Potential role of soluble ST2 protein in idiopathic nephrotic syndrome recurrence following kidney transplantation
S Bruneau, L Le Berre, C Hervé, A Valanciuté… - American journal of …, 2009 - Elsevier
American journal of kidney diseases, 2009•Elsevier
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
(TH2) 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 TH2 cells …
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
(TH2) 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 TH2 cells …
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 (TH2) 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 TH2 cells and c-Maf appear to be activated during INS relapse.
STUDY DESIGN
Retrospective observational study.
SETTING & PARTICIPANTS
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).
PREDICTOR
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.
OUTCOMES & MEASUREMENTS
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.
LIMITATIONS
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.
Elsevier
