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Godinho N, Morato M, Albino-Teixeira A, Caldas Afonso A, Sousa T, Correia-Costa L. Gender-related differences in cardiometabolic risk factors and oxidative stress among prepubertal children with obesity. J Pediatr Endocrinol Metab 2024; 37:42-51. [PMID: 38054937 DOI: 10.1515/jpem-2023-0286] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 11/09/2023] [Indexed: 12/07/2023]
Abstract
OBJECTIVES Gender-related differences in oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors were examined in a cross-sectional study involving 313 prepubertal children (8-9 years old) from the generation XXI birth-cohort. METHODS Anthropometric measurements, cardiometabolic variables, and redox markers were assessed, including plasma and urinary isoprostanes (P-Isop, U-Isop), plasma total antioxidant status (P-TAS), serum myeloperoxidase (MPO), plasma and urinary nitrates and nitrites (P-NOX, U-NOX), and urinary hydrogen peroxide (U-H2O2). RESULTS Girls showed higher levels of total/non-HDL cholesterol, triglycerides, and insulin resistance (HOMA-IR) compared to boys. Notably, U-H2O2 values were lower in girls. When stratifying by body mass index (BMI) and gender, both girls and boys exhibited higher MPO concentration and U-Isop values. Uric acid concentration was higher in overweight and obese girls than in normal weight girls, while no significant differences were observed among boys across BMI categories. Furthermore, U-NOX values differed only in boys, with higher levels observed in overweight and obese individuals compared to those with normal weight. Multivariate analysis, adjusted for age and BMI z-score, demonstrated inverse associations between U-H2O2 and pulse wave velocity values, as well as between U-NOX and total or non-HDL cholesterol, exclusively in boys. In girls, a positive association between U-Isop and HOMA-IR values was observed. CONCLUSIONS In conclusion, gender differentially impacts oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors in prepubertal children. Prepubertal girls appear more susceptible to oxidative stress-induced metabolic dysfunction, while in boys, elevated levels of redox and nitric oxide bioavailability markers seem to provide protection against arterial stiffness and lipid homeostasis.
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Affiliation(s)
- Nelson Godinho
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Manuela Morato
- Laboratório de Farmacologia, Departamento de Ciências do Medicamento, Faculdade de Farmácia, Universidade do Porto (FFUP), Porto, Portugal
- LAQV/REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
| | - António Albino-Teixeira
- MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa da Universidade do Porto, Porto, Portugal
- Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
| | - Alberto Caldas Afonso
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
- EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
- Unidade de Nefrologia Pediátrica, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Teresa Sousa
- MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa da Universidade do Porto, Porto, Portugal
- Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
| | - Liane Correia-Costa
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
- EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal
- Unidade de Nefrologia Pediátrica, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário de Santo António, Porto, Portugal
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An X, Li G, Wang S, Xie T, Ren X, Zhao Y. Renoprotection by Inhibiting Connexin 43 Expression in a Mouse Model of Obesity-Related Renal Injury. Diabetes Metab Syndr Obes 2023; 16:1415-1424. [PMID: 37220614 PMCID: PMC10200121 DOI: 10.2147/dmso.s412546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 05/02/2023] [Indexed: 05/25/2023] Open
Abstract
Introduction Our previous study conducted in an obesity-related renal injury rat model have established a connection between increased connexin 43 (Cx43) expression and renal injury. In this study, we investigated whether inhibiting Cx43 expression could provide renoprotection in a mouse model of obesity-related renal injury. Methods Five-week-old C57BL/6J mice were fed with a high-fat diet for 12 weeks to establish an obesity-related renal injury model, then they were treated with Cx43 antisense oligodeoxynucleotide (AS) or scrambled oligodeoxynucleotide (SCR) by an implanted osmotic pump for 4 weeks. Finally, the glomerular filtration function, the histological change in the glomeruli, and the markers of podocyte injury (WT-1, Nephrin) and inflammatory infiltration of renal tissue (CD68, F4/80 and VCAM-1) were examined respectively. Results The results showed that inhibiting Cx43 expression by AS in this mouse model of obesity-related renal injury can effectively improve glomerular filtration function, alleviate glomerular expansion and podocyte injury, and attenuate the inflammatory infiltration of renal tissue. Conclusion Our results demonstrated that inhibiting Cx43 expression by AS could provide renoprotection for the mouse model of obesity-related renal injury.
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Affiliation(s)
- Xiaomin An
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China
- Department of Nephrology, Xi’an Children’s Hospital, Xi’an, 710003, People’s Republic of China
| | - Guohua Li
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China
| | - Shu Wang
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China
| | - Tianrun Xie
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China
| | - Xiaoxiao Ren
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China
| | - Yongli Zhao
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of China
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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?
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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
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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.
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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.
