Background: Childhood obesity is one of the most important causes of end-stage renal disease. The onset of obesity-associated renal disease is insidious and asymptomatic. To date available markers do not perfectly mimic kidney injury and may not characterize kidney changes especially in early stages and of renal tubulointerstitium. Tubular changes (KIM-1 and NGAL) are already apparent before the onset of proteinuria or alterations of GFR and thus might represent biomarker that directly reflects kidney injury and which are easily measured from urine, facilitating a direct monitoring of kidney damage early in the course of the disease.
Methods: Therefore we aimed to characterize kidney injury in a group of 40 obese prepubertal children (22 Male/18 Female; 9.7±1.9 years) compared to 40 healthy prepubertal age- and gender matched peers (18 Male/22 Female; 9.6±2.2 years). Anthropometric measurements and body composition were determined. Fasting blood samples were collected for measurement of insulin, glucose, lipid profile, ALT, AST, Cystatin C and creatinine (Scr). Urine samples were collected to assess urinary NGAL and KIM-1 and for the evaluation of 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 performed to explore any relationship between variables.
Results: Triglycerides, ALT, glucose, insulin, HOMA-IR and Cystatin C values were significantly higher while HDL cholesterol levels were significantly lower in obese children than normal weight peers. No difference was documented in terms of total cholesterol and LDL cholesterol between the two groups. Scr values were all within normal limits and all patients had normal GFR without significant differences between the two groups. We showed that obese children had larger kidney sizes compared to healthy subjects, indicating organ hypertrophy. NGAL and KIM-1 are increased in obese children with normal kidney function. We documented a significant association between both NGAL and KIM-1 with adiposity indices, insulin status and markers of oxidative stress suggesting a possible obesity effect in inducing kidney abnormalities. In addition, KIM-1 and NGAL are directly related respectively to Cystatin C, isoprostanes and kidney length, supporting the ability of these biomarkers in reflecting early kidney damages in obese subjects.
Conclusions: These findings postulate that obese subjects exhibit a certain degree of renal damage before kidney function loss and it seems to confirm the hypothesis that the tubular phase of damage precedes the manifestations of classic glomerular lesions.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology