Neutrophil gelatinase-associated lipocalin and Cathepsin L as early predictors of kidney dysfunction in children with type 1 diabetes.

INTRODUCTION: The aim of this study was to evaluate serum levels and urinary excretion of neutrophil-gelatinase associated lipocalin (respectively sNGAL and uNGAL) and urinary excretion of Cathepsin L (uCathL) in children with type 1 diabetes mellitus (DM1) who presented normoalbuminuria and the estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73 m2. MATERIAL AND METHODS: The study group consisted of 63 children with a diabetes duration of 5.16 ± 3.39 years. The degree of albuminuria was based on urine albumin-to-creatinine ratio (ACR), while eGFR was based on serum cystatin C. Glomerular hyperfiltration (GH) was defined as an eGFR value above 135 mL/min/1.73 m2. RESULTS: Children with DM1 showed significantly higher concentrations of uNGAL, and lower sNGAL and uCathL. Significant changes of uNGAL and uCathL levels were even found in children without GH and with optimal glycaemic control (HbA1c < 7.5%). Positive correlations between uNGAL, ACR and eGFR were shown, as well as between uCathL and eGFR. CONCLUSIONS: Significant changes in the concentration of markers of early kidney injury: sNGAL, uNGAL, and uCathL, can occur in children with DM1 and normoalbuminuria. The changes of uNGAL and uCathL can be even found in children without GH and with optimal glycaemic control. The earliest signs of diabetic kidney dysfunction seem to result from tubular damage.

Polymorphisms in 5'-flanking regions of genes encoding adiponectin, leptin, and resistin are not associated with obesity of Polish children and adolescents.

Genes encoding adipokines are important functional candidates for development of obesity. In this study we screened for polymorphism 5'-flanking regions of the adiponectin (ADIPOQ), leptin (LEP) and resistin (RETN) genes in a cohort of Polish obese children and adolescents (n = 243) and a control group of non-obese adults (n = 100). Altogether 13 SNPs (single nucleotide polymorphisms) and 1 InDel (insertion/deletion polymorphism) were found. Among them five polymorphisms, localized in the LEP gene, turned out to be novel, but their distribution was insufficient for association studies. We found no consistent evidence for association between obesity and the SNPs demonstrating minor allele frequency (MAF) above 0.2 (ADIPOQ: -11377C>G, LEP: -2548C>T, 19A>G, RETN: -1300G>A, -1258C>T, -420C>G). Comparison of polymorphisms distribution in patients and control group suggested association with ADIPOQ -11377C>G (Pearson test P = 2.76 × 10(-11)), however, we did not observe any effect of this polymorphism on BMI or relative BMI (RBMI) within obese patients (P = 0.41). We conclude that the tested SNPs are not useful markers of childhood and adolescence obesity in Polish population.

Normal-range albuminuria does not exclude nephropathy in diabetic children.

Clinically detectable diabetic nephropathy (DN) begins with the development of microalbuminuria (MA). However, early renal dysfunction may be overlooked despite using that method. On the other hand, the gold standard in DN detection-that is, renal biopsy-is highly invasive. The aim of this study was to evaluate the level of neutrophil-gelatinase-associated lipocalin (NGAL) and interleukin (IL)-18 and their relations to albumin excretion rate (AER) in children with normal-range albuminuria, e.g. in those considered as not presenting diabetic nephropathy. The study group consisted of 22 children (age 12.7 +/- 3.5 years) with type 1 diabetes mellitus (T1DM). Long-term glycemic control was assessed on hemoglobin A1c (HbA1c) levels (8.52 +/- 1.78%). All patients presented normal estimated glomerular filtration rate (eGFR) (141 +/- 23 ml/min/1.73 m(2)) and normal urinary albumin excretion (13.09 +/- 7.63 mg/24 h). Fourteen healthy children served as a control group. Children with T1DM showed increased NGAL values with respect to controls-interestingly, both in serum (sNGAL) (867.43 +/- 341.98 vs. 655.29 +/- 196.17 ng/ml; p = 0.04) and in urine (uNGAL) (420.04 +/- 374.16 vs. 156.53 +/- 185.18 ng/ml, p = 0.04). IL-18 levels were not different in both groups both in serum (58.52 +/- 20.11 vs. 69.79 +/- 58.76 ng/ml; NS) and in urine (14.53 +/- 12.74 vs. 14.60 +/- 10.92 ng/ml; NS). Despite the relatively small study group, the positive correlation between sNGAL and AER was found [AER (mg/24 h) = 3.1893 + 0.01141 x sNGAL (ng/ml); r = 0.51; p = 0.014] as well as between uNGAL and AER [AER (mg/24 h) = 8.7538 + 0.01032 x uNGAL (ng/ml); r = 0.51; p = 0.016]. No relationship between sNGAL and uNGAL, and GFR and HbA1c were found. Normal-range albuminuria does not exclude diabetic nephropathy defined as increased sNGAL and uNGAL concentration. NGAL measurement can be more sensitive than MA and may become a useful tool for evaluating renal involvement in diabetic children.