Relationship between metabolic rate of tacrolimus and BK virus infection early after renal transplantation
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摘要:
目的 探讨他克莫司（FK506）代谢率与肾移植术后早期BK病毒感染的关系。 方法 选择解放军第309医院全军器官移植研究所接受同种异体肾移植术的80例受体作为研究对象。对纳入研究的80例受体进行细胞色素P450（CYP）3A5基因多态性检测，根据基因检测结果分为快代谢组（CYP3A5*1/*3基因型和CYP3A5*1/*1基因型，38例）和慢代谢组（CYP3A5*3/*3基因型，42例）。分析80例受体的CYP3A5基因型分布情况；比较两组受体FK506代谢率[浓度/剂量比（C/D值）]；比较两组受体术后6个月内BK病毒感染事件[包括BK病毒尿症、BK病毒血症、BK病毒性肾病（BKVN）]的发生率。 结果 80例受体中，CYP3A5*1/*1基因型5例（6%），CYP3A5*1/*3基因型33例（41%），CYP3A5*3/*3基因型42例（53%）。在80例受体的160个等位基因中，CYP3A5*3等位基因占117个，即CYP3A5*3等位基因变异率为73.1%。快代谢组受体术后1、3、6个月的C/D值均低于相应时间的慢代谢组，差异均有统计学意义（均为P < 0.01）。快代谢组和慢代谢组受体BK病毒尿症发生率分别为37%和29%，BK病毒血症发生率分别为18%和2%，BKVN发生率分别为3%和0，快代谢组BK病毒血症的发生率高于慢代谢组，差异有统计学意义（P=0.02），两组受体BK病毒尿症和BKVN发生率比较，差异均无统计学意义（均为P > 0.05）。 结论 根据CYP3A5基因型学检测结果发现FK506代谢率高的肾移植受体，其术后早期BK病毒血症发生风险高。 -
关键词:
- BK病毒 /
- 肾移植 /
- 细胞色素P450（CYP）3A5 /
- 基因多态性 /
- 他克莫司代谢率 /
- BK病毒血症 /
- BK病毒尿症 /
- BK病毒性肾病（BKVN）
Abstract:Objective To investigate the relationship between the metabolic rate of tacrolimus (FK506) and BK virus infection early after renal transplantation. Methods Eighty recipients undergoing allogenic renal transplantation in Institute of Organ Transplantation of the 309th Hospital of Chinese People' s Liberation Army were recruited in this study. The polymorphism of cytochrome P450 (CYP) 3A5 gene was detected in 80 recipients. All patients were divided into fast metabolism group (CYP3A5*1/*3 and CYP3A5*1/*1 genotypes, n=38) and slow metabolism group (CYP3A5*3/*3 genotype, n=42) based on the gene detection results. The distribution of CYP3A5 genotypes in 80 recipients was analyzed. The metabolic rate [concentration/dose ratio (C/D value)] of FK506 was statistically compared between two groups. The incidence of BK virus infection events [BK viruria, BK viremia and BK virus nephropathy(BKVN)] within postoperative 6 months were compared between two groups. Results Among 80 recipients, 5 cases (6%) were detected with CYP3A5*1/*1 genotype, 33 (41%) with CYP3A5*1/*3 genotype, and 42 (53%) with CYP3A5*3/*3 genotype. Among the 160 alleles in 80 recipients, 117 CYP3A5*3 allele were identified, suggesting that the mutation rate of CYP3A5*3 allele was 73.1%. In the fast metabolism group, the C/D values at postoperative 1, 3, and 6 months were significantly lower than those in the slow metabolism group (all P < 0.01). The incidence rates of BK viruria in the fast and slow metabolism groups were 37% and 29%, 18% and 2% for BK viremia, and 3% and 0 for BKVN, respectively. In the fast metabolism group, the incidence of BK virenia was significantly higher than that in the slow metabolism group (P=0.02). The incidence of BK viruria and BKVN did not significantly differ between two groups (both P > 0.05). Conclusions According to the CYP3A5 genotyping outcomes, the recipients with a high metabolic rate of FK506 have a high risk of BK viremia early after renal transplantation. -
表 1 两组受体肾移植术后不同时间FK506代谢率的比较
Table 1. Comparison of metabolic rate of FK506 of recipients between the two groups at different time after renal transplantation [M(R), ng/(mL·mg)]
组别 n 术后FK506 C/D值 1个月 3个月 6个月 快代谢组 38 1.3(0.5～2.8) 1.2(0.7～2.2) 1.0(0.6～3.9) 慢代谢组 42 2.1(0.8～6.7) 2.0(1.0～5.4) 2.1(0.6～7.0) P值 < 0.01 < 0.01 < 0.01 
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表 2 两组受体BK病毒尿症、病毒血症及BKVN发生情况的比较
Table 2. Comparison of incidences of BK viruria, viremia and BKVN in recipients between two groups [n(%)]
组别 n BK病毒感染事件 BK病毒尿症 BK病毒血症 BKVN 快代谢组 38 14（37） 7（18） 1（3） 慢代谢组 42 12（29） 1（2） 0 P值 0.43 0.02 0.48
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