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Assessment of renal function in obese and overweight children with NGAL and KIM-1 biomarkers. NUTR HOSP 2021; 34:436-442. [PMID: 32207310 DOI: 10.20960/nh.02651] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Introduction Aim and background: the incidence of obesity has increased among children, and obesity has been considered an independent risk factor for chronic kidney disease. We aimed to determine the degree of kidney function impairment by evaluating urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels. Materials and methods: in total, 15 obese, 26 overweight, and 26 control adolescents aged 10 to 16 years were enrolled into the study. Urine samples were evaluated for NGAL and KIM-1 levels using enzyme-linked immunosorbent assay kits. We investigated the association between obesity and related comorbidities with urinary NGAL and KIM-1 excretion. Results: no significant differences were noted between the obese, overweight, and control groups in urinary NGAL and KIM-1 excretion (p = 0.327 and p = 0.917, respectively). In the obese and overweight groups urinary NGAL levels were 50.39 [30.88-74.22] in females and 26.67 [23.24-45.59] in males (p = 0.013). Also, urinary NGAL levels were increased in obese and overweight adolescents with LDL dyslipidemia at 64.12 [30.98-114.32] as compared to those without LDL dyslipidemia: 39.51 [25.59.56.37] (p = 0.024). Furthermore, a correlation was observed between insulin and homeostasis model assessment of insulin resistance levels with the NGAL/creatinine ratio in the overweight group (r = 0.515; p = 0.008, and r = 0.483; p = 0.014, respectively). Such correlation was not found in the obese group. Conclusion: the effect of obesity on renal function could not be determined in children. A longer exposure may be required for obesity-induced disruption of renal function in children. Renal function may be disrupted by dyslipidemia in obese adolescents. Furthermore, obesity impaired renal function in female adolescents. The normalization of these urinary markers as related to urine creatinine should be discussed.
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Polidori N, Giannini C, Salvatore R, Pelliccia P, Parisi A, Chiarelli F, Mohn A. Role of urinary NGAL and KIM-1 as biomarkers of early kidney injury in obese prepubertal children. J Pediatr Endocrinol Metab 2020; 33:1183-1189. [PMID: 32845866 DOI: 10.1515/jpem-2020-0138] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/28/2020] [Indexed: 01/04/2023]
Abstract
Objectives Childhood obesity is an important cause of end-stage renal disease. To date, available markers do not characterize kidney changes, especially in the early stages. kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are already detected before the onset of proteinuria or alterations of glomerular filtration rate and thus might represent biomarkers that directly reflect kidney injury. Methods We characterize kidney injury in a group of 40 obese-prepubertal children compared to 29-healthy age- and gender matched-peers. Anthropometric measurements and body composition were determined. Fasting blood samples were collected for measurement of insulin, glucose, lipid profile, transaminases, cystatin C and creatinine. Urine samples were collected to assess urinary NGAL, KIM-1 and urinary isoprostanes. Kidney length was measured with ultrasound evaluation. Differences between the two groups were evaluated by Mann-Whitney U test, and Spearman correlation analysis was used to explore relationship between variables. Results Triglycerides, alanine transaminase (ALT), glucose, insulin, homeostasis model assessment insulin resistance, triglycerides/high-density lipoprotein (HDL)-cholesterol ratio and cystatin C values were significantly higher in obese children than normal weight peers. Creatinine values were normal and similar between the two groups, while isoprostanes were higher in obese. Obese children had larger kidney sizes, indicating organ hypertrophy. NGAL and KIM-1 were increased in obese children compared to controls. A significant association between NGAL and KIM-1 with adiposity indices, insulin status and markers of oxidative stress postulated a possible effect of obesity in inducing kidney abnormalities. KIM-1 and NGAL are directly related respectively to cystatin C and isoprostanes, supporting the ability of these biomarkers in reflecting early kidney damages in obese subjects. Conclusions These findings suggest that obese subjects exhibit a certain degree of renal damage before kidney function loss.
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Affiliation(s)
- Nella Polidori
- Department of Pediatrics, University of Chieti, Chieti, Italy
| | - Cosimo Giannini
- Department of Pediatrics, University of Chieti, Chieti, Italy
| | | | | | - Adriana Parisi
- Department of Pediatrics, University of Chieti, Chieti, Italy
| | | | - Angelika Mohn
- Department of Pediatrics, University of Chieti, Chieti, Italy
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Yodoshi T, Arce-Clachar AC, Sun Q, Fei L, Bramlage K, Xanthakos SA, Flores F, Mouzaki M. Glomerular Hyperfiltration Is Associated with Liver Disease Severity in Children with Nonalcoholic Fatty Liver Disease. J Pediatr 2020; 222:127-133. [PMID: 32381466 PMCID: PMC8218655 DOI: 10.1016/j.jpeds.2020.03.038] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 02/20/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To determine the prevalence of renal impairment in a large cohort of youths with histologically confirmed nonalcoholic fatty liver disease (NAFLD), and to determine its association with liver disease severity. STUDY DESIGN Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD at a tertiary care center between 2010 and 2017. Histological NAFLD severity was scored using validated criteria. Glomerular filtration rate (GFR) was calculated and categorized as low (<90 mL/min/1.73 m2), normal (90-136 mL/min/1.73 m2), or high (>136 mL/min/1.73 m2). Univariate and multivariate modeling were used to determine differences between the GFR groups and to control for confounders. RESULTS The cohort comprised 179 patients (82% non-Hispanic; median age; 14 years; IQR, 12-16 years). One-third of the patients had abnormal renal function, including 36 (20%) with glomerular hyperfiltration and 26 (15%) with low GFR. In multivariable logistic regression, compared with normal GFR, hyperfiltration was independently associated with higher NAFLD activity score (aOR, 2.96; 95% CI, 1.49-5.87; P = .002), after adjusting for age, sex, ethnicity, obesity severity, presence of type 2 diabetes mellitus, and medications. CONCLUSIONS In this large cohort with histologically confirmed NAFLD, renal impairment was highly prevalent and associated with liver disease severity, independent of obesity severity. Screening patients with confirmed NAFLD for renal complication is recommended.
