Relationship between serum soluble urokinase plasminogen activator receptor level and steroid responsiveness in FSGS

Abstract

Background and objectives Soluble urokinase plasminogen activator receptor (suPAR)was initially proposed as a pathogenic and predictive biomarker of primary FSGS, but the findings were controversial. This study aimed to clarify the clinical implications of suPAR. Design, setting, participants, &measurements The study enrolled 109 patientswith biopsy-proven primary FSGS who were administered prednisone between January 2011 and May 2013 and followed up for 6–24 months (median duration of follow-up, 12 months). Ninety-six healthy volunteers, 20 patients with minimal-change disease (MCD), and 22 patients with membranous nephropathy (MN) served as controls. Serum suPAR levels were measured using ELISA. Results suPAR levels in patients with FSGS (median, 3512 [interquartile range (IQR), 2232–4231] pg/ml) were significantly higher than in healthy controls (median, 1823 [IQR, 1563–2212] pg/ml; P,0.001), patients with MCD (median, 1678 [IQR, 1476–2182] pg/ml; P,0.001), and patients with MN (median, 1668 [IQR, 1327–2127] pg/ml; P,0.001). With 3000 pg/ml used as a threshold, suPAR levels were elevated in 48.6% of patients with FSGS, in contrast to 5% of patients with MCD and 4.5% of those with MN. suPAR levels were independently associatedwith steroid response in patientswith FSGS (odds ratio, 85.02; P=0.001). Patients whowere sensitive to steroids had significantly higher suPAR levels than nonsensitive patients (median, 3426 [IQR, 2670–5655] pg/ml versus 2523 [IQR, 1977–3460] pg/ml; P=0.001). A suPAR level of 3400 pg/ml was chosen as the optimal cutoff value for steroid response. At the 6-month follow-up in 84 patients with FSGS, suPAR levels were significantly decreased in those with suPAR level $3400 pg/ml (median, 4553 [IQR, 3771–6120] pg/ml versus 3149 [IQR, 2278–3953]; P=0.002) but were unchanged in patients with suPAR level,3400 pg/ml (median, 2359 [IQR, 2023– 2842] pg/ml versus 2490 [IQR, 1916–3623] pg/ml; P=0.09). Conclusions suPAR is specifically elevated in some patientswith FSGS,which differs fromthe finding in patients with MCD and MN. A suPAR assay may help predict steroid response in patients with primary FSGS.