The Plasma Soluble Urokinase Plasminogen Activator Receptor Is Related to Disease Activity of Patients with ANCA-Associated Vasculitis
Fei Huang, Yueqiang Li, Ranran Xu, Anying Cheng, Yongman Lv, Qingquan Liu
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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mn>5,920.08</mml:mn><mml:mo>±</mml:mo><mml:mn>3,447.17</mml:mn></mml:math> vs. <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mn>1,441.97</mml:mn><mml:mo>±</mml:mo><mml:mn>835.04</mml:mn><mml:mtext> </mml:mtext><mml:mtext>pg</mml:mtext><mml:mo>/</mml:mo><mml:mtext>mL</mml:mtext></mml:math>, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:math>). Furthermore, suPAR was significantly elevated in AAV patients in active stage compared to those in partial remissions (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mn>6,492.19</mml:mn><mml:mo>±</mml:mo><mml:mn>3,689.48</mml:mn></mml:math> vs. <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mn>5,031.86</mml:mn><mml:mo>±</mml:mo><mml:mn>2,489.01</mml:mn><mml:mtext> </mml:mtext><mml:mtext>pg</mml:mtext><mml:mo>/</mml:mo><mml:mtext>mL</mml:mtext></mml:math>, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.039</mml:mn></mml:math>). 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, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.001</mml:mn></mml:math>). 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% <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mtext>CI</mml:mtext><mml:mo>=</mml:mo><mml:mn>1.01</mml:mn><mml:mo>−</mml:mo><mml:mn>1.11</mml:mn></mml:math>, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.043</mml:mn></mml:math>). Receiver operating characteristic curves showed a suPAR cutoff value >6662.2 pg/mL for composite outcome with 68% sensitivity and 88% specificity, with an <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"><mml:mtext>AUC</mml:mtext><mml:mo>=</mml:mo><mml:mn>0.82</mml:mn></mml:math>, (95% <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M11"><mml:mtext>CI</mml:mtext><mml:mo>=</mml:mo><mml:mn>0.68</mml:mn><mml:mo>−</mml:mo><mml:mn>0.96</mml:mn></mml:math>, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M12"><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:math>). 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.