Purpose: Calcineurin inhibitors (CNIs) are the mainstay of immunotherapy after heart transplantation. Unfortunately CNIs are associated with renal dysfunction due to nephrotoxic side effects. The proliferation signal inhibitors (PSIs) have been demonstrated to reduce cardiac allograft vasculopathy (CAV) but they may potentiate the nephrotoxic effects of CNIs. In recent renal sparing protocols, PSIs are initiated with gradual tapering off of CNI while maintaining mycophenolate. It is not clear as to whether time after heart transplant is related to safety and efficacy of the renal sparing protocol. It is believed that earlier renal sparing protocol (RSP) post-transplant may encourage more dysfunction prior to benefit.

Methods: Between 1994 and 2011, 76 patients were initiated on the renal sparing protocol with gradual tapering of CNI and institution of PSI with maintenance of MMF. Patients were divided into time post-transplant that the renal sparing protocol was initiated: 0-5years, 5-10 years and >10 years post-transplant. Serum creatinine was measured at baseline, 1, 3, 6 and 12 months after initiation of the renal sparing protocol.

Results: There was improvement in renal function regardless of when patients initiated the renal sparing protocol. There is also no significant difference between all three groups in terms of one year subsequent actuarial freedom from any treated rejection, treated cellular rejection and treated antibody mediated rejection. However, patients who initiated RSP 0-5 years post-transplant were more likely to fail and return to a maintenance immunosuppression regimen including a CNI. (See table)

Conclusion: RSP appears to be equally effective at all time-points after heart transplantation, but caution should be taken if initiated earlier after transplant.

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