title: Renal transplantation in children managed with lymphocyte depleting agents and low-dose maintenance tacrolimus monotherapy.
abstract: OBJECTIVE
  Describe the safety and efficacy of antithymocyte globulin or alemtuzumab preconditioning, steroid avoidance and reduced calcineurin inhibitor (CNI) immunosuppression in 34 children undergoing renal transplantation.
  
  
  METHODS
  ATG (n=8) or alemtuzumab (n=26) were infused at the time of transplantation. This was followed by low-dose twice a day tacrolimus monotherapy with consolidation to once daily dosing by 6 months and once every other day dosing by 12 months. Follow-up ranged from 0.5-2.9 years (mean 1.33 years), with a minimum of 6 months.
  
  
  RESULTS
  Both ATG and alemtuzumab were well tolerated. Lymphopenia occurred routinely and resolved after 3-6 months. Acute cellular rejection occurred in 9%; it was related to medical nonadherence in two patients and resulted in one graft loss at 1.5 years. Important adverse events included transient neutropenia in 10 children (none with serious infection), and autoimmune hemolytic anemia in two (resolved with a steroid course in both and conversion to sirolimus in one). Estimated glomerular filtration rate (e-GFR) was stable and averaged 88 mL/min/1.73 m2 at latest follow-up. Fifteen preadolescents had a greater increase in height Z-score at 1 year (1.3 vs. 0.5, P=0.001), and a higher e-GFR (94.8+/-21 vs. 76.6+/-20 ml/min/1.73 m2, P<0.05), when compared to case-matched historical controls who were weaned off steroids by 6 months after transplantation and received twice daily tacrolimus monotherapy.
  
  
  CONCLUSIONS
  This simple regimen appears safe, has a low risk for acute cellular rejection or other adverse effects, and is associated with excellent growth and renal function. Such a regimen may also improve compliance and limit CNI nephrotoxicity.
authors.affiliation: Children's Hospital of Pittsburgh, Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. ellisd@chp.edu
authors.forename: Demetrius
authors.initials: D
authors.lastname: Ellis
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Michael
authors.initials: M
authors.lastname: Moritz
authors.forename: Abhay
authors.initials: A
authors.lastname: Vats
authors.forename: Amit
authors.initials: A
authors.lastname: Basu
authors.forename: Henkie
authors.initials: H
authors.lastname: Tan
authors.forename: Liise
authors.initials: L
authors.lastname: Kayler
authors.forename: Janine
authors.initials: J
authors.lastname: Janosky
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Starzl
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D000740:Anemia / Q000453:epidemiology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007430:Intraoperative Care; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D011183:Postoperative Complications / Q000453:epidemiology; D016559:Tacrolimus / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D003404:Creatinine; D016559:Tacrolimus