Corticosteroid avoidance in pediatric renal transplantation

Abstract

Corticosteroids have played a central role in the evolution of renal transplant as the modality of choice for renal replacement in end stage kidney disease. Their use is associated with significant, dose related morbidity including osseous, cardiovascular, metabolic complications, body disfigurement and growth retardation in children. The strategies that have been employed to minimize these side effects include reduction in the daily administered dose of steroids, use of alternate day dosing regimens, steroid withdrawal post-transplantation and complete steroid avoidance. Steroid dose minimization has been associated with increased rates of acute rejection, though introduction of newer and more potent immunosuppressives has helped reduce the incidence of this complication. Steroid minimization will benefit patient morbidity due to cataracts, cardiovascular and osseous complications, but may offer little benefit towards improving linear growth. Alternate day steroid therapy may have a greater impact on growth improvement, but may be troubled by regimen non-adherence. Steroid withdrawal post-transplant, the ultimate target, is successful in a cohort of patients, but overall, has been historically associated with unacceptably high rates of clinical acute rejection, and has thus been used sparingly in adults and even less so in children. Complete corticosteroid avoidance, using newer induction and immunosuppressive agents, has been associated with an 8-23% incidence of acute rejection in pediatric renal transplant patients, significant catch-up growth post-transplant, improvements in post-transplant hypertension and hyperlipidemia, and a high safety profile at current follow-up. Newer induction protocols may allow complete steroid-free immunosuppression thus offering significant advantages in preventing the above-mentioned steroid related morbidity, which could also possibly be applicable to other areas of solid organ transplantation in all age groups.

Steroid elimination is coming of age

“…Although these data give us clues about post-transplant timing and the recipients most likely to succeed with steroid tapering, confidence in eliminating steroids from chronic immunosuppression remains low, because there is too much of an unknown risk of rejection and graft loss in an age group for which, in fact, long-term graft outcome may be the best [13]. Some recent steroid minimization studies have been summarized in a recent review in which the lack of uniformity in maintenance and induction agent therapies is very apparent [14]. The desirable patient and graft outcomes results from the largest pediatric single-center trial of complete steroid avoidance hold promise for more general applicability for pediatric recipients of all ages, with the promise of unprecedented trends in catch-up growth [4].…”

Historical review and perspectives in pediatric transplantation

“…Complete corticosteroid avoidance, using newer induction and immunosuppressive agents, has been associated with an 8-23% incidence of acute rejection, significantly better growth catch-up after transplant, improvement in posttransplant hypertension and hyperlipidemia, and a high safety profile at follow-up [44 ]. Safety was confirmed in a pediatric population receiving daclizumab, tacrolimus, and mycophenolate mofetil and no steroids at any time after transplant [45 ].…”

Therapy Insight: orthopedic complications after solid organ transplantation in childhood

“…73 In renal transplant patients the success rate is much lower. 74 Steroid withdrawal can increase the risk of rejection, and necessitate higher dosing of nephrotoxic drugs such as ciclosporin and tacrolimus. Every-other-day dosing is used in many centers; however, no threshold dose has been defined and there is great variation in corticosteroid metabolism between individuals.…”