title: Calcineurin inhibitor avoidance with daclizumab, mycophenolate mofetil, and prednisolone in DR-matched de novo kidney transplant recipients.
abstract: BACKGROUND
  Calcineurin inhibitor (CNI)-free regimens posttransplantation have been claimed to conserve graft function in addition to reduce the risk factors for cardiovascular and malignant disease in renal transplant recipients.
  
  
  METHODS
  The primary aim of this prospective, open-label, randomized, parallel-group, single-center study was to compare the effect of complete CNI-avoidance posttransplant (daclizumab + mycophenolate mofetil + prednisolone: Dac-group, n=27) with the standard CNI-based immunosuppressive protocol at our transplant unit (cyclosporine A + mycophenolate mofetil + prednisolone: CsA-group, n=27) on renal function (glomerular filtration rate [GFR] determined as plasma clearance of 51Cr-EDTA) in a selected low immunogenic risk population (DR-matched, PRA-negative de novo cadaveric transplant recipients).
  
  
  RESULTS
  There were no significant difference in GFR at week 10 (P=0.61), but GFR was significantly (P=0.029) lower in the Dac-group (52+/-20 ml/min) at month 12 than in the CsA-group (69+/-29 ml/min). One-year patient and graft survival did not differ between the two groups. Overall acute rejection rate was 70.4% (19/27) in the Dac-group and 29.6% (8/27) in the CsA-group (P=0.006).
  
  
  CONCLUSIONS
  The strategy to select DR-matched, PRA-negative de novo cadaveric transplant recipients for a CNI-avoidance protocol was not successful. The incidence of acute rejection was unacceptable high even though anti-CD25 antibody induction as well as initial higher mycophenolate mofetil doses (3 g/day) were applied, and renal function was significantly lower in the CNI-avoidance patients at 1 year. Other strategies need to be examined for avoidance of CNI's in the early posttransplant period.
authors.affiliation: Laboratory for Renal Physiology, Medical Department, Rikshospitalet, Oslo, Norway. anders.asberg@farmasi.uio.no
authors.forename: Anders
authors.initials: A
authors.lastname: Asberg
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
authors.forename: Pål D
authors.initials: PD
authors.lastname: Line
authors.forename: Janicke
authors.initials: J
authors.lastname: Narverud
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
authors.forename: Trond
authors.initials: T
authors.lastname: Jenssen
authors.forename: Anna V
authors.initials: AV
authors.lastname: Reisaeter
authors.forename: Linda F
authors.initials: LF
authors.lastname: Johnsen
authors.forename: Per
authors.initials: P
authors.lastname: Fauchald
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D000077561:Daclizumab; D003920:Diabetes Mellitus / Q000175:diagnosis; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006648:Histocompatibility; D006801:Humans; D006973:Hypertension / Q000175:diagnosis; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors; D014552:Urinary Tract Infections / Q000175:diagnosis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D008055:Lipids; D016572:Cyclosporine; D011239:Prednisolone; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus