Corticosteroids in recurrence of glomerular disease in renal transplantation: Do we know the right questions to ask?

For many decades, corticosteroids have been a mainstay of post-transplant therapy in pediatric solid organ transplantation, particularly in kidney transplantation. They have been shown to be very effective in preventing acute and late rejection episodes, and in the treatment and reversal of acute rejection episodes. However, chronic steroid use is fraught with numerous adverse effects, particularly in pediatric recipients (1). Patients often experience serious adverse effects as a result of chronic steroid use, including growth retardation, bone demineralization, hyperglycemia, hyperlipidemia, hypertension, cardiovascular disease, body disfigurement, weight gain, and cataracts (1). Not only do these adverse effects have significant impact on patients emotional and physical well-being, but treatment also increases rising healthcare costs (2). In addition to all of these problems, given the specific side effects patients may experience, the potential for medication non-adherence is great, especially in the adolescent population (3). In the past decade, there has been a shift toward dramatic steroid minimization in kidney transplant immunosuppression regimens. With the emergence of newer, effective immunosuppressive medications such as IL-2 blockers (daclizumab, basiliximab), T cell–depleting agents (alemtuzumab), anti-lymphocyte agents (thymoglobulin, rituximab), and new oral immunosuppressive agents, steroid minimization has become increasingly popular. Numerous strategies have been employed to either minimize or eliminate steroids from the immunosuppressive armamentarium. Measures such as alternate day steroids and late steroid withdrawal (>6 months post-transplant) have been utilized with varying degrees of success (4– 7). More recently, early rapid steroid discontinuation has been investigated in two randomized controlled trials (8, 9). Both implement the protocol in what are designated as ‘‘low risk’’ recipients. Each trial found growth improvement with no increased incidence of acute rejection. However, in one of the earlier studies at Stanford, the investigators demonstrated that a steroid-free immunosuppressive regimen could not be sustained in pediatric renal transplant recipients with recurrent glomerular disease (10). Disease recurrence accounts for 7–8% of all graft losses in pediatric kidney transplantation (Table 1) (11). As steroid therapy is utilized in many pediatric glomerulonephridities, it is important to know how the recent switch to steroid-free or rapid steroid taper regimens affects the prognosis of pediatric recipients with potentially recurrent disease. In this issue of Pediatric Transplantation, Chavers and her colleagues at the University of Minnesota report their experience with disease recurrence using a rapid discontinuation of prednisone regimen. These authors are in a unique position to discuss this issue, because the rapid discontinuation of corticosteroids has been used extensively and successfully for over 10 yr at the University of Minnesota (12). The authors retrospectively examined their experience with 74 patients, transplanted between 2002 and 2010, who received renal allografts under a rapid prednisone taper protocol. The authors identified 23 of the 74 patients (34%) who were at risk of recurrence and matched these patients with a historical control group of 69 patients managed with long-term steroids. In the control group, the authors identified 18 patients (26%) who were at risk of recurrence. The glomerulonephridities included focal segmental glomerulosclerosis (FSGS), IgA nephropathy, Henoch–Schonlein purpura (HSP) Pediatr Transplantation 2012: 16: 684–687 2012 John Wiley & Sons A/S.