Elevated serum soluble α3(IV)NC1 correlates with kidney injury and worse outcome in patients with anti-glomerular basement membrane disease

Background Anti-glomerular basement membrane (GBM) disease is the most severe form of autoimmune kidney diseases characterized by pathogenic autoantibodies against GBM component, α3(IV)NC1. However, the status of circulating soluble α3(IV)NC1 (also known as tumstatin) in patients with anti-GBM disease and its clinical relevance remain unclear. The aim of this study was to investigate the serum soluble α3(IV)NC1 level [ss-α3(IV)NC1] in patients with anti-GBM disease, and to analyze its association to clinical characteristics. Methods Seventy patients with anti-GBM disease and 30 healthy individuals were enrolled. Ss-α3(IV)NC1 was measured by enzyme-linked immunosorbent assay. The level was compared and analyzed with clinical-pathological features and kidney outcome, and the statistical significance was determined. Results Ss-α3(IV)NC1 concentrations were elevated in 41 (58.6%) patients with anti-GBM disease and 0 (0.0%) healthy individuals. They were significantly higher in patients with anti-GBM disease (18.32 ± 9.56 ng/mL) than those in healthy individuals (5.84 ± 2.78 ng/mL) ( P < 0.001). Ss-α3(IV)NC1 correlated with age ( r = 0.385, P = 0.001), serum creatinine ( r = 0.286, P = 0.016), eGFR ( r = -0.304, P = 0.010), crescent percentage ( r = 0.339, P = 0.030), and normal glomeruli percentage ( r = -0.354, P = 0.023). Kaplan–Meier analysis revealed that patients with elevated ss-α3(IV)NC1 had a worse kidney outcome than those with normal level ( P = 0.011). Conclusions The ss-α3(IV)NC1 was abnormally elevated in patients with anti-GBM disease. Elevated ss-α3(IV)NC1 was associated with the disease severity in anti-GBM disease. The role of these elevated levels warrants further investigation.