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

Transplantation. 2001 Jul 27;72(2):245-50. doi: 10.1097/00007890-200107270-00014.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antilymphocyte Serum / therapeutic use
  • Azathioprine / therapeutic use*
  • Black People
  • Black or African American
  • Cadaver
  • Child
  • Cross-Over Studies
  • Cyclosporine / administration & dosage
  • Cyclosporine / therapeutic use*
  • Diabetes Mellitus / etiology
  • Drug Monitoring
  • Drug Therapy, Combination
  • Graft Rejection / drug therapy
  • Graft Rejection / epidemiology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Graft Survival / immunology*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use*
  • Insulin / therapeutic use
  • Kidney Function Tests
  • Kidney Transplantation / immunology
  • Kidney Transplantation / mortality
  • Kidney Transplantation / physiology*
  • Kidney Tubular Necrosis, Acute / epidemiology
  • Kidney Tubular Necrosis, Acute / pathology
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use*
  • Postoperative Complications / classification
  • Postoperative Complications / epidemiology
  • Survival Rate
  • Tacrolimus / blood
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Tissue Donors
  • United States
  • White People

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Insulin
  • Cyclosporine
  • Mycophenolic Acid
  • Azathioprine
  • Tacrolimus