Pediatric renal transplantation is safe without steroids. Daclizumab first-dose doubling and extended use for 6 months replaces steroids effectively without evidence of overimmunosuppression and may be the pivotal cause for the reduced acute rejection seen in this trial. This pilot study provides preliminary data to test this protocol in a prospective, multicenter randomized study.
Pediatric allograft ASK biopsies can be performed with minimal adverse outcomes. Transperitoneal ASK placement is not a contraindication for percutaneous biopsy. Strategies to improve biopsy safety include recommendations for patient positioning for transperitoneal ASKs, improved techniques for real-time ultrasound guidance, and use of finer gauge needles.
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.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.