Abstract
Objective The soluble urokinase plasminogen activator receptor (suPAR) is associated with kidney diseases and is used as a prognostic factor of renal function progression. The aim of this study was to explore whether circulating suPAR was associated with antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) disease activity. Methods We evaluated 90 AAV patients with follow-up data and 35 normal controls; their plasma suPAR and C-reactive protein (CRP) levels were measured by ELISA. Associations between these levels, clinical parameters, and prognosis were analyzed. Results Plasma suPAR levels in AAV patients were significantly higher than in healthy controls (5,920.08 ± 3,447.17 vs. 1,441.97 ± 835.04 pg/mL, P < 0.001). Furthermore, suPAR was significantly elevated in AAV patients in active stage compared to those in partial remissions (6,492.19 ± 3,689.48 vs. 5,031.86 ± 2,489.01 pg/mL, P = 0.039). Correlation analyses demonstrated that suPAR levels positively correlated with initial serum creatinine, BVAS, CRP, and procalcitonin concentration, and negatively correlated with eGFR and C3 circulating levels. In a Kaplan-Meier survival analysis, patients with plasma suPAR levels >5683.3 pg/mL showed poorer survival than patients with lower levels (log-rank, P = 0.001). Besides, multivariate analyses confirmed that plasma suPAR levels were an independent adverse prognostic factor for a composite outcome of end-stage renal disease (ESRD) or death, after adjusting for age and gender (HR 1.05, 95% CI = 1.01 − 1.11, P = 0.043). Receiver operating characteristic curves showed a suPAR cutoff value >6662.2 pg/mL for composite outcome with 68% sensitivity and 88% specificity, with an AUC = 0.82, (95% CI = 0.68 − 0.96, P < 0.001). Conclusion Circulating suPAR levels might be a marker of activity correlated with disease activity in AAV patients, and, to some extent, could be a factor of poor prognosis.
Highlights
Antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) is a kind of autoimmune disease characterized by pauci-immune necrotizing inflammation of the small blood vessels, with an annual incidence of 13-20/million inhabitants [1]
Several studies have demonstrated the role of Soluble urokinase plasminogen activator receptor (suPAR) as a potential biomarker in various types of cancer, cardiovascular disease, liver fibrosis, renal disorders, and systemic lupus erythematosus, as well as in rheumatic diseases where elevated suPAR levels have been related to poor prognosis [7,8,9,10,11]
Prior reports had shown that there were remarkably higher suPAR levels in 13 patients with MPO-ANCA-associated glomerulonephritis compared with healthy controls [24], as well as significantly higher suPAR levels in 5 ANCAassociated glomerulonephritis (ANCA-GN) patients than in non-ANCA-GN patients [32]
Summary
Antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) is a kind of autoimmune disease characterized by pauci-immune necrotizing inflammation of the small blood vessels, with an annual incidence of 13-20/million inhabitants [1]. Kidneys are the most susceptible organs; the disease is frequently manifested as a pauci-immune focal segmental necrotizing glomerulonephritis with a very rapid decline in renal function [4]. Mediators of Inflammation receptor (uPAR), which is part of the plasminogen activation system and implicated in pathological processes of inflammation, proteolysis, tissue remodeling, and cancer metastasis [5, 6]. It has been shown that uPAR is overexpressed in inflammatory cells after activation by cytokines, whereas plasma suPAR levels further increase under inflammatory or infectious conditions [16,17,18]
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