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Affiliation(s)
- Toshifumi Yodoshi
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Ana Catalina Arce-Clachar
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH
| | - Qin Sun
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Lin Fei
- Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Kristin Bramlage
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Stavra A Xanthakos
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH
| | - Francisco Flores
- Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH; Division of Nephrology and Hypertension, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Marialena Mouzaki
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH.
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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.
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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.
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Di Bonito P, Valerio G, Licenziati MR, Miraglia Del Giudice E, Baroni MG, Morandi A, Maffeis C, Campana G, Spreghini MR, Di Sessa A, Morino G, Crinò A, Chiesa C, Pacifico L, Manco M. High uric acid, reduced glomerular filtration rate and non-alcoholic fatty liver in young people with obesity. J Endocrinol Invest 2020; 43:461-468. [PMID: 31637675 DOI: 10.1007/s40618-019-01130-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 10/12/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the association between high uric acid (UA), reduced estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) in outpatient children and adolescents with overweight (OW) or obesity (OB). METHODS Anthropometric, biochemical, hepatic ultrasound and eGFR data were available from 2565 young people with OW/OB (age 5-18 years). eGFR was calculated using the Schwartz's bedside formula and reduced eGFR (ReGFR+) was defined by a value < 90 mL/min/1.73 m2. High UA was defined as ≥ 75th percentile by sex in children and adolescents. RESULTS The population was stratified in four categories: (1) normal eGFR and absence of NAFLD (ReGFR-/NAFLD-) (n = 1,236); (2) ReGFR+ and absence of NAFLD (ReGFR+/NAFLD- (n = 155); (3) normal eGFR and presence of NAFLD (ReGFR-/NAFLD+) (n = 1019); (4) presence of both conditions (ReGFR+/NAFLD+) (n = 155). Proportions of youth with high UA across the four categories were 17%, 30%, 33% and 46%, respectively (P < 0.0001). Young people with high levels of UA had odds ratio (95% CI) of 2.11 (1.43-3.11) for ReGFR+; 2.82 (2.26-3.45) for NAFLD+; and 5.04 (3.45-7.39) for both conditions (P < 0.0001 for all), independently of major confounders. CONCLUSIONS High levels of UA were independently associated with ReGFR, NAFLD and the combination of both conditions in young people with OW/OB. The strength of this association was the highest in cases presenting both reduced eGFR and NAFLD. UA may serve as marker to identify patients at risk for these conditions.
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Affiliation(s)
- P Di Bonito
- Department of Internal Medicine, "S. Maria delle Grazie" Hospital, Pozzuoli, Italy
| | - G Valerio
- Department of Movement Sciences and Wellbeing, University "Parthenope", Naples, Italy
| | - M R Licenziati
- Obesity and Endocrine Disease Unit, Department of Neuroscience, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - E Miraglia Del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - M G Baroni
- Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
| | - A Morandi
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - C Maffeis
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - G Campana
- Obesity and Endocrine Disease Unit, Department of Neuroscience, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - M R Spreghini
- Research Area for Multifactorial Disease, Children's Hospital Bambino Gesù, Via Ferdinando Baldelli 38, 00146, Rome, Italy
| | - A Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - G Morino
- Research Area for Multifactorial Disease, Children's Hospital Bambino Gesù, Via Ferdinando Baldelli 38, 00146, Rome, Italy
| | - A Crinò
- Research Area for Multifactorial Disease, Children's Hospital Bambino Gesù, Via Ferdinando Baldelli 38, 00146, Rome, Italy
| | - C Chiesa
- Institute of Translational Pharmacology, National Research Council, Rome, Italy
| | - L Pacifico
- Policlinico Umberto I Hospital, "Sapienza" University of Rome, Rome, Italy
| | - M Manco
- Research Area for Multifactorial Disease, Children's Hospital Bambino Gesù, Via Ferdinando Baldelli 38, 00146, Rome, Italy.
