Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration

Abstract

Background: The pathogenesis of diabetic kidney disease (DKD) is complex and involves both glomerular and tubular dysfunction. A global assessment of kidney function is necessary to stage DKD, a progressive kidney disease that is likely to begin in childhood. The present study evaluated whether kidney injury biomarkers identified as early DKD biomarkers in adults have any prognostic value in the very early stages of childhood diabetes.

Methods: We measured urine free Retinol-binding protein 4 (UfRBP4), albumin (UAlb), Kidney injury molecule-1 (KIM-1) and the microRNAs miR-155, miR-126 and miR-29b in two cohorts of paediatric T1DM patients without evidence of DKD, but with diabetes of short-duration, ≤ 2.5 years (SD, n = 25) or of long-duration, ≥ 10 years (LD, n = 29); non-diabetic siblings (H, n = 26) were recruited as controls. A p value < 0.05 was considered significant for all results.

Results: UfRBP4 and UAlb were not significantly different across the three groups. No differences were found in KIM-1 excretion between any of the three groups. UfRBP4 was correlated with UAlb in all three groups (r 0.49; p < 0.001), whereas KIM-1 showed no correlation with albumin excretion. Among microRNAs, miR-29b was higher in all diabetic children compared with the H control group (p = 0.03), whereas miR-155 and miR-126 were not significantly different. No differences were found between the SD and LD groups for all three microRNAs. No associations were identified between these biomarkers with sex, age, BMI, eGFR, T1DM duration or glycaemic control.

Conclusions: UfRBP4, KIM-1, miR-155, and miR-126 were unaffected by the presence and duration of diabetes, whereas miR-29b showed a modest elevation in diabetics, regardless of duration. These data support the specificity of a panel of urine biomarkers as DKD biomarkers, rather than any relationship to diabetes per se or its duration, and not as early DKD biomarkers in a paediatric setting.

Keywords: Albuminuria; Diabetic kidney disease; Kidney injury molecule-1; Type 1 diabetes mellitus; Urinary biomarkers; Urine free retinol-binding protein 4; microRNAs.

Fig. 1

Patient recruitment and distribution into the different study groups

Fig. 2

UfRBP4 and KIM-1 across the study groups. Both biomarkers were not significantly different across children with or without T1DM

Fig. 3

Expression of miR-126, miR-29b and miR-155 in healthy children compared to diabetic children (SD and LD groups). miR-29b was higher in diabetic children overall compared to controls (*p = 0.03), whereas miR-155 and miR-126 were similar across the two groups

Fig. 4

Relationship between UfRBP4 and Ualb across all study groups. UfRBP4 urine free retinol-binding protein 4 (µg/mmol); Ualb urinary albumin expressed as albumin to creatinine ratio (mg/mmol)