Blood TGF-β1 and miRNA-21-5p levels predict renal fibrosis and outcome in IgA nephropathy.

Abstract

IgA nephropathy(IgAN), the most common primary glomerulonephritis, often presents as advanced renal failure with end-stage renal disease at diagnosis. Tubulointerstitial injury and fibrosis on histology are the most important predictors of renal outcome. A non-invasive biomarker is required for assessment of progression in IgA nephropathy. We investigated the utility of blood profibrotic molecules, TGF-β1 and miRNA-21-5p(miR-21), to identify a non-invasive biomarker for renal fibrosis in IgAN. The study included 30 IgAN (mean age 31.5 ± 9years) at the time of initial diagnosis, 25 age-sex-matched healthy controls and 10 Lupus nephritis patients as disease controls. Serum TGF-β1 was analyzed by enzyme-linked immunosorbent assay and plasma miR-21 by qRT-PCR, normalized with U6-snRNA. The levels were correlated with clinical features, laboratory parameters, histological Oxford MEST-C score and renal outcome. The serum TGF-β1 and plasma miR-21 were significantly higher in patients with IgAN than in healthy controls. TGF-β1 significantly correlated with serum creatinine, eGFR, Oxford T score and miR-21. High plasma miR-21 was significantly associated with T score and interstitial inflammation. On multivariate analysis, high levels of TGF-β1 and miR-21 correlated with lower eGFR and T score, respectively. On a follow-up period of 21.5months, high miR-21 expression at diagnosis was associated (p = 0.02) with a poor renal outcome havinga shorter time to doubling of serum creatinine. High blood TGF-β1 and miR-21 expression at diagnosis of IgAN show significant correlation with renal function and degree of chronic tubulointerstitial injury on histology.