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Growth and renal function after steroid-free tacrolimus-based immunosuppression in children with renal transplants
1Children's Hospital of Pittsburgh, Department of Pediatrics, University of Pittsburgh School of Medicine, PA 15213, USA.
Insights
Steroid withdrawal after pediatric kidney transplantation improves child growth and maintains renal function. This approach, using tacrolimus-based immunosuppression, shows promising results with low rates of graft loss.
Area of Science:
- Pediatric Nephrology
- Transplantation Immunology
- Growth and Development
Background:
- Steroid withdrawal post-renal transplantation can enhance growth in children but is limited by high rejection rates with older immunosuppression protocols.
- Tacrolimus-based immunosuppression offers a potential alternative for managing steroid withdrawal in pediatric kidney transplant recipients.
Purpose of the Study:
- To evaluate the impact of steroid withdrawal within one year of renal transplantation on growth and renal function in children on tacrolimus-based immunosuppression.
- To assess the safety and efficacy of steroid withdrawal in pediatric kidney transplant recipients.
Main Methods:
- A study involving 52 children undergoing renal transplantation and tacrolimus-based immunosuppression, with steroid withdrawal within one year.
- Assessment of height Z-score, weight-for-height index (WHI), body mass index (BMI), graft loss, and calculated creatinine clearance (glomerular filtration rate - GFR).
- Children were stratified into three age groups at transplantation: 0-5 years, 6-12 years, and 13-16 years.
Main Results:
- Significant height improvement was observed in younger (0-5 years) and adolescent (13-16 years) groups, with Z-scores increasing by over 1.5 standard deviations at 3 years post-transplant.
- Weight-for-height index and body mass index showed improvements, with no indication of obesity after adjusting for height age.
- Steroid withdrawal failure occurred in 13% of children, but overall rates of renal dysfunction and graft loss over 3 years were lower compared to children who did not undergo steroid withdrawal (P<0.05).
- Mean glomerular filtration rate remained stable and within the normal range (96-102 ml/min/1.73 m2) across all groups throughout the 3-year follow-up.
Conclusions:
- Steroid withdrawal in pediatric kidney transplant recipients on tacrolimus-based immunosuppression effectively normalizes growth without inducing obesity.
- This strategy is associated with acceptable rates of graft dysfunction or loss and may even reduce these risks compared to continuous steroid use.
- Steroid withdrawal is a viable option for improving long-term outcomes in pediatric kidney transplantation.
Abstract:
Steroid withdrawal after renal transplantation and cyclosporine-based immunosuppression enhances growth in children, but this practice is not widely employed because of a 50%-60% rate of rejection, graft dysfunction, or graft loss. The current study evaluates growth and renal function after withdrawal and discontinuation of steroids within 1 year of transplantation in 52 children receiving tacrolimus (FK-506)-based immunosuppression. Height Z-score, weight-for-height index (WHI), and body mass index (BMI), as well as graft loss and calculated creatinine clearance as a measure of glomerular filtration rate (GFR), were assessed. Children were divided into three groups according to age at transplantation: group I, 16 children aged 0-5 years; group II, 17 children aged 6-12 years; group III, 19 children aged 13-16 years. Significant and sustained improvement in height occurred in groups I and III, with Z-scores increasing by 1.51 and 1.57 standard deviations at 3 years after transplantation compared with the Z-score at transplantation (P<0.02). Mean WHI values remained near 100% in groups I and III, and significantly increased above 100% only in group II at 2 years after transplantation. Although actual BMI scores improved significantly in groups II and III at both 2 and 3 years post transplantation (P<0.05), when BMI scores were adjusted for height age, none of these groups had values >95% denoting obesity. Failure of steroid withdrawal, defined as reinstitution of steroids, graft dysfunction, or graft loss, occurred in 9 of 68 (13%) children who underwent steroid withdrawal at any time after transplantation, and resulted in graft dysfunction or graft loss in 5 (7%). Over a 3-year period, rates of renal dysfunction, as manifested by >50% rise in the serum creatinine level above baseline, or graft loss were lower in these 68 children compared with 8 children who never had steroid withdrawal (P<0.05). Mean GFR at 3 years after transplantation ranged from 96 to 102 ml/min per 1.73 m2 in all three steroid withdrawal groups, and remained stable during the 3 years of follow-up. These data indicate that steroid withdrawal enables normalization of growth without obesity, and without imposing an excessive risk for graft dysfunction or graft loss.