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10
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Battaglia Y, Esposito P, Corrao S, Russo L, Balducci A, Storari A, Russo D. Evaluation of Hypertension, Proteinuria, and Abnormalities of Body Weight in Italian Adolescents Participating in the World Kidney Days. Kidney Blood Press Res 2020; 45:286-296. [PMID: 32036372 DOI: 10.1159/000502547] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/06/2019] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION World Kidney Day (WKD) was promoted by the Italian Kidney Foundation and the Italian Society of Nephrology for raising awareness, detection, prevention, and treatment of kidney diseases. The Italian WKD focused on the "School Project" by screening students attending the fifth year of high school. The main goal of the "School Project" was to assess in healthy adolescents the presence of hypertension (HTN) and proteinuria; as well as to evaluate potential interrelations between overweight, obesity (both measured with different anthropometric methods), blood pressure (BP) levels, and proteinuria. The ancillary goal was to have an estimate of awareness on some nephrology topics. METHODS The study population consisted of 17- to 19-year-old students. HTN was defined as systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg. Isolated systolic hypertension (ISH) was defined as SBP ≥140 mm Hg and DBP <90 mm Hg; isolated diastolic hypertension as SBP <140 mm Hg and DBP ≥90 mm Hg; systolic and diastolic hypertension as SBP ≥140 mm Hg and DBP ≥90 mm Hg; pre-hypertension as SBP >120 mm Hg but <140 mm Hg or DBP >80 mm Hg but <90 mm Hg; and optimal BP as SBP ≤120 mm Hg and DBP ≤80 mm Hg. Urine tests were performed with a dipstick; the subjects were regarded as proteinuric when the urine dipstick was positive (proteinuria ≥30 mg/dL). Body weight, height, and waist circumference (WC) were measured; body mass index (BMI), waist-to-height ratio (WHtR), and conicity index (Ci) were calculated. According to the BMI, the following classifications were adopted: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), class-I obesity (30-34.9 kg/m2), class-II obesity (35-39.9 kg/m2), class-III obesity (≥40 kg/m2). RESULTS Data from 12,125 students (45.6% males) were evaluated. HTN was found in 1,349 participants (11.1%; 61.1% male), and ISH was present in 7.4%. Overweight (24.1%) and class-I (6%), -II (3.6%), and -III (1%) obesity were present in hypertensive participants. Compared to participants with normal BP, hypertensive participants had a higher BMI (p < 0.001), WC (p < 0.001), and WHtR (p < 0.001); whereas the Ci was not different (p = 0.527). Multivariate linear regression analysis showed that both WC and BMI were predictors of abnormal SBP and DBP (p < 0.001) both in males and females. Proteinuria was present in 14.8, 13.8, 14.7, and 14.7% of all normal weight, overweight, obese, and all subjects, respectively. In addition, no association was found between body weight, proteinuria, and BP. CONCLUSION This study shows that overweight and obesity were significantly associated to HTN in Italian adolescents. BMI and WC were predictors of SBP and DBP. The occurrence of proteinuria was quite similar to that of HTN, but it was not associated with anthropometric indicators or HTN.
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Affiliation(s)
- Yuri Battaglia
- Division of Nephrology and Dialysis, University-Hospital St. Anna, Ferrara, Italy,
| | - Pasquale Esposito
- Nephrology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Salvatore Corrao
- Internal Medicine Unit, National Relevance and High Specialization Hospital Trust, Palermo, Italy
| | - Luigi Russo
- Nephrology Unit, Ospedale del Mare, Naples, Italy
| | | | - Alda Storari
- Division of Nephrology and Dialysis, University-Hospital St. Anna, Ferrara, Italy
| | - Domenico Russo
- Department of Public Health, Nephrology Unit, University Federico II, Naples, Italy
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11
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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.
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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
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12
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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.
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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.
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13
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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.
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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
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14
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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.
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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
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15
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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.
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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
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16
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Xiong Y, Fukuda T, Knibbe CAJ, Vinks AA. Drug Dosing in Obese Children: Challenges and Evidence-Based Strategies. Pediatr Clin North Am 2017; 64:1417-1438. [PMID: 29173794 DOI: 10.1016/j.pcl.2017.08.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
With the alarming increase of obesity in children, pediatricians are increasingly being confronted with difficult dosing decisions. Many drug labels do not provide specific dosing instructions for children who are obese. In this article, we describe the physiologic parameters altered by obesity and their influences on drug disposition and effect. We review the principles of allometry, and the key pharmacokinetic parameters that can be used to derive age appropriate dosing regimens. Last, we illustrate how appropriate weight descriptors can be selected, and how important PK parameters can be extrapolated for dosing in obese children when pediatric pharmacokinetic information is available.
