Avoidance of cyclosporine in renal transplantation: effects of daclizumab, mycophenolate mofetil, and steroids.
Cyclosporine (CsA) has been implicated in both acute and chronic graft dysfunction. The addition of humanized IL-2 receptor antibody daclizumab (DZB) to CsA-based immunosuppression decreases the rate of acute renal transplant rejection. Therefore, 45 patients were evaluated in an immunosuppressive protocol that included DZB, mycophenolate mofetil (MMF), and steroids without CsA. This was a prospective, nonrandomized, open-label trial of the efficacy and safety of the treatment. DZB was given intravenously at 2 mg/kg before transplantation and then at 1 mg/kg every 2 wk for four doses, MMF was given orally at 3 g/d, and methylprednisolone/prednisone was given at 7 mg/kg per day and tapered to 15 mg/d at 6 mo. CsA was added to the regimen when patients developed acute rejection episodes or adverse effects to steroids or MMF; 49% of patients were spared CsA maintenance. Patients without CsA had lower serum creatinine at 6 mo and needed fewer medications to control BP. Incidence of biopsyproven rejections was 31% and occurred early (median, 10 d). These rejection episodes occurred earlier in cadaver transplants (median, 7 d) and later in living donor transplants (median, 62 days). Acute rejections occurred at a higher frequency (46% versus 34%) and earlier (6.5 versus 15 d) in patients with delayed graft function compared with patients without delayed graft function. Most of the rejections were moderate and easily reversible. The actuarial 1-yr graft survival was 95% with 100% patient survival.
Tran
Huong T B
HTB
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Internal Medicine, Ho Chi Minh City University of Medicine and Pharmacy, Viet Nam.
Acharya
Muralidhar K
MK
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
McKay
Dianne B
DB
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Sayegh
Mohamed H
MH
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Carpenter
Charles B
CB
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Auchincloss
Hugh
H
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Kirkman
Robert L
RL
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Milford
Edgar L
EL
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016572:Cyclosporine / Q000627:therapeutic use; D000077561:Daclizumab; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000503:physiopathology; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011446:Prospective Studies; D019233:Retreatment; D013256:Steroids / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D000077561:Daclizumab; D009173:Mycophenolic Acid