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. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information .