title: Serum suPAR in patients with FSGS: trash or treasure?
abstract: The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both overexpression of uPAR on podocytes and the administration of suPAR cause proteinuria in mice. The common pathogenic mechanism involves the activation of podocyte β3-integrin. Increased activation of β3-integrin is also observed in patients with focal and segmental glomerulosclerosis (FSGS). These observations form the basis for the hypothesis that suPAR may be the circulating factor causing FSGS. A recent study fosters this idea by demonstrating increased suPAR levels in the serum of patients with FSGS and reporting an association with recurrence after transplantation and response to plasmapheresis. However, this study was heavily biased, and subsequent studies have given conflicting results. Although the experimental work is very suggestive, at present there is no proof that any known human suPAR fragment causes FSGS in humans. We therefore suggest that the measurement of suPAR using currently available assays has absolutely no value at the present time in decision-making in routine clinical practice.
authors.affiliation: Department of Nephrology 464, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. r.maas@aig.umcn.nl
authors.forename: Rutger J H
authors.initials: RJ
authors.lastname: Maas
authors.forename: Jeroen K J
authors.initials: JK
authors.lastname: Deegens
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003661:Decision Support Techniques; D004195:Disease Models, Animal; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*
chemical_list: D015415:Biomarkers; C061248:ITGB3 protein, human; D039661:Integrin beta3; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator