Over the last few decades, the long-term survival of renal allografts has significantly increased. Despite this success, a substantial number of renal allograft recipients eventually require the permanent reinstitution of renal replacement therapy because of allograft failure . As an example, approximately 13 percent of patients who received a renal allograft in 2006 had undergone a previous transplant . In addition, among over 100,000 patients beginning dialysis in 2002, 4 percent had a failed renal allograft [2,3].
The survival of such patients on dialysis appears to be relatively poor [4-7]. In a study of 4743 renal transplant recipients in Canada, for example, the risk of death was significantly higher with allograft failure versus those with continued allograft function (adjusted hazard ratio 3.4, 95% CI 2.75-4.2) .
The reinstitution of dialysis after renal transplant failure presents the clinician with the dilemma of whether to withdraw immunosuppressive medications and, if withdrawal is initiated, the optimal method of tapering such therapy. The issues that must be addressed with the withdrawal of immunosuppression after renal transplant failure are reviewed in this topic review.
REASONS FOR WITHDRAWAL
The most compelling reasons to withdraw immunosuppressive medications in dialysis patients with a failed renal transplant are the increased risk of infection, malignancy, and complications associated with long-term corticosteroid immunosuppression use. Infection is the second leading cause of death in this setting . Another problem is that the dosing of some immunosuppressive agents is difficult in patients with renal failure.
Increased risk of infection — An increased risk of serious infections is observed in both transplant recipients (because of the direct effects of immunosuppressive medications) and dialysis patients (because of immune system derangements from uremia and access-related problems). These factors contribute to the unacceptably high incidence of infection in dialysis patients who continue to receive immunosuppressive medications after a renal allograft has failed [9-11]: