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.