心脏同种异体移植排斥反应：环孢素谷值水平与组织学排斥反应分级相关吗？

Cardiac allograft rejection: do trough cyclosporine levels correlate with the grade of histologic rejection?

作者信息

el Gamel A, Keevil B, Rahman A, Campbell C, Deiraniya A, Yonan N

机构信息

Cardiothoracic Transplant Unit, Wythenshawe Hospital, Manchester, United Kingdom.

出版信息

J Heart Lung Transplant. 1997 Mar;16(3):268-74.

PMID:9087869

Abstract

BACKGROUND

The introduction of cyclosporine to heart transplantation immunosuppressive protocols has been associated with an improvement in the long- and short-term survival rates. The ideal dose of cyclosporine that maximizes its immunosuppressive properties and minimizes its toxicity has remained an enigma since its introduction. This study was undertaken to evaluate which range of cyclosporine levels provided the most effective protection against graft rejection.

METHODS

We studied the correlation between cyclosporine levels and histologic grade of rejection, cardiac function, and renal function by retrospectively analyzing the results of 1407 individual whole blood cyclosporine trough levels. One hundred seven heart transplant recipients were studied within 2 years of undergoing transplantation. As a historical comparison, we also studied 146 individual trough cyclosporine levels from a subgroup of patients (n = 14) who had acute cellular rejection with graft dysfunction or failure. We correlated trough cyclosporine levels with the histologic severity of cellular rejection, cardiac function (right cardiac catheterization), and serum creatinine in both groups. The correlation was performed within patient's own data rather than between patient groups to avoid interpatient variations.

RESULTS

The mean cyclosporine level was significantly higher (206 ng/ml) when the patients had grade 0 cellular rejection in comparison to grade 3A, with a mean cyclosporine level of 173 ng/ml (p = 0.005). Patients with graft dysfunction or failure had higher mean cyclosporine level (230 ng/ml) when they had no rejection compared with 3A rejection with a mean cyclosporine level of 153 ng/ml (p = 0.001). Furthermore, lower cyclosporine levels were associated with graft dysfunction. There was no correlation between serum creatinine and cyclosporine levels (r = 0.059, r2 = 0.351%).

CONCLUSION

We conclude that cyclosporine trough levels above 200 ng/ml in the first 2 years after heart transplantation are associated with reduced cellular rejection without deleterious effects on renal function.

摘要

背景

将环孢素引入心脏移植免疫抑制方案与长期和短期生存率的提高相关。自环孢素引入以来，能使其免疫抑制特性最大化且毒性最小化的理想剂量一直是个谜。本研究旨在评估哪个环孢素水平范围能提供最有效的抗移植排斥保护。

方法

我们通过回顾性分析1407例个体全血环孢素谷值水平的结果，研究了环孢素水平与排斥反应的组织学分级、心脏功能和肾功能之间的相关性。107例心脏移植受者在移植后2年内接受了研究。作为历史对照，我们还研究了来自一组有急性细胞排斥伴移植功能障碍或衰竭的患者亚组（n = 14）的146例个体环孢素谷值水平。我们将两组中环孢素谷值水平与细胞排斥的组织学严重程度、心脏功能（右心导管检查）和血清肌酐进行了相关性分析。相关性分析是在患者自身数据内进行的，而非在患者组之间进行，以避免患者间的差异。

结果

与3A级细胞排斥相比，患者为0级细胞排斥时，环孢素平均水平显著更高（206 ng/ml），3A级时环孢素平均水平为173 ng/ml（p = 0.005）。移植功能障碍或衰竭的患者在无排斥反应时的环孢素平均水平（230 ng/ml）高于有3A级排斥反应时，后者环孢素平均水平为153 ng/ml（p = 0.001）。此外，较低的环孢素水平与移植功能障碍相关。血清肌酐与环孢素水平之间无相关性（r = 0.059，r2 = 0.351%）。