Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients?
BACKGROUND
Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that has been shown to be superior to azathioprine in preventing early acute rejection in the general renal transplant population. However, it is uncertain whether these benefits also apply to older renal transplant recipients, who are known to be more susceptible to infectious complications and have considerably lower rates of rejection and immunological graft loss.


METHODS
A retrospective analysis was undertaken of all elderly (> or =55 years old) renal transplant recipients who underwent renal transplantation at the Princess Alexandra Hospital (1994-2000) and received either MMF (n=60) or azathioprine (n=55) in combination with prednisolone and cyclosporin. Data were analyzed on an intention-to-treat basis using a multivariate Cox proportional hazards model.


RESULTS
The azathioprine- and MMF-treated groups were well matched at baseline with respect to demographic characteristics, end-stage renal failure causes and transplant characteristics. Compared with the MMF cohort, azathioprine-treated patients experienced a shorter time to first rejection [hazard ratio (HR) 4.47, 95% CI 1.53-13.1, P<0.01]. However, azathioprine-treated patients were also less likely to develop opportunistic infections (HR 0.11, 95% CI 0.03-0.41, P=0.001). No differences were observed between the two groups with respect to hospitalization rates, intensive care admissions, hematological complications, or posttransplant malignancies. Actuarial 2-year survival rates for the azathioprine- and MMF-treated patients were 100 and 87%, respectively (P<0.001). The principal cause of death in the MMF cohort was infection. Using a multivariate Cox regression analysis of patient survival, an adjusted hazard ratio of 0.01 (95% CI 0.001-0.08, P=0.001) was calculated in favor of azathioprine. Overall graft survival also tended to be better in patients receiving azathioprine (HR 0.27, 95% CI 0.06-1.33, P=0.11),


CONCLUSIONS
In elderly renal transplant recipients, the combination of MMF, cyclosporin, and prednisolone appears to result in a worse outcome compared with the less potent combination of azathioprine, cyclosporin, and prednisolone. Future prospective studies need to specifically evaluate the risk/benefit ratios of newer, more potent immunosuppressive protocols, such as MMF-based regimens, in this important and sizeable patient subgroup.
Johnson
David W
DW
Renal Transplant Unit, Princess Alexandra Hospital1, Brisbane, Australia 4102.
Nicol
David L
DL
Purdie
David M
DM
Preston
John M
JM
Brown
Allison M
AM
Hawley
Carmel M
CM
Campbell
Scott B
SB
Wall
Darryl
D
Griffin
Anthony D
AD
Isbel
Nicole M
NM
D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007239:Infections / Q000453:epidemiology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine