lipid deposition, oxidative stress and sublethal injury in the kidneys of mice on HFD. In addition, NIC exposure suppressed HFD-mediated induction of MnSOD while increased expression of p66shc in the kidney. CONCLUSIONS Tobacco smoking or the increasingly popular E-cigarettes-via NIC exposure-could worsen obesity-associated lipotoxicity in the kidney. Hence, our findings could help to develop strategies that mitigate adverse effects of NIC on the obese kidney. IMPLICATIONS Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. NIC-the main component of tobacco smoke, E-cigarettes and replacement therapies-links smoking to renal injury via oxidative stress, which could superimpose renal oxidative stress caused by obesity. Our results substantiate this scenario using a mouse model of diet induced obesity and NIC exposure and imply the augmented long-term renal risk in obese smokers. Also, our study may help to develop strategies that mitigate adverse effects of NIC on the obese kidney.
Collapse
Affiliation(s)
- Istvan Arany
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS;
| | - Samuel Hall
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS
| | - Dustin K Reed
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS
| | - Caitlyn T Reed
- Department of Pathology, University of Mississippi Medical Center, Jackson, MS
| | - Mehul Dixit
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS
| |
Collapse
|
|
35
|
Barnett M, Hall S, Dixit M, Arany I. Simvastatin attenuates oleic acid-induced oxidative stress through CREB-dependent induction of heme oxygenase-1 in renal proximal tubule cells. Pediatr Res 2016; 79:243-50. [PMID: 26492285 DOI: 10.1038/pr.2015.210] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 07/30/2015] [Indexed: 12/25/2022]
Abstract
BACKGROUND Statins elicit antioxidant effects independently of their lipid-lowering properties. Heme oxygenase-1 (HO-1) induction may be a part of these pleiotropic effects, which are insufficiently described in the kidney. We hypothesize that simvastatin (SIM) transcriptionally activates HO-1 that protects renal proximal tubule cells from lipotoxic injury. METHODS Impact of SIM on 100 μmol/l oleic acid (OA)-mediated reactive oxygen species (ROS) production and consequent oxidative stress (4-hydroxynonenal (HNE) content) as well as cell injury/apoptosis (lactate dehydrogenase (LDH) release, caspase-3 activation) were determined in cultured renal proximal tubule (NRK52E) cells. Effect of SIM on the HO-1 promoter and its enhancer elements (antioxidant response element (ARE), CCAAT, AP1, and cAMP response element (CRE)) was also determined in reporter luciferase assays. Dominant-negative (dnMEK, M1CREB) and pharmacologic (H89) approaches were used to inhibit activation of extracellular signal regulated kinase (ERK), CREB, and protein kinase A (PKA), respectively. RESULTS SIM dose-dependently activated the HO-1 promoter that was essential for protection against OA-dependent ROS production/oxidative stress and LDH release/caspase-3 activation. We found that the HO-1 promoter was induced through ERK and PKA-dependent activation of the CRE by SIM. CONCLUSION SIM may protect the kidney from adverse effects of circulating fatty acids by upregulating the antioxidant HO-1, aside from its well-described lipid-lowering effects.
