Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced Natural Killer Cells Mediated (NK-mediated) Rejection
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Estimated glomerular filtration rate
研究概览
简要总结
Background:
Long-term success of organ transplantation is limited by the inexorable loss of graft function due to rejection. Prevalent dogma defends that allograft rejection is exclusively mediated by the adaptive immune system: T cells are responsible for cellular rejections and B cells producing Donor Specific Antibodies (DSA) are responsible for humoral rejection. Recently, we demonstrated that innate NK cells could be implicated in the generation of chronic vascular rejections lesions by sensing the absence of expression of self Major Histocompatibility Complex (MHC) class I molecules ("missing self") on graft endothelial cells with their Killer cell immunoglobulin-like (KIR) receptors. Using human in vitro and murine in vivo models, we also showed that Mammalian Target Of Rapamycin (mTOR) inhibitors could efficiently prevent this new kind of rejection.
Objective:
The aim of our project is therefore to test in a cohort of kidney transplanted patients the efficiency of mTOR inhibitors to treat this new kind of rejection
Methods:
A cohort of 20 kidney transplant patients with a missing self on their graft responsible for a NK-mediated rejection will be established prospectively. An mTOR inhibitor will be introduced in these patients for 6 months in association with a calcineurin inhibitor and corticosteroids. Graft function, histological lesions and NK activability will be monitored following this modification of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient aged > 18 years
- •Kidney transplanted patient
- •Having microvascular inflammation lesion on his graft biopsy associated to mild chronic lesions
- •In absence of donor specific antibodies
- •In presence of a missing self
排除标准
- •Proteinuria/urinary creatinin > 100 mg/mmol
- •Antecedent of poor tolerance or hypersensibility to everolimus or sirolimus
- •Severe chronic lesions
- •Presence of donor specific antibodies
研究组 & 干预措施
Everolimus
干预措施: Everolimus (Drug)
结局指标
主要结局
Change in Estimated glomerular filtration rate
时间窗: 6 months after start of Everolimus treatment
Glomerular filtration rate will be estimated by Chronic Kidney Disease - Epidemiology CollaborationI (CKD-EP) equation. Outcome evaluation at 6 months after everolimus treatment introduction (at D0) compared to baseline (between 15 and 30 days before D0).
次要结局
- Change in the severity of rejection lesions on allograft biopsy(6 months after start of Everolimus treatment)
- Change in proteinuria(6 months after start of Everolimus treatment)
- Change in NK cell activability(6 months after start of Everolimus treatment)