Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome

Purpose: In this cross-sectional pilot study we set out to discover a non-invasive biomarker that could distinguish steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS). Experimental design: Urine and clinical data were collected from patients with idiopathic nephrotic syndrome and healthy controls. Using SELDI-TOF-MS, we identified an 11-fold upregulated 13.8 kDa fragment of alpha 1-B glycoprotein (A1BG) in urine in SRNS. To validate our findings, A1BG was detected by Western blot. Creatinine was measured and transformed to glomerular filtration rate (GFR) by the new Schwartz formula and classified to chronic kidney disease (CKD) stage. p-Values were determined by unpaired t-test and Mann-Whitney rank sum test. Microalbumin was also measured to determine albumin/creatinine ratios. Results: The 13.8 kDa A1BG was present in 7 of 19 patients with SRNS; but absent in all SSNS (n = 15) and controls (n = 10). The A1BG(+) patients had lower GFR than A1BG(-) patients (p<0.009) and tended to have higher CKD stage. Conclusion and clinical relevance: The 13.8 kDa A1BG fragment had a high discriminatory power for steroid resistance in pediatric nephrotic syndrome, but is only present in a subset of patients. Additional longitudinal studies are required to determine the usefulness of this biomarker as a non-invasive predictive marker of therapeutic response.