Collapse
Affiliation(s)
- Meaghan Barnett
- Department of Pediatrics, Division of Critical Care, University of Mississippi Medical Center, Jackson, Mississippi
| | - Samuel Hall
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Mehul Dixit
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Istvan Arany
- Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, Mississippi
| |
Collapse
|
|
36
|
Persistent Albuminuria in Children with Type 2 Diabetes: A Canadian Paediatric Surveillance Program Study. J Pediatr 2016; 168:112-117. [PMID: 26470688 DOI: 10.1016/j.jpeds.2015.09.042] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Revised: 08/05/2015] [Accepted: 09/10/2015] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To determine the prevalence and the clinical features associated with persistent albuminuria in Canadian children aged <18 years with type 2 diabetes. STUDY DESIGN This national prospective surveillance study involved a network of pediatricians and pediatric endocrinologists. Cases of persistent albuminuria in children with type 2 diabetes were reported during a 24-month period from 2010 to 2012. Persistent albuminuria was defined as an elevated albumin-to-creatinine ratio in a minimum of 2 out of 3 urine samples obtained at least 1 month apart over 3-6 months and confirmed with a first morning sample. Descriptive statistics were used to illustrate demographic and clinical features of the population. The prevalence of persistent albumuria was estimated using data from a previous national surveillence study of type 2 diabetes in children. RESULTS Fifty cases were reported over the 24-month study period. The estimated prevalence of persistent albuminuria in children with type 2 diabetes in Canada was 5.1%. The median duration of diabetes at the time of diagnosis of albuminuria was 21 days (IQR, 0-241 days). Almost two-thirds (64%) were female, 80% were of Canadian First Nations heritage, and 76% were from Manitoba. Exposure to gestational or pregestational diabetes in utero occurred in 65%, and 48% had a family history of diabetes-related renal disease. Structural anomalies of the kidney were found in 37%. CONCLUSION Persistent albuminuria occurs in youths with type 2 diabetes in the first year after diagnosis, demonstrates regional variation, and is associated with First Nations heritage and exposure to maternal diabetes during pregnancy.
Collapse
|
|
37
|
Correia-Costa L, Sousa T, Morato M, Cosme D, Afonso J, Moura C, Mota C, Areias JC, Guerra A, Schaefer F, Caldas Afonso A, Barros H, Albino-Teixeira A, Azevedo A. Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children. Eur J Clin Invest 2016; 46:50-9. [PMID: 26541603 DOI: 10.1111/eci.12564] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 11/01/2015] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children. MATERIALS/METHODS Cross-sectional evaluation of 309 children aged 8-9 years (161 normal weight, 148 overweight/obese), members of the birth cohort Generation I (Portugal). Anthropometrics (body mass index (BMI), waist-to-height ratio (WHtR) and % body fat mass (%BFM) by bioelectrical impedance analysis), 24-h ambulatory blood pressure monitoring and pulse wave velocity (PWV) were measured. Insulin resistance was estimated by the HOMA index (considering serum fasting glucose and insulin determinations). Serum MPO levels were assessed by immunoenzymatic assay. RESULTS MPO levels were positively associated with obesity indices (BMI z-score, WHtR and %BFM). Higher MPO levels were associated with higher 24-h and night-time mean arterial pressure, with nondipping and with higher values of insulin resistance. In normal weight children, the endothelial function, as evaluated indirectly by PWV, was an independent predictor of MPO levels. In overweight/obese children, estimated glomerular filtration rate increased significantly across tertiles of MPO (Ptrend = 0·031) and this association held after adjustment for age, sex, neutrophil and monocyte counts and CV risk factors. CONCLUSIONS Our results reinforce the role of MPO as a risk marker in obesity and related CV morbidities in young children. MPO levels associate with the dipping pattern and PWV and, among overweight/obese children, an association exists between MPO and renal function.
Collapse
Affiliation(s)
- Liane Correia-Costa
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.,Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - Teresa Sousa
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal.,MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
| | - Manuela Morato
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal.,MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.,Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of Porto, REQUIMTE, University of Porto, Porto, Portugal
| | - Dina Cosme
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.,Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal
| | - Joana Afonso
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal
| | - Cláudia Moura
- Division of Pediatric Cardiology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - Cláudia Mota
- Division of Pediatric Cardiology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - José Carlos Areias
- Division of Pediatric Cardiology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - António Guerra
- Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - Franz Schaefer
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
| | - Alberto Caldas Afonso
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.,Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal
| | - Henrique Barros
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.,Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Porto, Portugal
| | - António Albino-Teixeira
- Department of Pharmacology and Therapeutics, Faculty of Medicine of University of Porto, Porto, Portugal.,MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
| | - Ana Azevedo
- EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal.,Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Porto, Portugal
| |
Collapse
|
|
38
|
Decreased renal function in overweight and obese prepubertal children. Pediatr Res 2015; 78:436-44. [PMID: 26151492 DOI: 10.1038/pr.2015.130] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 04/17/2015] [Indexed: 01/30/2023]
Abstract
BACKGROUND Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity.