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Affiliation(s)
- Ye Xiong
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 6018, Cincinnati, OH 45229-3039, USA
| | - Tsuyoshi Fukuda
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 6018, Cincinnati, OH 45229-3039, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Catherijne A J Knibbe
- Department of Clinical Pharmacy, St Antonius Hospital, PO Box 2500, Nieuwegein 3430 EM, The Netherlands; Division of Pharmacology, Leiden Academic Center for Drug Research, Faculty of Science, Leiden University, PO Box 9502, 2300 RA, Leiden, The Netherlands
| | - Alexander A Vinks
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 6018, Cincinnati, OH 45229-3039, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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Cho H, Kim JH. Prevalence of microalbuminuria and its associated cardiometabolic risk factors in Korean youth: Data from the Korea National Health and Nutrition Examination Survey. PLoS One 2017; 12:e0178716. [PMID: 28575100 PMCID: PMC5456094 DOI: 10.1371/journal.pone.0178716] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 05/17/2017] [Indexed: 12/18/2022] Open
Abstract
Background Microalbuminuria is a known early predictive factor for renal and cardiovascular diseases, not only for patients with diabetes mellitus or hypertension but also in the general population. However, the prevalence and risk factors associated with microalbuminuria in Korean youth are unknown. Objectives The aims of this study are to evaluate the prevalence of microalbuminuria and the association between microalbuminuria and obesity or cardiometabolic risk factors in Korean children and adolescents without diabetes. Methods This study examines data obtained from the Korea National Health and Nutrition Examination Survey (between 2011 and 2014). It includes a total of 1,976 participants aged between 10 and 19 years (boys 1,128 and girls 848). Microalbuminuria was defined as a urine albumin-to-creatinine ratio (UACR) of ≥ 30 mg/g and < 300 mg/g. Association between microalbuminuria and the risk factors for cardiometabolic diseases including insulin resistance was evaluated. Results The prevalence of microalbuminuria was found to be 3.0% in Korean children and adolescents over this time period. The mean UACR for non-obese youth was significantly greater than that found in obese youth (3.2 ± 0.1 mg/g in the non-obese group vs. 2.1 ± 0.2 mg/g in the obese group; P < 0.001). In multiple logistic regression analysis, microalbuminuria was associated with hyperglycemia (OR 2.62, 95% CI 1.09–6.30) and hemoglobin A1c (OR 3.34, 95% CI 1.09–10.17) in the non-obese group and hypertension (OR 14.10, 95% CI 1.12–177.98) and HbA1c (OR 6.68, 95% CI 1.87–23.95) in the obese group. Conclusions The prevalence of microalbuminuria is not prominent in obese children and adolescents. Our findings demonstrated that the presence of hypertension and hyperglycemia was associated with microalbuminuria. Especially Hemoglobin A1c was associated with microalbuminuria in youths regardless of weight status. Microalbuminuria in pediatric population can be a helpful marker for the risk of cardiovascular disease.
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Affiliation(s)
- Heeyeon Cho
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Hyun Kim
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- * E-mail:
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Övünç Hacıhamdioğlu D, Hacıhamdioğlu B, Altun D, Müftüoğlu T, Karademir F, Süleymanoğlu S. Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children. J Clin Res Pediatr Endocrinol 2016; 8:282-7. [PMID: 27087488 PMCID: PMC5096491 DOI: 10.4274/jcrpe.2828] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
OBJECTIVE Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children. METHODS A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated. RESULTS Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001). CONCLUSION In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children.
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Affiliation(s)
- Duygu Övünç Hacıhamdioğlu
- Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, Clinic of Child Health and Diseases, İstanbul, Turkey E-mail:
| | - Bülent Hacıhamdioğlu
- Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, Clinic of Child Health and Diseases, İstanbul, Turkey
| | - Demet Altun
- Etimesgut Military Hospital, Clinic of Pediatrics, Ankara, Turkey
| | - Tuba Müftüoğlu
- Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, Clinic of Biochemistry, İstanbul, Turkey
| | - Ferhan Karademir
- Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, Clinic of Child Health and Diseases, İstanbul, Turkey
| | - Selami Süleymanoğlu
- Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, Clinic of Child Health and Diseases, İstanbul, Turkey
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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.
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20
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Yim HE, Yoo KH, Bae IS, Hong YS. Early Treatment With Enalapril and Later Renal Injury in Programmed Obese Adult Rats. J Cell Physiol 2016; 232:447-455. [DOI: 10.1002/jcp.25444] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 05/26/2016] [Indexed: 12/21/2022]
Affiliation(s)
- Hyung Eun Yim
- Department of Pediatrics; College of Medicine; Korea University; Seoul Korea
| | - Kee Hwan Yoo
- Department of Pediatrics; College of Medicine; Korea University; Seoul Korea
| | - In Sun Bae
- Department of Pediatrics; College of Medicine; Korea University; Seoul Korea
| | - Young Sook Hong
- Department of Pediatrics; College of Medicine; Korea University; Seoul Korea
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21
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Arimura E, Pulong WP, Marchianti ACN, Nakakuma M, Abe M, Ushikai M, Horiuchi M. Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion. Eur J Nutr 2015; 56:237-246. [PMID: 26497335 DOI: 10.1007/s00394-015-1075-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 10/08/2015] [Indexed: 12/18/2022]
Abstract
PURPOSE We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice. METHODS In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured. RESULTS The db-H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db-L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db-L mixture mice showed significantly higher blood glucose after 30 min than db-H mixture mice. However, db mice administered starch-H mixture showed significantly higher blood glucose 120-300 min post-administration than db-L mixture mice, although both groups exhibited similar insulin levels. CONCLUSIONS High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.
