Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Calcineurin activity measured in whole blood and in isolated T-lymphocytes
研究概览
简要总结
The purpose of this study is to determine whether calcineurin phosphatase in the T-lymphocytes is up-regulated after long-term treatment with tacrolimus, a calcineurin inhibitor.
详细描述
Background:
The immunosuppressive effect of both tacrolimus and cyclosporine is believed to be through inhibition of the enzyme calcineurin phosphatase (CaN) in T-lymphocytes. We have demonstrated, that tacrolimus decreases CaN activity in patients early after renal transplantation. In stable renal transplant patients treated this inhibition was hardly seen in patients treated with tacrolimus, while it was clearly demonstrated in patients treated cyclosporine. One explanation to this finding could be, that calcineurin phosphatase is up-regulated by long-term treatment with tacrolimus. The findings seem to imply, that tacrolimus has mechanisms of immunosuppression apart from inhibiting CaN. This could have implications for side-effects due to CaN inhibition. Among side-effects thought to be due to CaN inhibition is nephrotoxicity. The results may therefore be and indication of tacrolimus being less nephrotoxic compared to cyclosporine in long-term stable renal transplant patients.
Purpose:
The aim of the project is find out if long-term treatment with tacrolimus results in up-regulation of CaN in lymphocytes.
Study plan:
研究设计
- 研究类型
- Observational
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group 1 (early kidney-transplant recipients)
- •Age over 18 years
- •20 consecutively kidney-transplant recipients at Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
- •receiving tacrolimus as part of their immunosuppressive treatment
- •receipt of graft from either deceased or living-related donor
- •written consent to participate
- •Group 2 (stable kidney-transplant recipients)
- •Age over 18 years
- •Stable renal allograft function defined as S-creatinine <200 µmol/l
- •variation in S-creatinine <20% for 6 months prior to inclusion
- •kidney transplantation more than 2 years before inclusion
- •receipt of graft from either deceased or living-related donor
- •written consent to participate
排除标准
- •Group 1 (early kidney-transplant recipients)
- •patients suspected of non-compliance
- •patients receiving medications known to interact with tacrolimus pharmacokinetics
- •patients who on day 8 after transplantation have not reached a trough level for blood tacrolimus concentration above 8 µg/l.
- •Group 2 (stable kidney-transplant recipients)
- •patients suspected of non-compliance
- •patients receiving medications known to interact with tacrolimus pharmacokinetics
结局指标
主要结局
Calcineurin activity measured in whole blood and in isolated T-lymphocytes
时间窗: Trough level and 2 hours postdose
Interferon-gamma production
时间窗: Trough level and 2 hours postdose
Amount of Calcineurin in T-lymphocytes
时间窗: Trough level and 2 hours postdose
Gene expression of calcineurin in T-lymphocytes
时间窗: Trough level and 2 hours postdose
次要结局
- Tacrolimus concentration in whole blood(Trough level and 2 hours postdose)
- Number of T-lymphocytes(Trough level and 2 hours postdose)