title: Corticosteroid-free Kidney Transplantation Improves Growth: 2-Year Follow-up of the TWIST Randomized Controlled Trial.
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.
  
  
  CONCLUSIONS
  Early CW effectively and safely improves growth up to 2 years after transplantation, particularly in prepubertal children.
authors.affiliation: 1 Department of Paediatric Nephrology, Royal Manchester Children's Hospital,Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. 2 Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom. 3 Research and Innovation Department, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. 4 Centre for Biostatistics, University of Manchester, Manchester, United Kingdom. 5 Department of Nephrology, Kidney Transplantation and Hypertension, Children's Memorial Health Institute, Warsaw, Poland. 6 Department of Paediatric Nephrology, Great Ormond Street Hospital, London, United Kingdom. 7 Department of Paediatric Nephrology, Nottingham University Hospitals, Nottingham, United Kingdom. 8 Department of Paediatric Nephrology, Leeds General Infirmary, Leeds, United Kingdom. 9 Department of Paediatric Nephrology, University Hospital Motol, Prague, Czech Republic. 10 Department of Paediatric Nephrology, Royal Hospital for Sick Children, Glasgow, United Kingdom. 11 Department of Paediatric Nephrology, Semmelweis University of Medicine, Budapest, Hungary. 12 Department of Pediatric Nephrology, Universitair Ziekenhuis KU Leuven, Belgium. 13 Department of Paediatric Nephrology, Birmingham Children's Hospital, Birmingham, United Kingdom. 14 Department of Pediatrics, Cliniques Universitaires Saint-Luc, Université catholique de Louvain Medical School, Brussels, Belgium. 15 Department of Pediatric Nephrology, Hopital Femme Mere Enfant, Lyon, France. 16 Department of Paediatric Nephrology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom. 17 Department of Paediatrics, Azienda Ospedaliera di Padova, Padova, Italy. 18 Department of Pediatric Nephrology, Red Cross Children's Hospital, Cape Town, South Africa. 19 Department of Paediatrics I, University Children's 
authors.forename: Nicholas J A
authors.initials: NJ
authors.lastname: Webb
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authors.forename: Karel
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authors.forename: Jeno
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authors.lastname: Jaray
authors.forename: Rita
authors.initials: R
authors.lastname: Van Damme-Lombaerts
authors.forename: David V
authors.initials: DV
authors.lastname: Milford
authors.forename: Nathalie
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authors.lastname: Godefroid
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authors.forename: Mignon
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authors.forename: Burkhard
authors.initials: B
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mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D000077561:Daclizumab; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016559:Tacrolimus / Q000008:administration & dosage
chemical_list: D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus