title: Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis.
abstract: OBJECTIVE
  To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy.
  
  
  METHODS
  mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year.
  
  
  RESULTS
  mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices.
  
  
  CONCLUSIONS
  Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.
authors.affiliation: Department of Medicine, Division of Rheumatology, New York University School of Medicine, NY, USA. izmirp01@nyumc.org
authors.forename: Peter M
authors.initials: PM
authors.lastname: Izmirly
authors.forename: Laura
authors.initials: L
authors.lastname: Barisoni
authors.forename: Jill P
authors.initials: JP
authors.lastname: Buyon
authors.forename: Mimi Y
authors.initials: MY
authors.lastname: Kim
authors.forename: Tania L
authors.initials: TL
authors.lastname: Rivera
authors.forename: Julie S
authors.initials: JS
authors.lastname: Schwartzman
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Weisstuch
authors.forename: David T
authors.initials: DT
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Bernstein
authors.forename: Chung-E
authors.initials: CE
authors.lastname: Tseng
authors.forename: Howard M
authors.initials: HM
authors.lastname: Belmont
authors.forename: Charles T
authors.initials: CT
authors.lastname: Esmon
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: Anca D
authors.initials: AD
authors.lastname: Askanase
authors.forename: David B
authors.initials: DB
authors.lastname: Thomas
authors.forename: Robert M
authors.initials: RM
authors.lastname: Clancy
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007672:Kidney Cortex / Q000098:blood supply* / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface