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. 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 P 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.