Background: Young transplant recipients benefit most from graft longevity, but are at high risk of rejection. Thus, in young recipients, the challenge is provision of effective immunosuppression resulting in good renal function while minimizing the toxicities of immunosuppressant therapy.
Methods: The following two case studies describe the clinical experience of achieving stable graft function in two young female transplant recipients of older living donor kidneys. As part of an ongoing clinical trial (A2307), immunosuppressant therapy consisted of everolimus (Certican) in combination with reduced-exposure cyclosporine (CsA) and prednisone.
Results: The two case studies demonstrate that rejection can be prevented and good, stable renal graft function achieved with everolimus 0.75-1.5 mg bid (long-term everolimus blood trough levels: 2.3-6.5 ng/ml in Case 1 and 3.8-9.3 ng/ml in Case 2) plus reduced-exposure CsA. CsA was reduced from an initial dose of 100 mg bid (C2 target levels of 500-700 ng/ml) to 75 mg and 35 mg bid in the two cases, respectively, in order to reach maintenance C2 target levels of 230-450 ng/ml. Maintenance prednisone dose was low in both cases (7-7.5 mg/day). Both patients tolerated the immunosuppressant regime well, and at 31-33 months follow-up they remained free of acute rejection episodes and toxicities associated with CsA.
Conclusion: Everolimus plus reduced-dose CsA can provide safe, adequate immunosuppression resulting in prevention of acute rejection in young recipients. Reducing CsA exposure minimizes risk of nephrotoxicity and other adverse events that affect compliance in these patients for whom long-term graft survival is vital.