The effect of obesity and type 1 diabetes on renal function in children and adolescents.

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.

US in the diagnosis of gastroesophageal reflux in children.

Several techniques have been used to diagnose gastroesophageal reflux (GER) in children, but no single test is sufficiently accurate to completely investigate the problem. Gastroesophageal US has been described as a widely available, noninvasive and sensitive method. It provides morphological and functional information, but its role in the diagnosis of GER in children is still debated. In this paper we review diagnostic approaches to GER in children. We focus on current use of US in the management of children with suspected GER. Reports suggest that US allows exclusion of several non-GER causes of symptoms and that it provides morphological and functional data with high sensitivity and positive predictive value for the diagnosis of GER. Sonographic assessment of findings such as abdominal esophageal length, esophageal diameter, esophageal wall thickness and gastroesophageal angle provide important diagnostic indicators of reflux and related to the degree of GER. There is a need for standardization of the procedure and for defining diagnostic criteria.

Implications for kidney disease in obese children and adolescents.

Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears.

Clinical practice guidelines: what they are, why we need them and how they should be developed through rigorous evaluation.

The number of available clinical practice guidelines has grown enormously in the recent years, therefore requiring a correct approach and use of them. We present a revision of what guidelines are and serve, how to correctly develop and find them, and how to develop and evaluate them through rigorous scientific methods. Limits and benefits of guidelines are also discussed. An overview about the use of paediatrics' guidelines is finally reported.

Early changes in renal hemodynamics in children with diabetes: Doppler sonographic findings.

PURPOSE: Although clinically evident diabetes-related microvascular complications are extremely rare in childhood, early functional and structural abnormalities may be present a few years after the onset of the disease. Renal Doppler resistance index (RI) is widely used for the evaluation of blood flow in renal parenchymal diseases. This study was designed to investigate the possible alteration of intrarenal Doppler RI in children with diabetes compared with healthy children. METHODS: The study was performed in 42 children with diabetes (age range, 6-18 years) and in 41 age-matched healthy controls, all having normal renal function. RI was measured with Doppler sonography in interlobular renal arteries. RESULTS: RI values were significantly greater in children with diabetes than in age-matched healthy controls (0.64 +/- 0.03 versus 0.60 +/- 0.04, P < 0.035). RI correlated positively with HbA1c (P < 0.001, r = 0.42) and diabetes duration (P < 0.05, r = 0.39). CONCLUSION: Early changes in renal hemodynamics are detectable on Doppler sonography in children with diabetes without any evidence of renal dysfunction and may suggest a preclinical stage of diabetic nephropathy.

Serum and urinary nitrites and nitrates and Doppler sonography in children with diabetes.

OBJECTIVE: The aim of the present study was to evaluate serum and urinary nitric oxide (NO) concentrations in children and adolescents with diabetes compared with age-matched healthy control subjects to find out whether Doppler ultrasonography could be used to detect changes in renal resistive indexes (RIs) in children with diabetes and to assess whether there are correlations between these parameters and NO excretion. RESEARCH DESIGN AND METHODS: We studied 42 children with type 1 diabetes and 41 matched healthy control subjects, both divided into prepubertal or pubertal children. Serum and urinary nitrite and nitrate (NO2-+NO3-) concentrations were evaluated as an index of NO production. Doppler ultrasonographic registration of intrarenal RI was performed. RESULTS: Compared with healthy control subjects, children with diabetes had significantly increased concentrations of serum (30.26 +/- 6.52 vs. 24.47 +/- 7.27 mmol/l, P = 0.001) and urinary NO2-+NO3- (345.07 +/- 151.35 vs. 245.86 +/- 80.25 mmol/l, P = 0.002); the same was true for Doppler RI values (0.64 +/- 0.03 vs. 0.60 +/- 0.04, P = 0.035). This occurs in both prepubertal and the pubertal children. A significant positive correlation was found between serum and urinary NO2-+NO3- levels (P = 0.002, r = 0.374). Serum NO2-+NO3- concentrations also correlated positively with Doppler RI (P = 0.032, r = 0.262) and HbA1c (A1C) (P = 0.004, r = 0.329); urinary NO2-+NO3- concentrations correlated positively with A1C (P = 0.001, r = 0.394). Doppler RI correlated positively with A1C (P = 0.000, r = 0.424). CONCLUSIONS: This study demonstrates that in children with diabetes, chronic hyperglycemia may act through a mechanism that involves increased NO production and/or action and contributes to generating intrarenal hemodynamic abnormalities, which are detectable by Doppler ultrasonography even in early diabetic nephropathy.

TNF-α gene polymorphisms and juvenile idiopathic arthritis: Influence on disease outcome and therapeutic response.

OBJECTIVE: To investigate the genetic contribution of TNF-α gene polymorphisms on the disease course and therapeutic response in patients with juvenile idiopathic arthritis (JIA). METHODS: 74 Caucasian patients with JIA were recruited with a control group of 77 healthy children. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at positions -163, -244, -238, -376, and -308. RESULTS: No SNPs at position -163 were observed, while we observed only SNPs at positions -244 and -376 in the controls. No differences were observed in the prevalence of SNPs at -238 and -308 between JIA and controls. In JIA patients no significant differences were observed between the -238 and -308 G/A genotypes and different disease phenotypes. We observed a significant lower disease activity expressed in the carriers of -308 GG genotype with respect to GA and AA genotypes after 6 (p = 0.008 and p = 0.013, respectively) and 12 months of disease (p = 0.02 and p = 0.08, respectively). Also the -238 GG genotypes showed a better disease course after 12 months of disease. Moreover, the -238/-308 GG genotypes presented the higher reduction of disease activity both after 6 (p < 0.01 vs GA and p < 0.01 vs AA) and 12 months from baseline (p < 0.01 vs GA and p < 0.01 vs AA). After 12 months of biologic therapy, a significant higher disease activity was observed in patients with genotype -308 AA respect to both GA (p = 0.012) and GG (p = 0.016). CONCLUSIONS: JIA patients carrying the TNF-α -308 GA/AA and -238 GA genotypes are associated with a worse prognosis and with a lower response to anti-TNF-α drugs.

Obesity-related renal injury in childhood.

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