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

发现并初步验证 α 1-B 糖蛋白碎片作为儿童类固醇耐药性肾病综合征的鉴别尿液生物标志物

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作者:Nuntawan Piyaphanee, Qing Ma, Oran Kremen, Kimberly Czech, Kenneth Greis, Mark Mitsnefes, Prasad Devarajan, Michael R Bennett

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 α 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.

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