Urinary mi-106a for the diagnosis of IgA nephropathy: Liquid biopsy for kidney disease

Abstract

BackgroundUrinary micro-RNA (miRNA) level may serve as non-invasive disease markers for immunoglobulin A nephropathy (IgAN), but urinary miRNA targets identified in previous studies may represent kidney scarring rather than being specific for IgAN. We aim to identify urinary miRNA targets for the diagnosis of IgAN by including hypertensive nephrosclerosis (HTN) as a control group. Methods In the development cohort, we performed complete miRNA profiling of urinary sediment in 33 patients with IgAN, 9 with HTN, and 9 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 72 IgAN, 34 HTN, and 20 healthy controls. Results In the development cohort, we identified 6 miRNA targets with urinary levels significantly increased in IgAN as compared to both HTN and CTL. In the validation study, all 6 miRNA targets remained increased than the other groups, although the result of miR-345 did not reach statistical significance. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-106a level for the diagnosis of IgAN was 0.742 (p < 0.0001), and the diagnostic performance was not further improved by having additional miRNA targets. At the cut-off ≥ 800 copy per 1000 copies of housekeeping gene, urinary miR-106a has 100% sensitivity and 14.8% specificity in detecting IgA nephropathy. Conclusions We identified 6 miRNA targets whose urinary levels are significantly elevated in IgAN, and urinary miR-106a level has an excellent sensitivity for the identification of IgAN. Further validation studies are needed to confirm its role in disease screening.