Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal.

: CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4-6 weeks post-transplantation to receive everolimus+reduced-exposure tacrolimus (EVR+rTAC; N=52) with corticosteriod withdrawal at 6-month post-transplantation or continue mycophenolate mofetil+standard-exposure TAC (MMF+sTAC; N=54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at Month 36 was 9.8% versus 9.6% (difference: 0.2%; 80% confidence interval: -7.3 to 7.7) for EVR+rTAC and MMF+sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at Month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m2 ). Mean changes (z-score) in height (0.72 vs 0.39; P=0.158) and weight (0.61 vs 0.82; P=0.453) from randomization to Month 36 were comparable, while growth in pre-pubertal patients on EVR+rTAC was better (P=0.050) versus MMF+sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR+rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR+rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric KTRs.