Corticosteroid-free Kidney Transplantation Improves Growth: 2-Year Follow-up of the TWIST Randomized Controlled Trial

Transplantation. 2015 Jun;99(6):1178-85. doi: 10.1097/TP.0000000000000498.

Abstract

Background: Corticosteroid withdrawal (CW) after pediatric kidney transplantation potentially improves growth while avoiding metabolic and other adverse events. We have recently reported the results of a 196 subject randomized controlled trial comparing early CW (tacrolimus, mycophenolate mofetil (MMF), daclizumab, and corticosteroids until day 4) with tacrolimus, MMF, and corticosteroid continuation (CC). At 6 months, CW subjects showed better growth with no adverse impact on acute rejection or graft survival (Am J Transplant 2010; 10: 828-836). This 2-year investigator-driven follow-up study aimed to determine whether improved growth persisted in the longer term.

Methods: Data regarding growth, graft outcomes and adverse events were collected at 1 year (113 patients) and 2 years (106 patients) after transplantation. The primary endpoint, longitudinal growth calculated as delta height standard deviation score, was analyzed using a mixed model repeated measures model.

Results: Corticosteroid withdrawal subjects grew better at 1 year (difference in adjusted mean change, 0.25; 95% confidence interval, 0.10, 0.40; P = 0.001). At 2 years, growth remained numerically better in CW subjects (0.20 (-0.01, 0.41); P = 0.06), and significantly better in prepubertal subjects (0.50 (0.16, 0.84); P = 0.004). Bacterial and viral infection was significantly more common in CW subjects at 1 year only. Corticosteroid withdrawal and CC subjects received similar exposure to both tacrolimus and MMF at 1 and 2 years. No significant difference in patient or graft survival, rejection, estimated glomerular filtration rate, or other adverse events was detected.

Conclusion: Early CW effectively and safely improves growth up to 2 years after transplantation, particularly in prepubertal children.

Publication types

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

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Child
  • Child Development / drug effects
  • Child, Preschool
  • Daclizumab
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Graft Rejection
  • Graft Survival / drug effects
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Male
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives
  • Tacrolimus / administration & dosage

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Daclizumab
  • Mycophenolic Acid
  • Tacrolimus