Role of urinary NGAL and KIM-1 as biomarkers of early kidney injury in obese prepubertal children

2020 ◽  
Vol 33 (9) ◽  
pp. 1183-1189 ◽  
Author(s):  
Nella Polidori ◽  
Cosimo Giannini ◽  
Roberta Salvatore ◽  
Piernicola Pelliccia ◽  
Adriana Parisi ◽  
...  

AbstractObjectivesChildhood 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.MethodsWe 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.ResultsTriglycerides, 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.ConclusionsThese findings suggest that obese subjects exhibit a certain degree of renal damage before kidney function loss.

2018 ◽  
Vol 51 (5) ◽  
pp. 293-296 ◽  
Author(s):  
Arine Santos Peçanha ◽  
Alexandra Maria Monteiro ◽  
Fernanda Mussi Gazolla ◽  
Isabel Rey Madeira ◽  
Maria Alice Neves Bordallo ◽  
...  

Abstract Objective: To evaluate, using ultrasound, the distribution of abdominal fat in obese prepubertal children, as well as its possible correlation with metabolic changes due to obesity. Materials and Methods: This was a cross-sectional study of prepubescent children: 77 obese children (33 girls and 44 boys), with a mean age of 7.31 years; and 31 normal-weight children (17 girls and 14 boys), with a mean age of 7.32 years. In all of the children, abdominal wall thickness (AWT) and abdominal fat thickness (AFT) were measured by ultrasound. For the evaluation of the associated metabolic alterations, serum levels of glycemia, HDL cholesterol, triglycerides, and insulin were determined. Results: The obese children presented with greater abdominal fat, predominantly greater AWT, without a significant gender-related difference in AWT or AFT. The homeostasis model assessment of insulin resistance (HOMA-IR) showed a significant direct correlation with AWT and AFT. Conclusion: In obese prepubertal children, the AWT, as measured by ultrasound, was shown to be more closely related to the HOMA-IR than to the lipid metabolism or glycemia.


2019 ◽  
Vol 74 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Ting Chen ◽  
Fengyun Wang ◽  
Zhenyu Chu ◽  
Ling Sun ◽  
Haitao Lv ◽  
...  

Objectives: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. Method: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. Results: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. Conclusions: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.


2018 ◽  
Vol 31 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Paola Di Filippo ◽  
Alessandra Scaparrotta ◽  
Daniele Rapino ◽  
Tommaso de Giorgis ◽  
Marianna Immacolata Petrosino ◽  
...  

AbstractBackground:Recent findings have supposed that the underlying association between the increased prevalence of both asthma and obesity may be insulin resistance (IR).Methods:Insulin and glucose serum levels were analyzed to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) for IR in 98 pre-pubertal children. Lung function and allergy status evaluation were performed. The study population was divided into four groups: (1) obese asthmatic children (ObA); (2) normal-weight asthmatic children (NwA); (3) normal-weight non-asthmatic children (Nw) and (4) obese non-asthmatic children (Ob).Results:Forced expiratory volume in 1 s (FEV1) was slightly lower in obese subjects compared with normal-weight subjects and forced vital capacity (FVC) appeared lower in asthmatics, whereas between non-asthmatics subjects, it was lower in the obese group than in the normal-weight one. The post hoc analysis revealed a statistically significant reduction in FEV1, peak expiratory flow (PEF), forced expiratory flows (FEF) between 50% and 25% of the FVC (FEF50and FEF25) between ObA and Nw and in FEV1, FVC, PEF, FEF50and FEF25between NwA and Nw, but no statistically significant differences of lung function parameters were observed between ObA and NwA. We found an inverse relationship between HOMA-IR and all spirometric parameters, although without any statistical significance. We also observed a significantly lower FVC in insulin-resistant children (HOMA-IR>95th percentile) (p=0.03).Conclusions:This study suggests that lung function could be early altered in obese children, already in pre-pubertal age. Although IR should not manifest its effects on lungs in pre-pubertal obese children, the prevention or treatment of obesity in the pre-pubertal period may prevent definitive negative effects on lungs.


2016 ◽  
Vol 116 (5) ◽  
pp. 805-815 ◽  
Author(s):  
Liane Correia-Costa ◽  
Teresa Sousa ◽  
Manuela Morato ◽  
Dina Cosme ◽  
Joana Afonso ◽  
...  

AbstractOxidative 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), Pfor 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.


2007 ◽  
Vol 99 (4) ◽  
pp. 909-917 ◽  
Author(s):  
M. Gil-Campos ◽  
E. Larqué ◽  
M. C. Ramírez-Tortosa ◽  
J. Linde ◽  
I. Villada ◽  
...  

