Mycophenolate Mofetil/Sirolimus Compared to Other Common Immunosuppressive Regimens in Kidney Transplantation
TR Srinivas, JD Schold, G Guerra, A Eagan, CM Bucci, HU Meier-Kriesche
Am J Transplant. 2007;7:586-594
Summary
This retrospective review of registry data from 2000 to 2005 examined the outcomes after renal transplantation among patients taking different immunosuppressive regimens. The combination of sirolimus and mycophenolate mofetil (SRL/MMF) was compared with other combinations, including tacrolimus/mycophenolate mofetil (TAC/MMF), cyclosporine/mycophenolate mofetil (CSA/MMF), tacrolimus/sirolimus (TAC/SRL), and cyclosporine/sirolimus (CSA/SRL). More than 58,000 patients (the SRL/MMF group included 2040 [3.5%] patients) were included in this study that examined a comprehensive set of analyses. All analyses pointed to the unequivocal inferiority of the SRL/MMF combination. SRL/MMF was associated with inferior patient survival, inferior graft survival, a higher incidence of acute rejection, and a higher rate of delayed graft function when compared with TAC/MMF (by 2005, TAC/MMF use accounted for 80% of the patients undergoing renal transplantation).
Viewpoint
Even when the limitations of retrospective registry analyses are taken into account, this paper makes a dramatic statement. Many of the concerns in renal transplant patients today involve the long-term nephrotoxicity associated with calcineurin inhibitors (CIs); thus, the substantial interest in CI avoidance. Unfortunately, this article makes the point that complete CI avoidance, using the seemingly potent combination of SRL and MMF, is associated with significantly inferior outcomes. These findings held up in all subgroup analyses, including patients receiving antibody induction, living donor cases, and extended criteria donors. This article should serve as a sobering wake-up call for those trying to do away with CIs.