Collapse
|
|
39
|
Zhao YL, Liu ZJ, Bai XM, Wang YC, Li GH, Yan XY. Obesity increases the risk of renal involvement in children with Henoch-Schönlein purpura. Eur J Pediatr 2015; 174:1357-63. [PMID: 25899072 DOI: 10.1007/s00431-015-2547-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Revised: 04/08/2015] [Accepted: 04/14/2015] [Indexed: 01/12/2023]
Abstract
UNLABELLED The main aim of this study was to evaluate the relationship between obesity and renal involvement in children with Henoch-Schönlein purpura (HSP). A retrospective study of 141 pediatric patients with HSP was conducted in our hospital. The clinical data of all patients were collected from the electronic medical record management system from January 2010 to June 2014. The possible risk factors of renal involvement, especially obesity, were analyzed using univariate and multivariate analyses. Renal involvement occurred in 45/141 of the patients. A univariate analysis showed that an age more than 7 years at onset, persistent purpura, obesity, time from symptoms onset to diagnosis more than 14 days, and decreased C3 all increased the risk of renal involvement in HSP. The forward stepwise logistic regression analysis indicated obesity (odds ratio (OR) 4.43, 95 % confidence interval (CI) 1.896 to 10.358), age more than 7 years at onset (OR 2.81, 95 % CI 1.142 to 6.907), and persistent purpura (OR 2.57, 95 % CI 1.119 to 5.909) were independent risk factors for renal involvement. CONCLUSIONS Our results show that obesity can increase the hazard of renal involvement in children with HSP and reconfirm that older age at onset and persistent purpura are the independent risk factors for renal involvement. WHAT IS KNOWN • There have been some reports that obesity was associated with the development of renal injury. • It is not clear whether obesity can increase the risk of renal involvement in children with HSP. What is New: • The main finding of this study is that obesity can increase the hazard of renal involvement in children with HSP.
Collapse
Affiliation(s)
- Yong-Li Zhao
- Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.
| | - Zheng-Juan Liu
- Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.
| | - Xue-Mei Bai
- Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.
| | - Yu-Chuan Wang
- Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.
| | - Guo-Hua Li
- Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.
| | - Xue-Yan Yan
- Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.
| |
Collapse
|
|
40
|
Kirejczyk JK, Korzeniecka-Kozerska A, Baran M, Porowska H, Porowski T, Wasilewska A. Dyslipidaemia in overweight children and adolescents is associated with an increased risk of kidney stones. Acta Paediatr 2015; 104:e407-13. [PMID: 26096629 DOI: 10.1111/apa.13079] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2015] [Revised: 05/03/2015] [Accepted: 06/09/2015] [Indexed: 01/08/2023]
Abstract
AIM There is conflicting evidence about the role of obesity in paediatric nephrolithiasis. This Polish study explored the influence of nutritional status and lipid disturbances on urinary lithogenic factors and the risk of kidney stone formation in children and adolescents from three to 18 years of age. METHODS We carried out serum lipid profile evaluations and 24-h urine chemistry analyses on 493 overweight/obese paediatric participants (mean age 13 years) without nephrolithiasis and 492 healthy normal weight sex and age-matched controls. RESULTS A third (33%) of the study group had blood lipid disturbances, with more acidic urine, lower urinary citrate excretion and a higher fraction of ionised calcium and higher Bonn Risk Index than the controls. The participants' body mass index standard deviation score (BMI Z-score) was positively correlated with urinary oxalate and uric acid and negatively correlated with citrate excretion. Total cholesterol, low-density lipoprotein cholesterol and triglycerides correlated negatively with citraturia, while high-density lipoprotein cholesterol correlated positively. CONCLUSION The main factor that predisposed overweight and obese children to kidney stones was hypocitraturia. Urinary citrate excretion was related to both BMI Z-scores and all lipid fraction abnormalities. However, hypercholesterolaemia and particularly low-density lipoprotein hypercholesterolaemia seemed to play a major role.
