Calcineurin inhibitor sparing strategies in renal transplantation, part one: Late sparing strategies  

作　　者：Andrew Scott Mathis Gwen Egloff Hoytin Lee Ghin 

机构地区：[1]Pharmacy Department,Monmouth Medical Center,Long Branch,NJ 07740,United States [2]School of Pharmacy,University of Connecticut,Storrs,CT 06268,United States

出　　处：《World Journal of Transplantation》2014年第2期57-80,共24页世界移植杂志

摘　　要：Kidney transplantation improves quality of life and reduces the risk of mortality. A majority of the success of kidney transplantation is attributable to the calcineurin inhibitors(CNIs), cyclosporine and tacrolimus, and their ability to reduce acute rejection rates. However, longterm graft survival rates have not improved over time, and although controversial, evidence does suggest a role of chronic CNI toxicity in this failure to improve outcomes. Consequently, there is interest in reducing or removing CNIs from immunosuppressive regimens in an attempt to improve outcomes. Several strategies exist to spare calcineurin inhibitors, including use of agents such as mycophenolate mofetil(MMF), mycophenolate sodium(MPS), sirolimus, everolimus or belatacept to facilitate late calcineurin inhibitor withdrawal, beyond 6 mo post-transplant; or using these agents to plan early withdrawal within 6 mo; or to avoid the CNIs all together using CNI-free regimens. Although numerous reviews have been written on this topic, practice varies significantly between centers. This review organizes thedata based on patient characteristics(i.e., the baseline immunosuppressive regimen) as a means to aid the practicing clinician in caring for their patients, by matching up their situation with the relevant literature. The current review, the first in a series of two, examines the potential of immunosuppressive agents to facilitate late CNI withdrawal beyond 6 mo post-transplant, and has demonstrated that the strongest evidence resides with MMF/MPS. MMF or MPS can be successfully introduced/maintained to facilitate late CNI withdrawal and improve renal function in the setting of graft deterioration, albeit with an increased risk of acute rejection and infection. Additional benefits may include improved blood pressure, lipid profile and serum glucose.Sirolimus has less data directly comparing CNI withdrawal to an active CNI-containing regimen, but modest improvement in short-term renal function is possible, with an increased risk of proteinuKidney transplantation improves quality of life and reduces the risk of mortality. A majority of the success of kidney transplantation is attributable to the calcineurin inhibitors(CNIs), cyclosporine and tacrolimus, and their ability to reduce acute rejection rates. However, longterm graft survival rates have not improved over time, and although controversial, evidence does suggest a role of chronic CNI toxicity in this failure to improve outcomes. Consequently, there is interest in reducing or removing CNIs from immunosuppressive regimens in an attempt to improve outcomes. Several strategies exist to spare calcineurin inhibitors, including use of agents such as mycophenolate mofetil(MMF), mycophenolate sodium(MPS), sirolimus, everolimus or belatacept to facilitate late calcineurin inhibitor withdrawal, beyond 6 mo post-transplant; or using these agents to plan early withdrawal within 6 mo; or to avoid the CNIs all together using CNI-free regimens. Although numerous reviews have been written on this topic, practice varies significantly between centers. This review organizes thedata based on patient characteristics(i.e., the baseline immunosuppressive regimen) as a means to aid the practicing clinician in caring for their patients, by matching up their situation with the relevant literature. The current review, the first in a series of two, examines the potential of immunosuppressive agents to facilitate late CNI withdrawal beyond 6 mo post-transplant, and has demonstrated that the strongest evidence resides with MMF/MPS. MMF or MPS can be successfully introduced/maintained to facilitate late CNI withdrawal and improve renal function in the setting of graft deterioration, albeit with an increased risk of acute rejection and infection. Additional benefits may include improved blood pressure, lipid profile and serum glucose.Sirolimus has less data directly comparing CNI withdrawal to an active CNI-containing regimen, but modest improvement in short-term renal function is possible, with an increased risk of proteinu

关 键 词：Kidney transplantation CALCINEURIN inhibitor WITHDRAWAL Sparing CYCLOSPORINE TACROLIMUS Renal function GRAFT survival 

分 类 号：R[医药卫生]