Growth and renal function after steroid-free tacrolimus-based immunosuppression in children with renal transplants

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.

Report of an NIH task force on research priorities in chronic kidney disease in children

“…An approach to ensuring normal final adult height in infants, children, and adolescents with CRI and ESRD should include assuring that patients are at the 50th percentile for mid-parental height at transplantation, that they have optimal allograft function post-transplant, that a steroid-avoidance or steroid-withdrawal immunosuppression study is considered, and that time on dialysis is limited or that they receive preemptive transplantation [45]. A research question is whether routine rhGH treatment should be provided to optimize the pubertal growth spurt in all children with CRI and ESRD.…”

Effect of Renal Graft on Longitudinal Growth in Prepubertal Children

“…Accelerated or catch-up growth was defined as the change in hSDS (∆hSDS) ≥ + 0.5 SD/y. 12 The patients were divided into 2 groups according to the increase in height standard deviation scores over the first 2 years after renal transplant: group 1 (increases in height standard deviation scores < 1) and group 2 (increases in height standard deviation scores > 1).…”

Selective late steroid withdrawal after renal transplantation

“…The benefit of SW on growth (i.e. catch-up growth) and body mass index (BMI) is predominantly observed in prepubertal children [5,9]. Thus, no consensus has been reached in the paediatric community concerning steroid elimination [14] or preservation [15] after renal RTPL.…”

“…Protocols with steroid withdrawal (SW) either early (5 days to 12 months) [4][5][6][7] or late (≥12 months) after RTPL [8,9], or even steroid-free protocols [10,11] have been proposed. These protocols included induction therapy with thymoglobulin or specific interleukin (IL)-2 receptor blockers [4][5][6][7][8]11] and/or were tacrolimus (Tac) based [4,5,7,8,10,11]. So far, only one study has reported successful SW in paediatric patients receiving cyclosporine A (CyA) maintenance immunosuppression without induction therapy [9].…”