Collapse
Affiliation(s)
- J K Kirejczyk
- Department of Paediatric Surgery; Medical University of Bialystok; Bialystok Poland
| | - A Korzeniecka-Kozerska
- Department of Paediatrics and Nephrology; Medical University of Bialystok; Bialystok Poland
| | - M Baran
- Department of Paediatrics, Endocrinology; Diabetology with Cardiology Division; Medical University of Bialystok; Bialystok Poland
| | - H Porowska
- Department of Medical Chemistry; Medical University of Bialystok; Bialystok Poland
| | - T Porowski
- Department of Paediatrics and Nephrology; Medical University of Bialystok; Bialystok Poland
| | - A Wasilewska
- Department of Paediatrics and Nephrology; Medical University of Bialystok; Bialystok Poland
| |
Collapse
|
|
41
|
Franchini S, Savino A, Marcovecchio ML, Tumini S, Chiarelli F, Mohn A. The effect of obesity and type 1 diabetes on renal function in children and adolescents. Pediatr Diabetes 2015; 16:427-33. [PMID: 25131409 DOI: 10.1111/pedi.12196] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2014] [Revised: 06/11/2014] [Accepted: 06/25/2014] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Early signs of renal complications can be common in youths with type 1 diabetes (T1D). Recently, there has been an increasing interest in potential renal complications associated with obesity, paralleling the epidemics of this condition, although there are limited data in children. HYPOTHESIS Obese children and adolescents present signs of early alterations in renal function similar to non-obese peers with T1D. SUBJECTS Eighty-three obese (age: 11.6 ± 3.0 yr), 164 non-obese T1D (age: 12.4 ± 3.2 yr), and 71 non-obese control (age: 12.3 ± 3.2 yr) children and adolescents were enrolled in the study. METHODS Anthropometric parameters and blood pressure were measured. Renal function was assessed by albumin excretion rate (AER), serum cystatin C, creatinine and estimated glomerular filtration rate (e-GFR), calculated using the Bouvet's formula. RESULTS Obese and non-obese T1D youths had similar AER [8.9(5.9-10.8) vs. 8.7(5.9-13.1) µg/min] and e-GFR levels (114.8 ± 19.6 vs. 113.4 ± 19.1 mL/min), which were higher than in controls [AER: 8.1(5.9-8.7) µg/min, e-GFR: 104.7 ± 18.9 mL/min]. Prevalence of microalbuminuria and hyperfiltration was similar between obese and T1D youths and higher than their control peers (6.0 vs. 8.0 vs. 0%, p = 0.02; 15.9 vs. 15.9 vs. 4.3%, p = 0.03, respectively). Body mass index (BMI) z-score was independently related to e-GFR (r = 0.328; p < 0.001), and AER (r = 0.138; p = 0.017). Hemoglobin A1c (HbA1c) correlated with AER (r = 0.148; p = 0.007) but not with eGFR (r = 0.041; p = 0.310). CONCLUSIONS Obese children and adolescents show early alterations in renal function, compared to normal weight peers, and they have similar renal profiles than age-matched peers with T1D.
Collapse
Affiliation(s)
| | | | - M Loredana Marcovecchio
- Department of Pediatrics, University of Chieti, Chieti, Italy.,Clinical Research Centre, Center of Excellence on Aging, 'G. D'Annunzio' University Foundation, University of Chieti, Chieti, Italy
| | - Stefano Tumini
- Department of Pediatrics, University of Chieti, Chieti, Italy
| | - Francesco Chiarelli
- Department of Pediatrics, University of Chieti, Chieti, Italy.,Clinical Research Centre, Center of Excellence on Aging, 'G. D'Annunzio' University Foundation, University of Chieti, Chieti, Italy
| | - Angelika Mohn
- Department of Pediatrics, University of Chieti, Chieti, Italy.,Clinical Research Centre, Center of Excellence on Aging, 'G. D'Annunzio' University Foundation, University of Chieti, Chieti, Italy
| |
Collapse
|
|
42
|
Xiao N, Devarajan P, Inge TH, Jenkins TM, Bennett M, Mitsnefes MM. Subclinical kidney injury before and 1 year after bariatric surgery among adolescents with severe obesity. Obesity (Silver Spring) 2015; 23:1234-8. [PMID: 25959555 PMCID: PMC4446189 DOI: 10.1002/oby.21070] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 02/11/2015] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To assess subclinical kidney injury in adolescents with severe obesity by measuring biomarkers of early kidney disease and to assess changes in the levels of these biomarkers following bariatric procedures. METHODS Twenty-two adolescents undergoing bariatric surgery with no microalbuminuria and normal kidney function were selected. Urinary NGAL, IL-18, and KIM-1 were measured at baseline, 6 and 12 months postoperatively. Biomarker levels were compared to 44 age-gender-matched lean controls. RESULTS Subjects with obesity had a mean baseline BMI of 48 kg/m(2) that decreased by 34% at 1-year follow-up. Urine NGAL, IL-18, and KIM-1 were significantly elevated in subjects with obesity compared to lean controls at baseline. The obese cohort had a further significant increase in NGAL and KIM-1 at 6 months, followed by decline at 1 year. The overall change in levels of all three biomarkers through 1 year after surgery, however, was not significant compared to baseline. CONCLUSIONS Adolescent severe obesity is associated with increased urinary excretion of novel biomarkers of kidney injury, despite no microalbuminuria or decreased kidney function. This subclinical kidney injury persists 1 year after significant weight loss induced by bariatric surgery, suggesting that close, long-term follow-up of kidney status is warranted in these adolescents.