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Affiliation(s)
- Emi Arimura
- Major in Food and Nutrition, Department of Life and Environmental Science, Kagoshima Prefectural College, 1-52-1 Shimo-Ishiki, Kagoshima, 890-0005, Japan
- Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Wijang Pralampita Pulong
- Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Ancah Caesarina Novi Marchianti
- Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
- Medical Faculty of Jember University, Kalimantan Street 37, East Java, Indonesia
| | - Miwa Nakakuma
- Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
- Takata Hospital, 5-1 Horie-cho, Kagoshima, 892-0824, Japan
| | - Masaharu Abe
- Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Miharu Ushikai
- Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Masahisa Horiuchi
- Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
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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.
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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
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Goknar N, Oktem F, Ozgen IT, Torun E, Kuçukkoc M, Demir AD, Cesur Y. Determination of early urinary renal injury markers in obese children. Pediatr Nephrol 2015; 30:139-44. [PMID: 24801174 DOI: 10.1007/s00467-014-2829-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Revised: 03/27/2014] [Accepted: 04/10/2014] [Indexed: 01/09/2023]
Abstract
BACKGROUND Obesity is an important health issue, the prevalence of which is increasing in childhood. The aim of this study was to examine urinary renal injury markers in order to determine the renal effect of obesity and its comorbidities in a pediatric population. METHODS Eighty-four obese children and 64 healthy control subjects were enrolled in the study. We checked their urine using N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and microalbumin as renal injury markers. Associations of renal damage markers with hypertension, an impaired glucose tolerance test, and insulin resistance were assessed. RESULTS Obese individuals had higher urinary NAG and KIM-1 values compared to those of healthy controls (p = 0.027, p = 0.026). There was no difference in urinary NGAL between obese and lean subjects (p = 0.885). Urinary renal injury markers were not statistically different in the obese group when checked for impaired glucose tolerance, insulin resistance, and hypertension (p > 0.05). CONCLUSIONS This study shows that urinary NAG and KIM-1 could be used as a screening method for detection of early renal damage in obese children.
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Affiliation(s)
- Nilufer Goknar
- Department of Pediatric Nephrology, Bezmialem Vakif University Medical Faculty, Istanbul, Turkey
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24
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Out-of-office blood pressure and target organ damage in children and adolescents. J Hypertens 2014; 32:2315-31; discussion 2331. [DOI: 10.1097/hjh.0000000000000384] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Bakker H, Kooijman MN, van der Heijden AJ, Hofman A, Franco OH, Taal HR, Jaddoe VWV. Kidney size and function in a multi-ethnic population-based cohort of school-age children. Pediatr Nephrol 2014; 29:1589-98. [PMID: 24599444 DOI: 10.1007/s00467-014-2793-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 01/21/2014] [Accepted: 02/13/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Subclinical impaired kidney growth and function in childhood may lead to kidney diseases and high blood pressure in adulthood. We assessed the cross-sectional associations of childhood characteristics with kidney size and function in a multi-ethnic cohort. METHODS This study was embedded in a population-based cohort study of 6,397 children with a median age of 6.0 years.Kidney volume, creatinine and cystatin C blood levels, microalbuminuria and blood pressure were measured, and glomerular filtration rate (GFR) was estimated. RESULTS Childhood anthropometrics were positively associated with kidney volume, creatinine level and blood pressure (all p < 0.05). We observed ethnic differences in all kidney size and function measures (all p < 0.05). Children with smaller kidneys had higher creatinine and cystatin C blood levels, leading to a lower estimated GFR [difference 5.68 ml/min/1.73 m2 (95% confidence interval 5.14-6.12) per 1 standard deviation increase in kidney volume]. Larger kidney volume was associated with an increased risk of microalbuminuria. CONCLUSIONS Childhood kidney volume and function are influenced by body mass index and ethnicity. Kidney volume is related with kidney function but not with blood pressure. These results may help to identify individuals at risk for kidney disease in an early stage.
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Affiliation(s)
- Hanneke Bakker
- The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands
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26
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Di Bonito P, Sanguigno E, Forziato C, Di Fraia T, Moio N, Cavuto L, Sibilio G, Iardino MR, Di Carluccio C, Capaldo B. Glomerular filtration rate and cardiometabolic risk in an outpatient pediatric population with high prevalence of obesity. Obesity (Silver Spring) 2014; 22:585-9. [PMID: 23616281 DOI: 10.1002/oby.20497] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 03/27/2013] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To evaluate the relationship between estimated glomerular filtration rate (eGFR) and cardiometabolic risk factors (CMRF) in an outpatient pediatric population with high prevalence of obesity. DESIGN AND METHODS eGFR was evaluated in 901 children unselected for chronic kidney disease of whom 694 were overweight/obese (6-16 years) and 207 were age- and sex-matched normal weight (NW). We generated three categories of eGFR: mild-low eGFR (< 20th percentile), high eGFR (>80th percentile) and intermediate eGFR (20-80th percentile), considered as the reference category RESULTS Children with either mild-low or high eGFR category showed a 2-4 fold higher Odds ratio of high blood pressure, left ventricular hypertrophy, and microalbuminuria compared with children of the intermediate eGFR category. In addition, children with mild-low eGFR levels showed a 1.5-2 fold higher Odds ratio of impaired fasting glucose and high white blood cell count compared with children with intermediate eGFR levels. CONCLUSIONS In outpatient children with high prevalence of obesity, children with either mildly reduced or high eGFR have an increased burden of CMRF. Children with eGFR < 97 mL/min/1.73 m² show a worse CMR profile. This finding supports the usefulness to assess eGFR to identify children with unfavorable CMR profile.
