title: Potential role of soluble ST2 protein in idiopathic nephrotic syndrome recurrence following kidney transplantation.
abstract: BACKGROUND
  Corticosteroid-resistant idiopathic nephrotic syndrome (INS) recurs rapidly after transplantation in 30% to 50% of transplant recipients, suggesting the presence of 1 or more circulating factors that alter the glomerular filtration barrier. We investigated the possible role in INS recurrence of soluble ST2 (sST2) protein, a marker of T helper type 2 (T(H)2) cells and a factor predicted to be regulated by the transcription factor c-Maf; involvement of sST2 protein would be consistent with the observation that both T(H)2 cells and c-Maf appear to be activated during INS relapse.
  
  
  METHODS
  Retrospective observational study.
  
  
  METHODS
  Patients with biopsy-proven corticosteroid-resistant INS who had undergone kidney transplantation between September 1983 and April 2007 (n = 71). A control group consisting of proteinuric transplant recipients with kidney failure unrelated to INS (n = 34).
  
  
  METHODS
  Patients who developed INS recurrence after transplantation (n = 31) were compared with those in whom INS did not recur (n = 40) and the control group. Recurrence of INS was defined as urine protein excretion greater than 2 g/d immediately after transplantation that persisted at greater than 1 g/d despite treatment or a kidney graft biopsy showing minimal change glomerulonephritis or focal segmental glomerulosclerosis.
  
  
  METHODS
  Urine protein excretion in the 3 groups was 5.0 g/d (range, 1.3 to 10.5), 0.14 g/d (range, 0 to 0.46), and 4.3 g/d (range, 3 to 6.2). The sST2 protein was analyzed both quantitatively and qualitatively in patient sera, and its activity was tested in vitro on a mouse podocyte cell line and in vivo in rats.
  
  
  RESULTS
  sST2 protein levels were significantly increased after transplantation in patients with INS recurrence compared with the 2 other groups (617.5 versus 23 pg/mL; P < 0.001 and 158.5 pg/mL; P < 0.01 respectively). However, patients with recurrence expressed a normal sST2 isoform, and the sST2 protein was unable to induce podocyte injury in vitro or trigger proteinuria in rats.
  
  
  CONCLUSIONS
  Pretransplantation and posttransplantation sera do not always represent paired samples.
  
  
  CONCLUSIONS
  These data suggest that sST2 protein is a marker of INS recurrence that does not seem to be involved in the development of INS.
authors.affiliation: INSERM U643, CHU Nantes, Institut de Transplantation et de Recherche en Transplantation (ITERT) Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bruneau
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Le Berre
authors.forename: Caroline
authors.initials: C
authors.lastname: Hervé
authors.forename: Asta
authors.initials: A
authors.lastname: Valanciuté
authors.forename: Maud
authors.initials: M
authors.lastname: Kamal
authors.forename: Jeanne
authors.initials: J
authors.lastname: Naulet
authors.forename: Laurent
authors.initials: L
authors.lastname: Tesson
authors.forename: Yohann
authors.initials: Y
authors.lastname: Foucher
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: Djillali
authors.initials: D
authors.lastname: Sahali
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D019556:COS Cells; D002461:Cell Line, Transformed; D002648:Child; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000097:blood / Q000502:physiology*; D012189:Retrospective Studies; D055502:Secondary Prevention; D055815:Young Adult
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface