Urinary EPCR and dermcidin as potential novel biomarkers for severe adult OSA patients.

BACKGROUND: Due to low predictive values of obstructive sleep apnea (OSA) screening tools, there is a need for biomarker for screening of OSA patients at an early stage. The aim of the study was to evaluate differentially expressed proteins in blood and urine samples of OSA patients. METHODS: In this study, we used isobaric tagging for relative and absolute quantification (iTRAQ) based proteomics approach to identify differentially expressed proteins, which were subsequently verified and validated using enzyme-linked immunosorbent assay (ELISA) technique in adult OSA patients. RESULTS: Seventeen differentially expressed proteins were selected from iTRAQ data for verification, based on their clinical significance and reproducibility among different iTRAQ experiment sets. Five of these proteins (plasma = 2; urine = 3) were further validated in plasma (non-OSA- = 42; OSA = 198) and urine samples (non-OSA = 46; OSA = 197). ROC curve analysis for all OSA vs. non-OSA subjects ensured optimal diagnostic utility of two urinary proteins: Endothelial protein c receptor (EPCR) (AUC = 73%, cut-off: 35 pg/ml) and dermcidin (AUC = 74%, cut-off: 4.6 pg/ml). For severe OSA, diagnostic accuracy significantly improved with AUC as 88% and 82% for EPCR (cut-off: 46 pg/ml) and dermcidin (cut-off: 5.2 pg/ml) respectively. Sensitivity and specificity of combined performance of both urinary proteins for severe OSA were 94% and 91% respectively. CONCLUSION: In this study, urinary EPCR and dermcidin emerged as novel biomarkers for screening severe OSA patients.

Contribution of renal and non-renal clearance on increased total clearance of adalimumab in glomerular disease.

The contribution of renal and non-renal clearance toward targeted concentrations and/or effects of therapeutic proteins in nephrotic patients are unknown. This study dissected the contribution of clearance pathways to adalimumab elimination in patients with focal segmental glomerulosclerosis (FSGS). Urine was collected from seven patients treated with adalimumab. Renal clearance (ClR ) was measured and non-renal clearance (ClNR ) was calculated as the difference between total clearance and ClR . Differences in cumulative amount in urine, ClR, and ClNR between study weeks 1 and 16 and relationships between proteinuria (protein:creatinine ratio (Up/c)), and ClR and ClNR were evaluated. Up to 13% of the adalimumab dose was lost in urine. ClNR contributed more than ClR to enhanced total clearance. There was a nonlinear relationship between Up/c and ClR (R(2) 0.7059); an increase in ClR beginning at Up/c of 12 mg/mg [slope 1.755, (C.I. -7.825 to 11.34)]. There was a linear relationship between Up/c and ClNR (R(2) 0.5039); for every one unit increase in Up/c, ClNR would increase by 3.5 mL/hr (P = 0.01). Both ClR and ClNR contribute to enhanced total clearance of adalimumab in glomerular disease secondary to FSGS. Additional research is needed to identify mechanisms for the increased ClNR pathways.