Relationship between Serum Soluble Urokinase Plasminogen Activator Receptor Level and Steroid Responsiveness in FSGS

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 patients with 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 associated with steroid response in patients with FSGS (odds ratio, 85.02; P=0.001). Patients who were 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 patients with FSGS, which differs from the finding in patients with MCD and MN. A suPAR assay may help predict steroid response in patients with primary FSGS.