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Biomark Insights. 2016 Jan 13;11:1-6. doi: 10.4137/BMI.S31633. eCollection 2016.

Urinary Vitamin D-Binding Protein as a Biomarker of Steroid-Resistant Nephrotic Syndrome.

Biomarker insights

Michael R Bennett, Angad Pordal, Christopher Haffner, LaTawnya Pleasant, Qing Ma, Prasad Devarajan

Affiliations

  1. Assistant Professor, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  2. Summer Student, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  3. Research Assistant, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  4. Clinical Fellow, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  5. Professor, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

PMID: 26792978 PMCID: PMC4712977 DOI: 10.4137/BMI.S31633

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 m(2). 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.

Keywords: biomarkers; focal segmental glomerulosclerosis; minimal change disease; nephrotic syndrome; steroid resistance; vitamin D

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