title: Recurrent Primary Focal Segmental Glomerulosclerosis Managed With Intensified Plasma Exchange and Concomitant Monitoring of Soluble Urokinase-Type Plasminogen Activator Receptor-Mediated Podocyte β3-integrin Activation.
abstract: BACKGROUND
  Primary focal segmental glomerulosclerosis (FSGS) often causes nephrotic proteinuria and frequently results in end-stage renal disease and recurrence after kidney transplantation. Recent studies describe soluble urokinase-type plasminogen activator receptor (suPAR) as a circulating factor implicated in FSGS.
  
  
  METHODS
  This single-center study included 12 adult patients with histologically proven primary FSGS (n = 2) or recurrent FSGS after transplantation (n = 10). The effect of plasma exchange (PE) on clinical outcome, suPAR levels, and in vitro podocyte β3-integrin activation was investigated over a median of 11 (6-18) sessions of PE.
  
  
  RESULTS
  The course of treatment was monitored in a total of 70 sessions of PE, which partly eliminated suPAR, with a mean reduction of 37 ± 12% of serum concentration per session. However, a substantial rebound was observed between sessions, with suPAR levels reaching 99 ± 22% of the pretreatment levels after a median of 4 days. Podocyte β3-integrin activation dropped significantly after PE but rebounded within 4 days concomitant with a rising suPAR level. In 11 of 12 patients, multimodal treatment (including extensive PE) reduced proteinuria significantly (from 5.3 [2.0-7.8] to 1.0 [0.4-1.6] g/d), indicating clinical efficacy of the therapy. One patient suffered allograft loss due to FSGS recurrence. A persisting response was independent of a lasting reduction in the level of total suPAR because there was no sustained significant change in suPAR levels before and after the course of intensified treatment (3814 ± 908 to 3595 ± 521 pg/mL; P = 0.496).
  
  
  CONCLUSIONS
  We conclude that multimodal therapy including extensive PE was associated with stabilization of recurrent FSGS and a temporary lowering of plasma suPAR as well as podocyte β3-integrin activation. Whether a sustained lowering of total suPAR results in further improved outcomes requires additional study.
authors.affiliation: 1 Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany. 2 Department of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany. 3 Department of Medicine, Rush University Medical Center, Chicago, IL.
authors.forename: Oliver
authors.initials: O
authors.lastname: Staeck
authors.forename: Torsten
authors.initials: T
authors.lastname: Slowinski
authors.forename: Ina
authors.initials: I
authors.lastname: Lieker
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Wu
authors.forename: Birgit
authors.initials: B
authors.lastname: Rudolph
authors.forename: Danilo
authors.initials: D
authors.lastname: Schmidt
authors.forename: Susanne
authors.initials: S
authors.lastname: Brakemeier
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Changli
authors.initials: C
authors.lastname: Wei
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Fabian
authors.initials: F
authors.lastname: Halleck
authors.forename: Dmytro
authors.initials: D
authors.lastname: Khadzhynov
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D010951:Plasma Exchange / Q000379:methods*; D050199:Podocytes / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D039661:Integrin beta3; D055293:Receptors, Urokinase Plasminogen Activator