Collapse
Affiliation(s)
- Nianzhou Xiao
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Prasad Devarajan
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Thomas H Inge
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Todd M Jenkins
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Michael Bennett
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Mark M Mitsnefes
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| |
Collapse
|
|
43
|
Piña Borrego CE, Fernández Fernández MDL, Fonte Rodríguez N, Piña Rodríguez LK. [Prediction instrument for obesity in adolescents at the Policlínico Universitario "Manuel González Díaz", 2013-2014]. BOLETIN MEDICO DEL HOSPITAL INFANTIL DE MEXICO 2015; 72:34-44. [PMID: 29421178 DOI: 10.1016/j.bmhimx.2015.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 02/02/2015] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Obesity is one of the principal non declarable diseases affecting children and adolescents. METHODS With the objective of developing a predictive instrument to identify high-risk adolescents with obesity, a cohort prospective study was carried out at the Policlinic "Manuel González Díaz", Bahía Honda City from 2013-2014. It was developed in three stages. In the first stage, 1800 adolescents from 10-19 years of age were included. The prevalence was identified and the most relevant characteristics of obesity were described (defined as body mass index >97th percentile according to age and sex). In the second stage we identified the possibility of the diagnosis of factors that increase the probability of obesity. The third stage elaborated and validated an obesity predictor instrument from the results of the initial stages. RESULTS To apply the instrument to sample A for internal elaboration and validation, sensitivity was 77.78% and specificity was 86.11%. Area under the curve (AUC) receiver operating characteristic (ROC) was 0.86, whereas for sample B the sensitivity was 79.63% and specificity was 92.13%. Positive predictive value (PPV) was 83.5% and negative predictive value (NPV) was 90.05%. CONCLUSIONS The instrument allows predicting the risk for developing obesity in adolescents with acceptable sensitivity and high specificity. Its routine application will be interesting in pediatric health consultations.
Collapse
Affiliation(s)
- Carlos Enrique Piña Borrego
- Servicio de Pediatría, Policlínico Universitario "Manuel González Díaz", Municipio Bahía Honda, Provincia de Artemisa, República de Cuba.
| | | | - Norge Fonte Rodríguez
- Medicina General Integral, Policlínico Universitario "Manuel González Díaz", Municipio Bahía Honda, Provincia de Artemisa, República de Cuba
| | | |
Collapse
|
|
44
|
Duzova A, Yalçinkaya F, Baskin E, Bakkaloglu A, Soylemezoglu O. Prevalence of hypertension and decreased glomerular filtration rate in obese children: results of a population-based field study. Nephrol Dial Transplant 2014; 28 Suppl 4:iv166-71. [PMID: 24179010 DOI: 10.1093/ndt/gft317] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Obesity has risen considerably in the Western world and the trend is increasing in non-Western, developing countries, as well. Several school screening studies showed the relation between body mass index and hypertension. In adults, obesity is associated with an increased risk of development and progression of kidney disease. However, data at the epidemiological level are limited, both for children and adults. The aim of this study was to determine the prevalence of obesity and evaluate its association with hypertension and glomerular filtration rate (GFR) among children in Turkey. METHODS A population-based field study in which individuals were accessed by house visits throughout Turkey has been conducted. The study sample (3622 children; 5-18 years; 49.6% female, mean age 11.88 ± 3.40 years) was selected to represent the Turkish population regarding geographical region, gender and age (5-18 years). Obesity was defined as the body mass index ≥95th percentile for age and gender. The Schwartz formula was used to estimate GFR. Blood pressure (BP) percentile was determined according to age, gender and length. RESULTS The prevalence of overweight, obesity and hypertension were 9.3, 8.9 and 6.1%, respectively. Logistic regression analysis revealed urban area (OR 1.50; 95% CI 1.15-1.96; P = 0.003) as an independent risk for obesity and age decreased (OR 0.921; 95% CI 0.890-0.924; P < 0.001) risk for obesity. Obese children had the highest rate of hypertension (11.4 versus 5.6%; P < 0.001; OR 2.17, 95% CI 1.49-3.17; P < 0.001) and stage II hypertension (3.8 versus 0.7%; OR 6.01, 95% CI 2.93-12.33; P < 0.001). Systolic and diastolic BP z-scores were significantly higher in obese children. The mean estimated (eGFR) was lower in obese children (122.7 ± 21.6 versus 129.4 ± 23.1, P < 0.001). The rates of children with eGFR < 90 and <75 mL/min/1.73 m(2) were higher in obese patients, but did not reach statistical significance. CONCLUSIONS Our nation-wide population-based field study among children showed that the prevalence of obesity is increasing in Turkey. The prevalence of hypertension and stage II hypertension, BP z-scores and eGFR were associated with obesity. We suggest that obese children are future candidates for chronic kidney disease. Longitudinal research is necessary to better understand these associations. Strategies for the prevention and management of obesity are also important for emerging countries and for children.
Collapse
Affiliation(s)
- Ali Duzova
- Division of Paediatric Nephrology and Rheumatology, Department of Paediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | | | | | | | | |
Collapse
|
|
45
|
Gunta SS, Mak RH. Hypertension in children with obesity. World J Hypertens 2014; 4:15-24. [DOI: 10.5494/wjh.v4.i2.15] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Revised: 05/04/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
The prevalence of obesity related hypertension has dramatically increased in children with the parallel increase in pediatric obesity. This pediatric health problem may adversely affect cardiovascular health in adult life. The pathogenesis of hypertension in obese children is not widely understood. We therefore undertake this review to raise public awareness. Early childhood parameters like birth weight and postnatal weight gain may play important roles in risk for obesity and obesity related hypertension later in childhood and adult life. Further information is required to confirm this origin of hypertension so that appropriate measures are taken in the peri-natal period. The role of sympathetic nervous system has now been well established as one of the principle mechanisms involved in obesity related hypertension. The Renin-Angiotensin system, insulin resistance due to obesity and as a part of metabolic syndrome along with imbalance in adipokines such as leptin and adiponectin, cause activation of the sympathetic system, vasoconstriction, endothelial dysfunction and sodium reabsorption among other perturbations. Multi-step interventions targeting these various mechanisms are required to break the cycle of obesity and metabolic syndrome. Vitamin D deficiency, sleep apnea due to airway obstruction and hyperuricemia may also play a significant role and should not be ignored in its early stages. Obesity is a risk factor for other co-morbid conditions like chronic kidney disease and fatty liver which further accentuate the risk of hypertension. Increased awareness is required to prevent, diagnose and treat obesity related hypertension among the pediatric population.
Collapse
|
|
46
|
Abstract
The occurrence and progression of nephropathy associated with early onset type 2 diabetes (T2D) is a consequence of the ongoing epidemic of childhood obesity. Minimal evidence regarding treatment effectiveness of renovascular comorbidities in youth with early onset T2D is available, due to the relatively recent emergence of T2D in youth and young adults. Extrapolation of adult therapy guidelines is not an ideal approach to making therapeutic decisions in this population. Evolving management and intervention strategies are based on accumulating longitudinal data from cohorts of well characterized youth and young adults with T2D. The degree of similarity in histologic findings and disease specific characteristics of kidney disease in patients with early onset T2D and albuminuria compared with affected adults is not well characterized. Early aggressive therapies to minimize the impact of nephropathy are indicated as the evidence for best therapies in youth with T2D are further explored.
Collapse
Affiliation(s)
- Carolina Solis-Herrera
- Resident, Internal Medicine, Texas Tech University Health Science Center at Permian Basin, 5075 East 52 St. #J305, Odessa, TX 79762, Phone: 210-619-3264
| | - Curtis L. Triplitt
- Texas Diabetes Institute, Clinical Assistant Professor, Department of Medicine, Div. of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, Phone:210-358-7228, Fax:210-358-7235
| | - Jane L. Lynch
- Professor of Pediatrics, University of Texas Health Science Center, 7703 Floyd Curl Dr. (MS 7806), San Antonio, TX 78229, Phone: 210-567-5213, Fax: 210-567-0492
| |
Collapse
|
|
47
|
Gunta SS, Mak RH. Is obesity a risk factor for chronic kidney disease in children? Pediatr Nephrol 2013; 28:1949-56. [PMID: 23150030 DOI: 10.1007/s00467-012-2353-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2012] [Revised: 10/04/2012] [Accepted: 10/05/2012] [Indexed: 12/13/2022]
Abstract
There is a rapid increase worldwide in the prevalence of obesity in adults and children. Obesity is not only a comorbidity for chronic kidney disease (CKD) but may also be a risk factor for CKD. Epidemiological correlations and pathophysiological changes have been observed associating obesity with CKD. Low birth weight may be associated with both obesity and low nephron mass, leading to CKD later in life. Elevated levels of adipokines, such as leptin and adiponectin, in obesity may be factors in CKD pathogenesis and progression. Furthermore, various other factors, such as hypertension, increased cardiovascular morbidity, insulin resistance, dyslipidemia, and lipotoxicity, may play significant roles in the pathogenesis of CKD in obesity. Reduction in obesity, which is a potentially modifiable risk factor, might help decrease the burden of CKD in the population. Apart from individualized options, community-based interventions have the potential to create a strong impact in this condition.
Collapse
Affiliation(s)
- Sujana S Gunta
- Division of Pediatric Nephrology, Rady Children's Hospital San Diego, University of California, San Diego, 9500 Gilman Drive. MC 0634, La Jolla, CA 92093-0634, USA
| | | |
Collapse
|
|
48
|
Abstract
OBJECTIVE Among adolescents with type 2 diabetes, there is limited information regarding incidence and progression of hypertension and microalbuminuria. Hypertension and microalbuminuria assessments made during the TODAY clinical trial were analyzed for effect of treatment, glycemic control, sex, and race/ethnicity. RESEARCH DESIGN AND METHODS A cohort of 699 adolescents, 10-17 years of age, <2 years duration of type 2 diabetes, BMI ≥ 85%, HbA1c ≤ 8% on metformin therapy, controlled blood pressure (BP), and calculated creatinine clearance >70 mL/min, were randomized to metformin, metformin plus rosiglitazone, or metformin plus intensive lifestyle intervention. Primary study outcome was loss of glycemic control for 6 months or sustained metabolic decompensation requiring insulin. Hypertension and microalbuminuria were managed aggressively with standardized therapy to maintain BP <130/80 or <95th percentile for age, sex, and height and microalbuminuria <30 μg/mg. RESULTS In this cohort, 319 (45.6%) reached primary study outcome, and 11.6% were hypertensive at baseline and 33.8% by end of study (average follow-up 3.9 years). Male sex and higher BMI significantly increased the risk for hypertension. Microalbuminuria was found in 6.3% at baseline and rose to 16.6% by end of study. Diagnosis of microalbuminuria was not significantly different between treatment arms, sex, or race/ethnicity, but higher levels of HbA1c were significantly related to risk of developing microalbuminuria. CONCLUSIONS Prevalence of hypertension and microalbuminuria increased over time among adolescents with type 2 diabetes regardless of diabetes treatment. The greatest risk for hypertension was male sex and higher BMI. The risk for microalbuminuria was more closely related to glycemic control.
Collapse
|
|
49
|
Shi X, Tubb L, Fingers ST, Chen S, Caffrey JL. Associations of physical activity and dietary behaviors with children's health and academic problems. THE JOURNAL OF SCHOOL HEALTH 2013; 83:1-7. [PMID: 23253284 DOI: 10.1111/j.1746-1561.2012.00740.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
BACKGROUND We examined the associations of physical activities and dietary behaviors with children's health and academic-behavioral problems. METHODS We employed a Community-wide Children's Health Assessment and Planning Survey to examine physical activity, healthy meals, health status, and academic-behavioral problems in 3708 children 7 to 14 years of age. Statistical associations were examined with chi-square test and logistic regression analysis; we calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Among these children, 30.2% were overweight-obese, 11.0% had academic problems, and 7.9% had behavioral problems. Children classified as healthy eaters were more likely to exercise ≥4 days/week (79.1% vs 64.6%, OR: 2.08, 95% CI: 1.14 to 2.49), less likely to be overweight-obese (27.7% vs 44.6%, OR: 0.48, CI: 0.31 to 0.73), less likely to have academic problems (9.1% vs 16.1%, OR: 0.57, 95% CI: 0.41 to 0.79) and behavioral problems (6.9% vs 13.9%, OR: 0.46, 95% CI: 0.32 to 0.66) compared with their less healthy eating peers. Physical activity and healthy meals were associated with an improved health status (p < .001). However, the proportions of children taking unhealthy meals or choosing sedentary lifestyle increased as the cohorts progressed (p < .05) from childhood (7 to 8 years) to adolescence (13 to 14 years). CONCLUSIONS Healthy (or unhealthy) lifestyle behaviors are significantly interrelated. Children who take healthy meals and exercise often are associated with better health and fewer academic and behavioral problems. Unfortunately, taking unhealthy meals and sedentary lifestyle characterize a growing proportion of young adolescents. Thus, curbing unhealthy lifestyle behaviors should start in early childhood.
Collapse
Affiliation(s)
- Xiangrong Shi
- Department of Integrative Physiology, Cardiovascular Research Institute and Texas Prevention Institute, UNT Health Science Center, Fort Worth, TX 76107, USA.
| | | | | | | | | |
Collapse
|
|
50
|
Li Y, Sun X, Yu Y. Serum fetuin-A levels related with microalbuminuria in diet-induced obese rats. BIOMED RESEARCH INTERNATIONAL 2012; 2013:795103. [PMID: 23710462 PMCID: PMC3591142 DOI: 10.1155/2013/795103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2012] [Revised: 11/29/2012] [Accepted: 12/04/2012] [Indexed: 02/07/2023]
Abstract
The aim of the study was to investigate the association between elevated serum fetuin-A and increased urine albumin excretion in obese rats, and whether increased urine albumin excretion was modified by improving hepatic steatosis and lipid metabolism disorder. Male Wistar rats 4 weeks in age were randomly divided into three groups and fed with normal chow (control group), high-fat chow (obesity group), or high-fat chow plus fenofibrate (fenofibrate group). After 24 weeks, both body weight and visceral fat/body weight ratio in obese rats were higher than in controls. A difference in serology markers and pathology associated with hepatic steatosis was also found among the three groups. Serum fetuin-A and the expression of NF- κ B in the liver were increased, while serum adiponectin was decreased in obese rats in comparison to controls (P < 0.01). Urinary albumin/creatinine ratio (ACR) was increased in the obesity group compared to controls (P < 0.01). The fenofibrate intervention reduced serum fetuin-A and NF- κ B expression in the liver and increased serum adiponectin compared to obese rats and was accompanied by decrease in ACR. A positive correlation was found between ACR and fetuin-A (r = 0.602, P < 0.01), and a negative correlation was found between ACR and adiponectin (r = -0.635, P < 0.01). We conclude that elevated fetuin-A levels are associated with microalbuminuria in obese rats, and abnormal albuminuria is reversible by improving hepatic steatosis.
Collapse
Affiliation(s)
- Yanyan Li
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xiaodong Sun
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yerong Yu
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| |
Collapse
|