Cyclosporine lymphocyte versus whole blood pharmacokinetic monitoring: Correlation with histological findings
Cyclosporine lymphocyte versus whole blood pharmacokinetic monitoring: Correlation with histological findings
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DOI：
10.1016/s0041-1345(01)02190-x
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发表时间：
2001-08-01
影响因子：
0.9
通讯作者：
Joubran, N
中科院分区：
文献类型：
--
作者：
Barbari, A;Masri, MA;Joubran, N
材料与方法本研究纳入46例移植物功能障碍患者（平均血清肌酐Scr为2.2 mg/dL）。35例患者接受了43次移植物活检，其余11例患者有孤立的巨细胞病毒疾病。选取26例移植后病程平稳、移植物功能正常（平均Scr 1.2 mg/dL）的历史对照组进行比较。所有组均采用以氰胺为基础的三联疗法，并根据年龄、性别、体重、供体年龄和类型进行匹配。接受移植物活检的患者（35例）分为A组：CyA毒性；B组：急性排斥反应；C组：巨细胞病毒相关急性排斥反应。将移植物功能正常的对照组患者分为d组。20例患者在移植后一年内进行移植物活检，其余15例患者在移植后一年后进行肾脏活检。移植物功能障碍被定义为在没有超声异常的情况下Scr持续波动和/或Scr持续上升（比基线高30%）。如果在CMV-PCR阳性患者开始Cymevan治疗或CMV-PCR阴性患者CyA剂量逐渐减少后，肾功能没有改善或持续恶化，则进行移植物活检。根据先前描述的标准诊断急性和慢性CyA毒性。正常活检结果在不明原因的移植物功能障碍背景下被认为是急性CyA肾毒性。根据Banff标准诊断急性排斥反应。16在活检时，除了CBC和总Lc计数外，还获得了以下CyA药代动力学参数BTL和LTL。采用单克隆抗体（Abbott TDx法）测定全血CyA/BTL。CyA LTL以picog/Lc表示，根据Masri等人的方法测定。7结果以均数SD表示，采用Student’s t检验和卡方检验进行比较。p < 0.05认为差异有统计学意义。
MATERIALS AND METHODSForty-six patients with graft dysfunction (mean serum creatinine Scr of 2.2 mg/dL) were included in this study. Thirty-five underwent 43 graft biopsies, and the remaining eleven patients had isolated CMV disease. A historical control group of 26 patients with uneventful posttransplant course and normal graft function (mean Scr 1.2 mg/dL) was chosen for comparison. All groups were on CyA-based triple therapy and were matched for age, gender, weight, and donor age and type. Patients who underwent graft biopsies (35) were divided into Group A: CyA toxicity; Group B: Acute rejection; and Group C: CMV-associated acute rejection. Control patients with normal graft function were assigned to Group D. Twenty patients had their graft biopsies within the first year posttransplantation, and the remaining 15 underwent kidney biopsies after the first year following transplantation. Graft dysfunction was defined as persistent ffuctuation in Scr and/or continuous rise in Scr (30% from baseline) in the absence of ultrasonographic abnormalities. The graft biopsy was performed if no improvement or continuous deterioration in renal function were noted despite the initiation of Cymevan therapy in CMV-PCR positive patients or the tapering of CyA dose in CMV-PCR negative patients. Acute and chronic CyA toxicity were diagnosed according to previously described criteria. 15 Normal biopsy findings in the context of an unexplained graft dysfunction was presumed to be acute CyA nephrotoxicity. Acute rejection was diagnosed according to the Banff criteria. 16 At the time of the biopsy, the following CyA pharmacokinetic parameters BTL and LTL were obtained in addition to a CBC and total Lc count. CyA/BTL was measured in whole blood using monoclonal antibodies (Abbott TDx method). The CyA LTL expressed in picog/Lc, was determined according to the method of Masri et al. 7 Results were expressed as mean SD and were compared using the Student’s t test and chi-square test. Differences were considered to be statistically significant for P. 05.