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Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients?
David W Johnson1, David L Nicol, David M Purdie
1Renal Transplant Unit, Princess Alexandra Hospital1, Brisbane, Australia 4102.
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.
Insights
In elderly kidney transplant patients, azathioprine showed better survival and fewer infections than mycophenolate mofetil (MMF). MMF use was linked to higher mortality, primarily due to infection, suggesting azathioprine may be a safer choice for this population.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation Medicine
Background:
- Mycophenolate mofetil (MMF) is a potent immunosuppressant superior to azathioprine in general renal transplant recipients.
- Efficacy and safety of MMF in elderly renal transplant recipients, who are prone to infections and have lower rejection rates, remain uncertain.
Purpose of the Study:
- To compare the outcomes of elderly renal transplant recipients treated with MMF versus azathioprine.
- To evaluate the impact of MMF-based immunosuppression on rejection rates, infections, and survival in older patients.
Main Methods:
- Retrospective analysis of elderly (≥55 years) renal transplant recipients from 1994-2000.
- Patients received either MMF (n=60) or azathioprine (n=55) combined with prednisolone and cyclosporin.
- Intention-to-treat analysis using a multivariate Cox proportional hazards model.
Main Results:
- Azathioprine group had shorter time to first rejection (HR 4.47, P<0.01) but fewer opportunistic infections (HR 0.11, P=0.001).
- Actuarial 2-year survival was 100% for azathioprine vs. 87% for MMF (P<0.001), with infection as the main cause of death in the MMF group.
- Multivariate analysis favored azathioprine for patient survival (aHR 0.01, P=0.001); graft survival also trended better with azathioprine (HR 0.27, P=0.11).
Conclusions:
- In elderly renal transplant recipients, MMF combined with prednisolone and cyclosporin resulted in worse outcomes than azathioprine-based regimens.
- Azathioprine demonstrated superior patient survival and a lower incidence of opportunistic infections in this specific patient subgroup.
- Further prospective studies are needed to assess the risk/benefit of potent immunosuppressive protocols like MMF in elderly transplant recipients.