Cyclosporine withdrawal improves long-term graft survival in renal transplantation.
BACKGROUND
The reduction in renal transplant rejection rates achieved over the last 20 years have not translated into a commensurate improvement in long-term graft survival. Cyclosporine has been central to immunosuppressive regimens throughout this period but its effect on long-term transplant outcomes remains unclear.


METHODS
This randomized controlled trial allocated first cadaveric renal transplant recipients in seven centers around Australia to three immunosuppressive regimens: azathioprine and prednisolone (AP), long-term cyclosporine alone (Cy), or cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL).


RESULTS
Between 1983 and 1986, 489 patients were randomized with 98% follow-up to a median of 20.6 years. Mean graft survival (censoring deaths) was superior in the WDL group (14.8 years) when compared with both AP (12.4 years, P=0.01 log-rank test) and Cy (12.5 years, P=0.01 log-rank test) groups by intention-to-treat. Without death censoring, graft survival with WDL was superior to AP (9.5 years vs. 6.7 years, P=0.04) and of borderline superiority to Cy (9.5 years vs. 8.5 years, P=0.06). Patient survival was not different between the three groups. Renal function was superior in AP (at 1, 10, and 15 years posttransplant) and WDL (at 1, 5, 10, 15, and 20 years) groups when compared with Cy.


CONCLUSIONS
This study illustrates superior long-term renal transplant survival and preservation of renal function with a protocol using cyclosporine withdrawal. If long-term renal transplant outcomes are to improve, we should reconsider guidelines recommending universal maintenance use of cyclosporine.
Gallagher
Martin
M
Renal Division, The George Institute For International Health, Camperdown, NSW, Australia. mgallagher@george.org.au
Jardine
Meg
M
Perkovic
Vlado
V
Cass
Alan
A
McDonald
Stephen
S
Petrie
James
J
Eris
Josette
J
D001379:Azathioprine / Q000627:therapeutic use; D002423:Cause of Death; D016572:Cyclosporine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D009369:Neoplasms / Q000453:epidemiology; D018579:Patient Selection; D011239:Prednisolone / Q000627:therapeutic use; D016019:Survival Analysis; D017741:Survivors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D001379:Azathioprine