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Radhakishun NNE, van Vliet M, von Rosenstiel IA, Beijnen JH, Diamant M. Limited value of routine microalbuminuria assessment in multi-ethnic obese children. Pediatr Nephrol 2013; 28:1145-9. [PMID: 23503768 DOI: 10.1007/s00467-013-2451-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 02/11/2013] [Accepted: 02/22/2013] [Indexed: 01/12/2023]
Abstract
BACKGROUND To determine the prevalence of microalbuminuria and its association with cardiometabolic risk factors in a multi-ethnic cohort of overweight and obese children. CASE-DIAGNOSIS/TREATMENT A retrospective analysis of prospectively collected data was performed using data from 408 overweight and obese children (age 3-19 years). In addition to administering an oral glucose tolerance test, we measured anthropometric variables, plasma lipid levels, alanine aminotransferase and the urinary albumin/creatinine ratio (ACR). Microalbuminuria was defined as an ACR of between 2.5 and 25 mg/mmol in boys and 3.5 and 25 mg/mmol in girls. In total, only 11 (2.7 %) of the children analyzed presented with microalbuminuria, with no differences between ethnic groups, sex or in the prevalence of hypertension compared to the children with normoalbuminuria. After adjustment for confounders, the body mass index Z-score tended to be different between the group with microalbuminuria versus that without (3.6 vs. 3.2, respectively; P = 0.054). ACR was not associated with hypertension, impaired glucose tolerance, high triglycerides or low high-density lipoprotein-cholesterol. CONCLUSIONS In a large multi-ethnic cohort of overweight and obese children, we found a low prevalence of microalbuminuria (11 children, 2.7 %), and in this small number of individuals, we found no association with any of the cardiometabolic risk factors assessed. Therefore, our data do not support the routine measurement of microalbuminuria in asymptomatic overweight and obese children and adolescents.
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Affiliation(s)
- Nalini N E Radhakishun
- Department of Pediatrics, Slotervaart Hospital, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands.
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Loffredo L, Martino F, Carnevale R, Pignatelli P, Catasca E, Perri L, Calabrese CM, Palumbo MM, Baratta F, Del Ben M, Angelico F, Violi F. Obesity and hypercholesterolemia are associated with NOX2 generated oxidative stress and arterial dysfunction. J Pediatr 2012; 161:1004-1009. [PMID: 22727869 DOI: 10.1016/j.jpeds.2012.05.042] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2012] [Revised: 05/01/2012] [Accepted: 05/18/2012] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To analyze the interplay among oxidative stress, NOX2, the catalytic core of nicotinamide-adenine dinucleotide phosphate oxidase, and endothelial dysfunction in children with obesity and/or hypercholesterolemia. STUDY DESIGN We performed a cross-sectional study comparing flow-mediated arterial dilation (FMD), oxidized low-density lipoprotein, and urinary excretion of isoprostanes (8-iso-PGF2α), as markers of oxidative stress, and NOX2 activity, as assessed by blood levels of soluble NOX2-dp (sNOX2-dp), in a population of 100 children, matched for age and sex, including 40 healthy subjects (HS), 20 children with hypercholesterolemia (HC), 20 obese children (OC), and 20 children with coexistence of hypercholesterolemia and obesity (HOC). RESULTS HOC had higher sNOX2-dp and oxidized low-density lipoprotein levels compared with HS, HC, and OC. HC, OC, and HOC had lower FMD values compared with HS. Urinary 8-iso-PGF2α excretion was higher in HOC compared with HS. FMD was inversely correlated with sNOX2-dp levels (r = -0.483; P < .001) and with the number of cardiovascular risk factors (r = -0.617; P < .001). Multiple linear regression analysis showed that the number of cardiovascular risk factors was the only independent predictive variable associated with FMD (β: -0.585; P < .001; R(2) = 35%) and sNOX2-dp (β: 0.587; P < .001; R(2) = 34%). CONCLUSION The study suggests that NOX2-generating oxidative stress may have a pathogenic role in the functional changes of the arterial wall occurring in HOC.
