Corticosteroid avoidance in pediatric renal transplantation: can it be achieved?

Abstract

Corticosteroids have been a cornerstone therapy in renal transplantation, which is the treatment modality of choice for adult and pediatric end-stage renal disease. Their use is associated with significant morbidity, notably cardiovascular, endocrine, and bone complications, body disfiguration, and almost universal growth retardation in children. While newer immunosuppressants have reduced the incidence of these adverse effects, they continue to pose significant post-transplant challenges. There are various strategies that can be used to avoid these adverse effects including the use of an alternative corticosteroid such as deflazacort, minimization of corticosteroid dosage, corticosteroid withdrawal after a period of early use, and more recently complete corticosteroid avoidance. Recent randomized studies have demonstrated significant improvement in growth parameters, lipid profile, and in the amount of bone loss in patients treated with deflazacort, an oxazoline analog of prednisone, compared with methylprednisone.Corticosteroid minimization has been associated with an increased rate of acute rejection. While augmentation with newer immunosuppressants has helped reduce the incidence of acute rejection, significant improvements in growth have not been demonstrated. Alternate-day corticosteroid therapy has been shown to have a beneficial effect on growth but regimen compliance has limited its widespread applicability. Studies of corticosteroid withdrawal have met with varied success. Early corticosteroid withdrawal has been associated with rejection rates ranging from 10% to 81% and late corticosteroid withdrawal, from 13% to 68.8%, with acute rejection episodes occurring as late as 4 years after corticosteroid withdrawal. The rates of clinical acute rejection have been unacceptably high, and corticosteroid withdrawal is thus used very sparingly in adults and even less so in children. Complete corticosteroid avoidance as reported by an initial study has been associated with a 23% incidence of acute rejection and 'catch-up' growth post-transplantation in 14 pediatric recipients, as measured by the change in height standard deviation scores post-transplantation. A second renal transplant study, in adults, demonstrated similar rejection rates of 25% with improvement in post-transplant hypertension and lipid profiles. A more recent pediatric study using a novel extended daclizumab induction protocol demonstrated an 8% incidence of clinical acute rejection with significant improvements in graft function, hypertension, and growth, without an increased incidence of infectious complications. Renal transplantation with a corticosteroid-free protocol may offer significant advantages in the incidence of acute rejection, graft function, growth, blood pressure, lipidemia, and body appearance and appears to be well tolerated when used with a variety of current induction protocols to replace early corticosteroid use. This protocol may also be applicable to other areas of solid organ transplantation in all age groups.