title: Podocyte effacement closely links to suPAR levels at time of posttransplantation focal segmental glomerulosclerosis occurrence and improves with therapy.
abstract: BACKGROUND
  Focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation in more than 30% of cases and can lead to allograft loss. Serum soluble urokinase-type plasminogen activator receptor (suPAR) is implicated in the pathogenesis of native and recurrent FSGS.
  
  
  METHODS
  We conducted a retrospective study of 25 adults with posttransplantation FSGS. We investigated the relationship between suPAR levels and podocyte changes and the impact of therapy on podocyte structure. We assessed response to therapy by improvement in proteinuria, allograft function, and resolution of histologic changes.
  
  
  RESULTS
  A median (interquartile range) of 15 (10-23) plasmapheresis sessions was administered; 13 of the subjects also received rituximab. Median pretreatment suPAR levels were higher among those with severe (≥75%) versus those with mild (≤25%) podocyte foot process effacement (13,030 vs. 4806 pg/mL; P=0.02). Overall, mean±SD of proteinuria improved from 5.1±3.8 to 2.1±2.8 mg/dL (P=0.003), mean podocyte effacement decreased from 57%±33% to 22%±22% (P=0.0001), estimated glomerular filtration rates increased from median (interquartile range) of 32.9 (20.6-44.2) to 39.3 (28.8-63.4; P<0.0001), and suPAR levels decreased from a median of 6.781 to 4.129 pg/mL (P=0.02) with therapy.
  
  
  CONCLUSIONS
  Podocyte effacement is the first pathologic manifestation of FSGS after transplantation. The degree of podocyte effacement correlates with suPAR levels at time of diagnosis. Response to therapy results in significant reduction of suPAR levels and complete or significant improvement of podocyte effacement.
authors.affiliation: 1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 2 Department of Medicine, Rush University Medical Center, Chicago, IL. 3 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. 4 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL. 5 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL. 6 Department of Medicine, Union Memorial Hospital, Baltimore, MD. 7 Address correspondence to: Nada Alachkar, M.D., Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 971, Baltimore, MD 21205 and Jochen Reiser, M.D., Ph.D., Department of Medicine, Rush University Medical Center, Cohn Research Building, Suite 724, 1735 W. Harrison Street, Chicago, IL 60612.
authors.forename: Nada
authors.initials: N
authors.lastname: Alachkar
authors.forename: Changli
authors.initials: C
authors.lastname: Wei
authors.forename: Lois J
authors.initials: LJ
authors.lastname: Arend
authors.forename: Annette M
authors.initials: AM
authors.lastname: Jackson
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Racusen
authors.forename: Alessia
authors.initials: A
authors.lastname: Fornoni
authors.forename: George
authors.initials: G
authors.lastname: Burke
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
authors.forename: Kavita
authors.initials: K
authors.lastname: Kakkad
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Estrella
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D050199:Podocytes / Q000187:drug effects / Q000473:pathology*; D011507:Proteinuria / Q000097:blood / Q000473:pathology / Q000628:therapy; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012008:Recurrence; D012189:Retrospective Studies; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D007166:Immunosuppressive Agents; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D000069283:Rituximab; D002097:C-Reactive Protein