Obese patients typically show a pattern of dyslipidaemia and changes in plasma fatty acid composition reflecting abnormalities in lipoprotein metabolism and dietary habits. Animals and obese adults have been widely studied; however, contradictory results have been published in children. The objective was to assess changes in plasma fatty acid composition in total plasma lipids and plasma lipid fractions in obese prepubertal children compared with those of normal weight and to evaluate changes in postprandial plasma fatty acids during a 3 h period after intake of a standardised breakfast. The study was a case–control study with thirty-four obese and twenty normal-weight prepubertal children (Tanner 1). Anthropometric and metabolic variables and fatty acid concentrations were measured in plasma and its fractions. Liquid chromatography was used to separate lipid fractions and GLC to quantify fatty acids. Plasma total fatty acids (TFA), SFA, MUFA and PUFA concentrations were higher in obese than in control children. Except for 18 : 0, 18 : 3n-3, 20 : 4n-6 and n-3 PUFA, all fatty acids in TAG were also elevated in the obese group. Fatty acids 16 : 1n-7, 18 : 0, 18 : 1n-9, 20 : 2n-6, TFA and MUFA significantly decreased between the 2nd and 3rd hour in normal-weight v. obese children. The concentration of 16 : 1n-7 was positively and the proportion of 20 : 4n-6 inversely associated with a significant increase in risk of obesity. Obese prepubertal children show an altered plasma fatty acid profile and concentrations, mainly related to the TAG fatty acid profile, with a lower clearance of fatty acids v. normal-weight prepubertal children.


2009 ◽  
Vol 161 (6) ◽  
pp. 861-870 ◽  
Author(s):  
Lucia Pacifico ◽  
Eleonora Poggiogalle ◽  
Francesco Costantino ◽  
Caterina Anania ◽  
Flavia Ferraro ◽  
...  

BackgroundGhrelin, a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity. Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms, and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined.ObjectiveWe investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values.DesignA total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined. IR was determined by a homeostasis model assessment (HOMA) of IR.ResultsIn the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects. Compared with lean healthy children, lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS.ConclusionsA-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS.


2013 ◽  
Vol 305 (5) ◽  
pp. R552-R557 ◽  
Author(s):  
Christian K. Roberts ◽  
Ali Izadpanah ◽  
Siddhartha S. Angadi ◽  
R. James Barnard

Lifestyle intervention programs currently emphasize weight loss secondary to obesity as the primary determinant of phenotypic changes. We examined whether the effects of a short-term lifestyle intervention program differ in normal-weight versus overweight/obese children. Nineteen overweight/obese (O; BMI = 33.6 ± 1.9 kg/m2) and 14 normal-weight (N; BMI = 19.9 ± 1.5 kg/m2) children participated in a 2-wk program consisting of an ad libitum high-fiber, low-fat diet and daily exercise (2–2.5 h). Fasting serum samples were taken pre- and postintervention for determination of lipids, glucose homeostasis, inflammatory cytokines, and adipokines. Only the O group lost weight (3.9%) but remained overweight/obese (32.3 ± 1.9 kg/m2). Both groups exhibited significant intervention-induced decreases ( P < 0.05) in serum insulin (N: 52.5% vs. O: 28.1%; between groups, P = 0.38), homeostatic model assessment for insulin resistance (N: 53.1% vs. O: 28.4%, P = 0.43), leptin (N: 69.3% vs. O: 44.1%, P = 0.10), amylin (N: 28.7% vs. O: 26.1%, P = 0.80), resistin (N: 40.0% vs. O: 35.1%, P = 0.99), plasminogen activator-inhibitor-1 (N: 30.8% vs. O: 25.6%, P = 0.59), IL-6 (N: 58.8% vs. O: 48.5%, P = 0.78), IL-8 (N: 46.0% vs. O: 42.2%, P = 0.49), and TNFα (N: 45.8% vs. O: 40.8%, P = 0.99). No associations between indices of weight change and phenotypic changes were noted. A short-term, intensive lifestyle modification program is effective in ameliorating metabolic risk factors in N and O children. These results suggest that obesity per se was not the primary driver of the phenotypes noted and that dietary intake and physical inactivity induce the phenotypic abnormalities. These data may have implications for the weight loss-independent management of cardiometabolic risk in pediatric populations.


