Clinical Application of Mammalian Target of Rapamycin Inhibitor in Kidney Transplantation.
- Author:
Myoung Soo KIM
1
;
Soon Il KIM
;
Yu Seun KIM
Author Information
1. Department of Surgery and The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea. ysms91@yumc.yonsei.ac.kr
- Publication Type:Clinical Trial ; Review
- Keywords:
Mammalian target of rapamycin inhibitor;
Proliferation signal inhibitor;
Kidney transplantation
- MeSH:
Antimetabolites;
Calcineurin;
Cell Cycle;
Everolimus;
Graft Survival;
Half-Life;
Kidney;
Kidney Transplantation;
Korea;
Proteinuria;
Rejection (Psychology);
S Phase;
Sarcoma, Kaposi;
Sirolimus;
Skin Neoplasms;
Transplantation, Homologous;
Transplants;
Wound Healing
- From:The Journal of the Korean Society for Transplantation
2008;22(2):169-176
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Mammalian target of rapamycin inhibitors (mTOR-I)* is a novel immunosuppressive agent that has the variable action mode, such as anti-fibroblastic, anti-tumor and anti-atherosclerotic effect, but doesn't have a nephrotoxicity. Since March 2006, two types of mTOR-I, sirolimus and everolimus, are clinically available in Korea. In this article, we summarize the pharmacologic characteristics of mTOR-I and review the clinical application of mTOR-I as the component of immunosuppressive regimen after kidney transplantation. Sirolimus and everolimus share the same action mode resulting in an arrest of cell cycle (G1 to S phase arrest). Despite the similarities of chemical structure between sirolimus and everolimus, there are remarkable pharmacokinetic differences between the two molecules. In summary, the half-life and time to reach steady state of everolimus is shorter than those of sirolimus. Therefore, there are significant difference in administration interval and mode. Four types of clinical application of mTOR-I were tried in de Novo renal transplant recipients; (1) for replacement of calcineurin inhibitor (CNI), (2) for replacement of antimetabolites, (3) in combination CNI with low dose mTOR-I versus high dose mTOR-I, (4) standard dose CNI plus low dose mTOR-I versus low dose CNI plus high dose mTOR-I. Generally, mTOR-I shows superior results in graft survival rate, acute rejection free rate and graft renal function (eGFR), but shows inferior results in maintenance rate of regimen and occurrence of side effect (such as proteinuria, wound healing problem and dyslipidemia). Conversion from CNI to mTOR-I was tried in recipients with de Novo post- transplant malignancy or chronic allograft dysfunction. These clinical trial data suggest that mTOR-I may be useful in management of selective type of post-transplant malignancy (such as non-melanoma skin cancer, Kaposi's sarcoma and post- transplant lymphoproliferative disease) or chronic allograft dysfunction with CNI nephrotoxicity. Clinical application of mTOR-I makes variable combination of immunosuppressive agent possible. Therefore, it is possible to make the selective or tailored immunosuppressive regimen that yields the best outcome with minimal adverse effect.
