Urinary vitamin D-binding protein as a biomarker of steroid-resistant nephrotic syndrome

Abstract

Background: Idiopathic nephrotic syndrome (NS) is one of the most common glomerular disorders of childhood and is associated with increased urinary vitamin D-binding protein (uVDBP) excretion. We tested the hypothesis that uVDBP represents a biomarker to differentiate steroid-resistant nephrotic syndrome (SRNS) from the more benign forms of steroid-sensitive nephrotic syndrome (SSNS).Methods: This cross-sectional study included children with SRNS (n = 24), SSNS (n = 28), and normal controls (n = 5). Urine and clinical data were collected from patients. Measurements of uVDBP were performed with a commercially available ELISA kit and normalized to urine creatinine.Results: Concentrations of uVDBP were significantly higher (P , 0.001) in patients with SRNS (13,659 ng/mL, interquartile range [IQR] 477–22,979) than in patients with SSNS (94 ng/mL, IQR 53–202) and normal controls (23 ng/mL, IQR 22–99, P = 0.002). Significance did not change when the results were corrected for urine creatinine. uVDBP was significantly negatively correlated with estimated glomerular filtration rate (eGFR; R = −0.76, P = 0.03). However, uVDBP was still markedly elevated in patients with SRNS with eGFR .100 mL/minute/1.73 m2. There was a positive correlation between microalbuminuria (MALB/Cr) and uVDBP (R = 0.67, P , 0.001). However, uVDBP displayed a much higher discriminatory ability for distinguishing SRNS than MALB/Cr (area under the curve = 0.92 vs 0.67, respectively). An uVDBP cutoff of 362 ng/mL yielded the optimal sensitivity (80%) and specificity (83%) to distinguish SRNS from SSNS.Conclusions: In this preliminary study, uVDBP represents a noninvasive biomarker that could distinguish SRNS from the more benign SSNS with high discriminatory power.