Calcineurin inhibitor avoidance with daclizumab, mycophenolate mofetil, and prednisolone in DR-matched de novo kidney transplant recipients.
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.
Asberg
Anders
A
Laboratory for Renal Physiology, Medical Department, Rikshospitalet, Oslo, Norway. anders.asberg@farmasi.uio.no
Midtvedt
Karsten
K
Line
Pål D
PD
Narverud
Janicke
J
Holdaas
Hallvard
H
Jenssen
Trond
T
Reisaeter
Anna V
AV
Johnsen
Linda F
LF
Fauchald
Per
P
Hartmann
Anders
A
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
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