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Nerpin E, Helmersson-Karlqvist J, Risérus U, Sundström J, Larsson A, Jobs E, Basu S, Ingelsson E, Arnlöv J. Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study. BMC Res Notes 2012; 5:537. [PMID: 23016573 PMCID: PMC3527356 DOI: 10.1186/1756-0500-5-537] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2012] [Accepted: 09/22/2012] [Indexed: 01/02/2023] Open
Abstract
Background The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men. Findings Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2α [PGF2α]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years). Results In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (β-coefficient −0.13 to −0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (β-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (β- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (β-coefficient −0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR. Conclusion Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.
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Affiliation(s)
- Elisabet Nerpin
- Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, SE- 751 85, Uppsala, Sweden.
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Brill MJE, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CAJ. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet 2012; 51:277-304. [PMID: 22448619 DOI: 10.2165/11599410-000000000-00000] [Citation(s) in RCA: 277] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The prevalence of obesity in adults and children is rapidly increasing across the world. Several general (patho)physiological alterations associated with obesity have been described, but the specific impact of these alterations on drug metabolism and elimination and its consequences for drug dosing remains largely unknown. In order to broaden our knowledge of this area, we have reviewed and summarized clinical studies that reported clearance values of drugs in both obese and non-obese patients. Studies were classified according to their most important metabolic or elimination pathway. This resulted in a structured review of the impact of obesity on metabolic and elimination processes, including phase I metabolism, phase II metabolism, liver blood flow, glomerular filtration and tubular processes. This literature study shows that the influence of obesity on drug metabolism and elimination greatly differs per specific metabolic or elimination pathway. Clearance of cytochrome P450 (CYP) 3A4 substrates is lower in obese as compared with non-obese patients. In contrast, clearance of drugs primarily metabolized by uridine diphosphate glucuronosyltransferase (UGT), glomerular filtration and/or tubular-mediated mechanisms, xanthine oxidase, N-acetyltransferase or CYP2E1 appears higher in obese versus non-obese patients. Additionally, in obese patients, trends indicating higher clearance values were seen for drugs metabolized via CYP1A2, CYP2C9, CYP2C19 and CYP2D6, while studies on high-extraction-ratio drugs showed somewhat inconclusive results. Very limited information is available in obese children, which prevents a direct comparison between data obtained in obese children and obese adults. Future clinical studies, especially in children, adolescents and morbidly obese individuals, are needed to extend our knowledge in this clinically important area of adult and paediatric clinical pharmacology.
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Affiliation(s)
- Margreke J E Brill
- Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, the Netherlands
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Arimura E, Horiuchi M, Kawaguchi H, Miyoshi N, Aoyama K, Takeuchi T. Low-protein diet improves blood and urinary glucose levels and renal manifestations of diabetes in C57BLKS-db/db mice. Eur J Nutr 2012; 52:813-24. [PMID: 22692501 DOI: 10.1007/s00394-012-0387-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2012] [Accepted: 05/22/2012] [Indexed: 12/17/2022]
Abstract
PURPOSE Dietary protein content is related clinically to the development of diabetic nephropathy. Here, we investigated how dietary protein content (12-24 % energy) within the range used by humans affected renal manifestations including the expressions of genes involved in the renin-angiotensin (RA) system in control and diabetic mice. Moreover, we examined the effects of dietary protein content on HbA1c and urinary glucose. METHODS Control (CT) and leptin receptor-deficient obese (db) mice, 5 weeks old, were fed the diets below. Under ad libitum conditions, mice were fed 12, 18, and 24 % energy from protein (L-, M-, and H-diets) for 8 weeks. Under pair-feeding conditions, db mice were supplied H-diet (db-Hp) to the equivalent energy to that consumed by db-L mice. Renal manifestations and values related to glucose and insulin were examined biochemically and pathologically. RESULTS Under ad libitum conditions, db mice consumed food and water dose dependently of the dietary protein content, although they were consumed similarly by CT mice. CT-L mice showed lower urinary albumin and kidney weight, in association with lower mRNA levels of angiotensinogen and renin, than CT-H mice. Under pair-feeding conditions, db-L mice showed a lower ratio of kidney/body weight, HbA1(C), and urinary glucose, and a higher β-cell distribution rate in the pancreas than db-Hp mice. CONCLUSIONS Low-protein intake in the range used by humans may relieve renal manifestations through the suppressed expression of genes in the renal RA system of CT mice. On the other hand, in db mice, low-protein intake improved hyperglycemia and the renal manifestations of diabetes.
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Affiliation(s)
- Emi Arimura
- Department of Life and Environmental Science, Kagoshima Prefectural College, Kagoshima, Japan
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Giannini C, D'Adamo E, de Giorgis T, Chiavaroli V, Verrotti A, Chiarelli F, Mohn A. The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood. Pediatr Nephrol 2012; 27:269-75. [PMID: 21870072 DOI: 10.1007/s00467-011-1988-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Revised: 08/04/2011] [Accepted: 08/05/2011] [Indexed: 12/23/2022]
Abstract
The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.
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Affiliation(s)
- Cosimo Giannini
- Department of Pediatrics, University of Chieti, Via dei Vestini 5, 66100, Chieti, Italy
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