Potential role of soluble ST2 protein in idiopathic nephrotic syndrome recurrence following kidney transplantation.
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.
Bruneau
Sarah
S
INSERM U643, CHU Nantes, Institut de Transplantation et de Recherche en Transplantation (ITERT) Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.
Le Berre
Ludmilla
L
Hervé
Caroline
C
Valanciuté
Asta
A
Kamal
Maud
M
Naulet
Jeanne
J
Tesson
Laurent
L
Foucher
Yohann
Y
Soulillou
Jean-Paul
JP
Sahali
Djillali
D
Dantal
Jacques
J
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
D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface