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

Am J Transplant. 2021 Jan;21(1):123-137. doi: 10.1111/ajt.16005. Epub 2020 Jun 27.


CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant 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% vs 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 = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs 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 kidney transplant recipients. NCT01544491.

Keywords: clinical research/practice; glomerular filtration rate (GFR); graft survival; immunosuppressant-mechanistic target of rapamycin: everolimus; immunosuppressive regimens-minimization/withdrawal; kidney transplantation/nephrology; patient safety.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Everolimus
  • Glomerular Filtration Rate
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Graft Survival
  • Humans
  • Immunosuppressive Agents
  • Kidney Transplantation* / adverse effects
  • Mycophenolic Acid / therapeutic use
  • Steroids
  • Tacrolimus*
  • Transplant Recipients


  • Immunosuppressive Agents
  • Steroids
  • Everolimus
  • Mycophenolic Acid
  • Tacrolimus

Associated data