title: A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.
abstract: It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS.
authors.affiliation: Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Joann M
authors.initials: JM
authors.lastname: Spinale
authors.affiliation: 1] Arbor Research for Collaborative for Health, Ann Arbor, Michigan, USA [2] Division of Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Mariani
authors.affiliation: Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Shiv
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jidong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Arbor Research for Collaborative for Health, Ann Arbor, Michigan, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Weyant
authors.affiliation: Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Song
authors.affiliation: Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Hetty N
authors.initials: HN
authors.lastname: Wong
authors.affiliation: Division of Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Troost
authors.affiliation: Nephrology Division, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Gadegbeku
authors.affiliation: Division of Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Debbie S
authors.initials: DS
authors.lastname: Gipson
authors.affiliation: Division of Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.affiliation: Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Nihalani
authors.affiliation: Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Holzman
mesh_terms: D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D003404:Creatinine / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000097:blood* / Q000473:pathology / Q000652:urine*; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000473:pathology / Q000652:urine; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000473:pathology / Q000652:urine; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000473:pathology / Q000652:urine; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000097:blood / Q000473:pathology / Q000652:urine; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D003404:Creatinine