MO405: Leucine-Rich Alpha-2-Glycoprotein as a Potential Marker of Mesangial Cell Proliferation in Immunoglobulin a Nephropathy

Abstract

BACKGROUND AND AIMS Leucine-rich alpha-2-glycoprotein (LRG1) is a novel proangiogenic factor involved in the abnormal angiogenesis and renal fibrosis in diabetic nephropathy by potentiating endothelial transforming growth factor-beta/activin receptor-like kinase 1 (TGF-β/ALK1) signalling [1]. TGF-β mediates mesangial matrix accumulation culminating in the development of glomerulosclerosis [2], which also occurs in immunoglobulin A nephropathy (IgAN) patients. Our study aims to evaluate LRG1 as a marker of mesangial cell proliferation in IgAN patients. METHODS: Adults with a morphologically confirmed IgAN by the presence of IgA deposits by immunofluorescence microscopy were included in the study. Diabetes mellitus, oncology, acute inflammation processes were exclusion criteria. Serum LRG1 was detected using ELISA. RESULTS A total of 73 patients with IgAN were included [mean age 41 years, interquartile range (IQR) 35–47; range, 21–65; 65.8% men]. The median estimated glomerular filtration rate (eGFR) was 44 (IQR 24–83, range 4–133) mL/min/1.73m2. Kidney biopsies were analyzed according to the Oxford classification: M0 in 10 (13,7%), M1 in 56 (76.7%) patients. The median serum LRG1 was 49 µg/mL (IQR 40.7–57.7, range 29–133.3). Bivariate analyses showed that plasma LRG1 was negatively associated with eGFR (rho = −0.342, P = 0.003). A linear model showed that GFR decline for 1 mL/min was associated with an increase of LRG1 for 0.194 µg/mL. In IgAN patients with an M1-score LRG1 was higher (P = 0027, Mann–Whitney U test), the area under the ROC curve value for serum LRG1 was 0.739. CONCLUSION Serum LRG1 increases with GFR decline in patients with IgAN and at the same time correlates with mesangial hypercellularity according to Oxford classification. Therefore, LRG1 might be a potential marker of advanced disease in IgAN.