title: The soluble urokinase receptor is not a clinical marker for focal segmental glomerulosclerosis.
abstract: The soluble urokinase receptor (suPAR) promotes proteinuria and induces focal segmental glomerulosclerosis (FSGS)-like lesions in mice. A serum suPAR concentration cutoff of 3000 pg/ml has been proposed as a clinical biomarker for patients with FSGS. Interestingly, several studies in patients with glomerulopathy found an inverse correlation between the estimated glomerular filtration rate (eGFR) and suPAR. As patients with FSGS present at different eGFRs, we studied the relationship between eGFR and suPAR in a cohort of 476 non-FSGS patients and 54 patients with biopsy-proven idiopathic FSGS. In the non-FSGS patients, eGFR was the strongest significant determinant of suPAR. The proposed cutoff for suPAR in FSGS patients was exceeded in 17%, 39%, and 88% in patients with eGFRs of more than 60, 45-60, and 30-45 ml/min per 1.73 m(2), respectively. In patients with eGFR of <30 ml/min per 1.73 m(2), suPAR exceeded the cutoff in 95% of patients. Levels of suPAR in patients with idiopathic FSGS overlapped with non-FSGS controls and for any given eGFR did not discriminate FSGS cases from non-FSGS controls. In the overall cohort, there was a negative association between idiopathic FSGS and suPAR, and idiopathic FSGS was not an independent predictor of FSGS concentration over 3000 pg/ml. Thus, this study does not support an absolute, eGFR-independent, suPAR concentration cutoff as a biomarker for underlying FSGS pathology and questions the validity of relative, eGFR-dependent suPAR cutoff values.
authors.affiliation: 1] Department of Nephrology, UZ Leuven, Leuven, Belgium [2] Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Björn
authors.initials: B
authors.lastname: Meijers
authors.affiliation: Department of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Rutger J H
authors.initials: RJ
authors.lastname: Maas
authors.affiliation: 1] Department of Nephrology, UZ Leuven, Leuven, Belgium [2] Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Sprangers
authors.affiliation: 1] Department of Nephrology, UZ Leuven, Leuven, Belgium [2] Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Ruben
authors.initials: R
authors.lastname: Poesen
authors.affiliation: 1] Department of Nephrology, UZ Leuven, Leuven, Belgium [2] Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Bammens
authors.affiliation: 1] Department of Nephrology, UZ Leuven, Leuven, Belgium [2] Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Naesens
authors.affiliation: Department of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Jeroen K J
authors.initials: JK
authors.lastname: Deegens
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dietrich
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Storr
authors.affiliation: Department of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.affiliation: 1] Department of Nephrology, UZ Leuven, Leuven, Belgium [2] Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.affiliation: 1] Department of Nephrology, UZ Leuven, Leuven, Belgium [2] Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D005260:Female; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood / Q000502:physiology*
chemical_list: D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator