title: Circulating suPAR in two cohorts of primary FSGS.
abstract: Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to primary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease. Here, we analyzed circulating suPAR levels in two cohorts of children and adults with biopsy-proven primary FSGS: 70 patients from the North America-based FSGS clinical trial (CT) and 94 patients from PodoNet, the Europe-based consortium studying steroid-resistant nephrotic syndrome. Circulating suPAR levels were elevated in 84.3% and 55.3% of patients with FSGS patients in the CT and PodoNet cohorts, respectively, compared with 6% of controls (P<0.0001); inflammation did not account for this difference. Multiple regression analysis suggested that lower suPAR levels associated with higher estimated GFR, male sex, and treatment with mycophenolate mofetil. In the CT cohort, there was a positive association between the relative reduction of suPAR after 26 weeks of treatment and reduction of proteinuria, with higher odds for complete remission (P=0.04). In the PodoNet cohort, patients with an NPHS2 mutation had higher suPAR levels than those without a mutation. In conclusion, suPAR levels are elevated in geographically and ethnically diverse patients with FSGS and do not reflect a nonspecific proinflammatory milieu. The associations between a change in circulating suPAR with different therapeutic regimens and with remission support the role of suPAR in the pathogenesis of FSGS.
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Changli
authors.initials: C
authors.lastname: Wei
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Dong
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Friedman
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Gassman
authors.forename: June L
authors.initials: JL
authors.lastname: McMahan
authors.forename: Milena
authors.initials: M
authors.lastname: Radeva
authors.forename: Karsten M
authors.initials: KM
authors.lastname: Heil
authors.forename: Agnes
authors.initials: A
authors.lastname: Trautmann
authors.forename: Ali
authors.initials: A
authors.lastname: Anarat
authors.forename: Sevinc
authors.initials: S
authors.lastname: Emre
authors.forename: Gian M
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.forename: Dieter
authors.initials: D
authors.lastname: Haffner
authors.forename: Debbie S
authors.initials: DS
authors.lastname: Gipson
authors.forename: Frederick
authors.initials: F
authors.lastname: Kaskel
authors.forename: Dagmar-Christiane
authors.initials: DC
authors.lastname: Fischer
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
mesh_terms: D000293:Adolescent; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D055293:Receptors, Urokinase Plasminogen Activator; D002097:C-Reactive Protein; D009173:Mycophenolic Acid