Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes

Background Early identification of youth with type 1 diabetes (T1D) at risk for diabetic kidney disease may improve clinical outcomes. We examined the cross-sectional relationship between kidney biomarkers neutrophil gelatinase-associated lipocalin (NGAL), copeptin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), chitinase-3-like protein-1 (YKL-40), and monocyte chemoattractant protein-1 (MCP-1) and intrarenal hemodynamic function in adolescents with T1D. Methods Urine albumin-to-creatinine ratio (UACR), renal vascular resistance (RVR), glomerular filtration rate (GFR), intraglomerular pressure (P-GLO), efferent arteriole resistance (R-E), afferent arteriolar resistance (R-A), and renal plasma flow (RPF), and the above indicated biomarkers were assessed in youth aged 12-21 years with and without T1D of < 10 years duration. Results Fifty adolescents with T1D (16.1 +/- 3.0 years, HbA1c 8.6 +/- 1.2%) and 20 adolescents of comparable BMI without T1D (16.1 +/- 2.9 years, HbA1c 5.2 +/- 0.2%) were enrolled. Adolescents with T1D demonstrated significantly higher GFR, RPF, R-E, and P-GLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and R-A than controls (25% and 155%, respectively, both p < 0.0001). YKL-40 and KIM-1 concentrations, respectively, were positively associated with GFR (r: 0.43, p = 0.002; r: 0.41, p = 0.003), RPF (r: 0.29, p = 0.08; r: 0.34, p = 0.04), UACR (r: 0.33, p = 0.02; r: 0.50, p = 0.0002), and P-GLO (r: 0.45, p = 0.006; r: 0.52, p = 0.001) in adolescents with T1D. Conclusions Higher concentrations of biomarkers YKL-40 and KIM-1 may help define the risk for intraglomerular hemodynamic dysfunction in youth with T1D.

Automated summary

This study examined the relationship between kidney biomarkers and intrarenal hemodynamic function in adolescents with type 1 diabetes (T1D). The results showed that higher concentrations of biomarkers YKL-40 and KIM-1 were associated with higher glomerular filtration rate (GFR), renal plasma flow (RPF), and intraglomerular pressure (P-GLO) in adolescents with T1D. The study suggests that elevated concentrations of YKL-40 and KIM-1 may help define the risk for intraglomerular hemodynamic dysfunction in youth with T1D.