Immunosuppression in live-related donor renal transplantation

Abstract

Background: Triple immunosuppression with cyclosporine, azathioprine and prednisolone is the most common regimen employed following renal transplantation. No information is available regarding its impact on the results of renal transplantation in India. The present study is an audit of a fixed-dose cyclosporine-based immunosuppressive regimen in an exclusively live-related donor transplant programme, with specific regard to graft and patient outcomes.

Methods: Patients transplanted over a 3-year period and receiving cyclosporine-based immunosuppression were studied. The relationship between immunosuppression and graft outcomes [rejection episodes (RE), graft function, graft survival], and patient outcomes (patient survival) was analysed in those receiving triple immunosuppression. Dosage schedules were audited. Cyclosporine trough level monitoring was employed at graft dysfunction episodes, or at dose reduction points.

Results: The median follow up was 14 months. Triple drug immunosuppression was used in 191 patients and double drug therapy in 26. The overall one-year patient survival rate was 91% and the corresponding graft survival rate was 90%. An audit of dosing schedules showed that over the first 6 months post-transplant, cumulatively, 20%-50% of patients received azathioprine, and 55%-60% received cyclosporine in doses below the protocol. The immunosuppressive doses (both of cyclosporine and azathioprine) in the first month were significantly related to the RE (p < 0.01) in the first month and the total number of RE in the first 6 months (p < 0.01). The other predictors were younger recipient age and older donor age. The sixth-month serum creatinine level was predicted by the donor age, the level of serum creatinine in the first month and the total number of RE in the first 6 months post-transplant. While no specific predictors of graft loss were identified in this cohort, diabetic nephropathy (p = 0.000) as the native renal disease, and the total number of RE were strongly related to patient mortality. The occurrence of > or = 2 RE in the first 6 months was an independent predictor, increasing the risk of death in the first 2 years post-transplant by 2.3 (p = 0.0001, 95% CI: 1.5-3.4).

Conclusions: Sub-therapeutic baseline immunosuppression in the early post-transplant period predisposes to acute RE. This has an impact not only on graft function but also forms an important proximate marker of mortality, as seen in this cohort. Thus, immunosuppressive drug dosage should be optimized and therapeutic drug level monitoring strategies should be preemptive rather than event related, especially in the early post-transplant period. While fixed-dose immunosuppressive drug schedules are widely followed, it is possible to fall short of the target unless a specific effort is made to meet and sustain schedules.