2020 ◽  
Author(s):  
Chunyan Yin ◽  
hong ai zhang ◽  
Meizheng Zhang ◽  
yanfeng y xiao

Abstract Objective Metabolic syndrome (MetS) is the most extensively described condition associated with childhood and adolescent obesity and is a challenging public health issue. Studies regarding the specificity and sensitivity of serum levels of adropin and apelin -12 as predictors of MetS are limited. The aim was to evaluate the prospective association between adropin and apelin -12 concentrations and MetS and sensitivity as predictors of MetS in the obese children. Methods This study involved 138 children. The study group included obese subjects with MetS and the two control groups included obese without MetS and normal weight subjects. Anthropometric parameters and clinical data were collected. Plasma levels of apelin -12, adropin, leptin, adiponectin and TNF-α were measured. Results Obese children with MetS had significantly higher levels of apelin -12 and significantly lower levels of adropin compared to those without MetS. In logistic regressions, we identified that apelin -12 was risk factor for metabolic syndrome and adropin was the protecting factors of having MetS after adjustment for age, sex and puberty. Furthermore, adropin and apelin -12 are two more sensitive predictors of metabolic syndrome than leptin and adiponect using ROC method. Conclusion Serum adropin and apelin -12 levels can be useful biomarkers for evaluation of the risk of MetS in obese children. This may provide a novel approach for treatment or prevention of MetS development.


2007 ◽  
Vol 156 (4) ◽  
pp. 497-502 ◽  
Author(s):  
Miguel Valle Jiménez ◽  
Rosario Martos Estepa ◽  
Rosario MaMorales Camacho ◽  
Ramón Cañete Estrada ◽  
Félix Gascón Luna ◽  
...  

Background: The metabolic syndrome (MS) is associated with insulin resistance (IR), a systemic low-grade inflammatory state and endothelial dysfunction. These disorders may arise at a very early age in obese children. This study aimed to investigate the relationship between endothelial dysfunction and both IR and inflammation in prepubertal obese children. Methods and results: Von Willebrand factor (vWF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured in 46 obese prepubertal children aged 6–9, and in 46 non-obese, age-and sex-matched controls; the possible association of these levels with MS, various inflammatory biomarkers and plasminogen activator inhibitor-1 (PAI-1) was analyzed. Obese children displayed significantly elevated values for sICAM-1 (P = 0.008), vWF (P = 0.034), insulin (P = 0.006), homeostasis model assessment for IR (HOMA-IR; P = 0.003), C-reactive protein (CRP) (P < 0.001), PAI-1 (P = 0.002) and leptin (P < 0.001). Nonsignificant differences were found in interleukin 6 (IL-6) levels. In the obese group, sICAM-1 showed a positive correlation with insulin (P = 0.013), HOMA-IR (P = 0.015), CRP (P = 0.020), IL-6 (P = 0.023) and PAI-1 (P = 0.015). Corrected for age and sex, insulin, HOMA-IR, IL-6 and CPR were found to be independent predictive factors for sICAM-1. Conclusions: Prepubertal obese children displayed alterations indicative of endothelial dysfunction as well as disorders typical of MS. An association was established between endothelial dysfunction, IR, inflammation and inappropriate fibrinolysis in the children studied.


2020 ◽  
Author(s):  
yanfeng xiao ◽  
hong ai zhang ◽  
mei zhen zhang ◽  
chunyan yin

Abstract Background: Metabolic syndrome (MetS) is the most extensively described condition associated with childhood and adolescent obesity and is a challenging public health issue. Studies regarding the specificity and sensitivity of serum levels of adropin and apelin -12 as predictors of MetS are limited. The aim was to evaluate the prospective association between adropin and apelin -12 concentrations and MetS and sensitivity as predictors of MetS in the obese children.Methods:: This study involved 138 children. The study group included obese subjects with MetS and the two control groups included obese without MetS and normal weight subjects. Anthropometric parameters and clinical data were collected. Plasma levels of apelin -12, adropin, leptin, adiponectin and TNF-α were measured. Results: Obese children with MetS had significantly higher levels of apelin -12 and significantly lower levels of adropin compared to those without MetS. In logistic regressions, we identified that apelin -12 was risk factor for metabolic syndrome and adropin was the protecting factors of having MetS after adjustment for age, sex and puberty. Furthermore, adropin and apelin -12 are two more sensitive predictors of metabolic syndrome than leptin and adiponect using ROC method. Conclusion: Serum adropin and apelin -12 levels can be useful biomarkers for evaluation of the risk of MetS in obese children. This may provide a novel approach for treatment or prevention of MetS development.


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