Diagnostic and Prognostic Value of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) in Focal Segmental Glomerulosclerosis and Impact of Detection Method

Abstract

The plasma soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker for focal segmental glomerulosclerosis (FSGS), but its value is under discussion because of ambiguous results arising from different ELISA methods in previous studies. The aim of this study was to compare diagnostic performance of two leading suPAR ELISA kits and examine four objectives in 146 subjects: (1) plasma suPAR levels according to glomerular disease (primary, secondary and recurrent FSGS after kidney transplantation, other glomerulonephritis) and in healthy controls; (2) suPAR levels based on glomerular filtration rate; (3) sensitivity and specificity of suPAR for FSGS diagnosis and determination of optimal cut-offs; (4) suPAR as prognostic tool. Patients with FSGS showed significant higher suPAR values than patients with other glomerulonephritis and healthy individuals. This applied to subjects with and without chronic kidney disease. Although both suPARnostic™ assay and Quantikine Human uPAR ELISA Kit exerted high sensitivity and specificity for FSGS diagnosis, their cut-off values of 4.644 ng/mL and 2.789 ng/mL were significantly different. Higher suPAR was furthermore predictive for progression to end-stage renal disease. In summary, suPAR values must be interpreted in the context of population and test methods used. Knowing test specific cut-offs makes suPAR a valuable biomarker for FSGS.

Figure 1

Plasma suPAR levels in patients with FSGS total, primary FSGS, secondary FSGS, recurrence of FSGS after renal transplantation, other glomerulonephritis and healthy controls. (a) Results from suPARnostic™ assay: plasma suPAR levels of patients with FSGS (FSGS total, 6.58 ± 2.25 ng/mL) were significantly higher than in patients with other GN (3.28 ± 1.47 ng/mL) and healthy controls (1.53 ± 0.60 ng/mL). (b) Results from Quantikine Human uPAR ELISA Kit: suPAR levels in patients with FSGS (FSGS total, 3.54 ± 1.03 ng/mL) were significantly higher than in patients with other GN (3.07 ± 1.06 ng/mL) and healthy controls (2.07 ± 0.50 ng/mL). There was no significant difference in plasma suPAR levels between patients with primary FSGS, secondary FSGS and recurrence of FSGS after renal transplantation. P-values are based on the Mann-Whitney U test. Abbreviations: FSGS, focal segmental glomerulosclerosis; GN, glomerulonephritis; RTX, renal transplantation.

Figure 2

Receiver operating characteristic (ROC) analysis of the plasma soluble urokinase-type plasminogen activator receptor (suPAR) in patients FSGS vs. non-FSGS. (a) For the cut-off value of 4.644 ng/mL measured by the suPARnostic™ assay, sensitivity and specificity were both 0.91 with an AUC of 0.946 [95% CI 0.91 to 0.98]. (b) For the cut-off value of 2.789 ng/mL measured by the Quantikine Human uPAR ELISA Kit the sensitivity and specificity were 0.80 and 0.64, respectively with an AUC of 0.763 [95% CI 0.69 to 0.83].