Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity.

BACKGROUND AND AIMS: Glomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown. METHODS AND RESULTS: Cross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m2. Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (-12%), NEFA (-26%) and uric acid (-22%) than those without GH (all p < 0.05). Similarly to high sensitivity C-reactive protein (hsCRP), there were no differences in serum chemokines between children with GH or not (all p > 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = -0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05). CONCLUSION: GH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings.

Different alterations of glomerular filtration rate and their association with uric acid in children and adolescents with type 1 diabetes or with overweight/obesity.

BACKGROUND: Hyperfiltration (HF) occurs early in diabetes or obesity (OB)-associated renal disease. Alterations of glomerular filtration rate (GFR) in childhood OB remain unclear. OBJECTIVES: To compare the prevalence of GFR alterations and its association with uric acid in children and adolescents with type 1 diabetes (T1D) vs overweight (OW)/OB. METHODS: Cross-sectional study of 29 youths (aged: 13 ± 2 years) with T1D (disease duration: 7 ± 3 years) and 165 with OW/OB (aged: 11 ± 3 years). Patients with an albumin-creatinine ratio >3.39 mg/mmol were excluded. GFR was estimated with creatinine-cystatin C Zappitelli equation. HF and low GFR were defined by a GFR > 135 and <90 mL/min.1.73 m2 , respectively. RESULTS: HF was higher in children with T1D vs OW/OB (28% vs 10%, P < .005). Children with OW/OB also showed a 10% of low GFR. In patients with T1D, HbA1c (ß = .8, P < .001), and systolic blood pressure (ß = 11.4, P < .005) were independent predictors of GFR (R2 = .65). In OW/OB, HF cases were almost limited to prepubertal children and low GFR to pubertal ones. GFR in OW/OB was associated with age (ß = -2.2, P < .001), male sex (ß = -11.6, P < .001), and uric acid (ß = -.05, P < .001) in adjusted models (R2 = .33). CONCLUSIONS: GFR alterations were different between youths with T1D and with OW/OB. Higher uric acid, older age, and puberty were related to lower GFR values in OW/OB children. Longitudinal studies will determine if low GFR is consequence of a rapid GFR decline in pediatric patients with OW/OB.