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.Focal segmental glomerulosclerosis (FSGS) represents up to 20 percent of glomerular disease and is a leading cause of end-stage renal failure 1 . It affects native kidneys as well as renal allografts and the rate of recurrence of disease after transplantation is close to 30% in FSGS patients 2 .The pathophysiology and etiology of FSGS is still unclear 3 . However, it has been speculated that certain circulating factors might contribute to the initiation of renal injury 4 as evidenced by recurrence of FSGS after kidney transplantation 5 and the induction of remission after plasma exchange in subjects with recurrent FSGS early post renal transplantation 6 . Further evidence of potential circulating factors is the induction of proteinuria in kidneys of rats by administration of serum from FSGS patients 7 and the transmission of FSGS from mother to child 8 . In addition, it was reported that re-transplantation of a renal allograft with rapidly recurrent FSGS in a recipient with primary FSGS as underlying disease into a second recipient without native FSGS resulted in complete remission 9,10 .Several proteins have been suggested as the causative circulating factors responsible for the occurrence of primary FSGS or recurrence of disease after kidney transplantation, including cardiotrophin-like cytokine-1

Prognostic Role of Soluble Urokinase Plasminogen Activator Receptor at the Emergency Department: A Position Paper by the Hellenic Sepsis Study Group

“…This interaction is further enhanced among African Americans who carry the highrisk APOL1 genotype [8]. This effect on the glomeruli leading to proteinuria is consistent with the recently reported greater values of suPAR among patients with focal segmental glomerulosclerosis [9].…”

Elevated suPAR Is an Independent Risk Marker for Incident Kidney Disease in Acute Medical Patients

“…Differences in the assays used to measure suPAR may also contribute to variations in suPAR values. A recent study comparing the assay used by our hospital (suPARnostic R AUTO Flex ELISA) to another common assay (Quantikine R Human uPAR-Immunoassay) found that suPARnostic R yielded significantly lower suPAR in healthy controls and higher suPAR in patients with kidney disease (Winnicki et al, 2019).…”

Autoimmunity in Focal Segmental Glomerulosclerosis: A Long-Standing Yet Elusive Association

“…Since suPAR can be cleaved into several shorter molecules, some authors suggested that a hypoglycosylated fragment not readily detected by standard assays, rather than full-length suPAR, could be responsible for FSGS pathogenesis (52). In a recent study, a novel method able to identify both full-length and suPAR fragments outperformed the conventional ELISA assay in discriminating FSGS cases from other proteinuric nephropathies in a single-center cohort (53), but external validation has not been reported yet.…”