Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.
BACKGROUND
A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years.


METHODS
Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years.


RESULTS
The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF.


CONCLUSIONS
All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.
Ahsan
N
N
Milton S. Hershey Medical Center, Hershey, PA 17104-1696, USA.
Johnson
C
C
Gonwa
T
T
Halloran
P
P
Stegall
M
M
Hardy
M
M
Metzger
R
R
Shield
C
C
Rocher
L
L
Scandling
J
J
Sorensen
J
J
Mulloy
L
L
Light
J
J
Corwin
C
C
Danovitch
G
G
Wachs
M
M
VanVeldhuisen
P
P
Salm
K
K
Tolzman
D
D
Fitzsimmons
W E
WE
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use*; D044383:Black People; D002102:Cadaver; D002648:Child; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000209:etiology; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D007683:Kidney Tubular Necrosis, Acute / Q000453:epidemiology / Q000473:pathology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology; D015996:Survival Rate; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors; D014481:United States; D044465:White People; D001741:Black or African American
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D007328:Insulin; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus