Chen Li-zhong, Huang Gang, Qiu Jiang, Li Jun, Chen Guo-dong, Zeng Wen-tao, Fu Qian, Zhang Lei, Ji Yu-lian
Department of Organ Transplantation, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhonghua Yi Xue Za Zhi. 2008 Jul 8;88(26):1824-8.
To explore methods of clinical diagnosis and treatment of BK virus (BKV) infection in renal transplant recipients.
Urine samples were collected from 227 renal transplant recipients who had undergone renal transplantation at most 48 months to detect the decoy cells. Samples of urine and peripheral blood (BP) were collected to undergo real-time PCR to detect the BKV DNA. Part of the renal-recipients received graft biopsy. The recipients with BKV viruria or viremia were divided into 2 groups: intervention group and control group. The 51 patients of the intervention group had the doses of cyclosporine A (CsA) reduced (n=19), had their doses of FK506 reduced (n=22), or underwent replacement of FK506 with CsA (n=10). And other 29 patients in the control group did not receive any intervention. Acute rejection was intensively monitored. The amount of decoy cells, and BKV load in the urine and PB samples were measured again after 3 months.
The positive rates of urine decoy cell, BKV viruria, and viremia in all patients were 33.0%, 33.5%, and 15.4% respectively. In the intervention group, the median levels of decoy cells in urine, and of BKV DNA in urine and PB before intervention were 5.0/10 HP, 1.50 x 10(4) copies/ml and 0 copy/ml respectively ; and the median levels of decoy cell in urine, and of BKV DNA in urine and PB were all 0 after intervention, all significantly lower than those before intervention (all P < 0.01). In the control group, the median levels of decoy cells in urine, and of BKV DNA in urine and PB were 6.0 /10 HP, 0.79 x 10(4) copies/ml, and 0 copy/ml respectively before observation, and the median level of BKV load in urine ofter observation was 2.21 x 10(4) copies/m, significantly higher than that before observation (P < 0.01), however, the median levels of decoy cells in urine and of BKV DNA in PB were 5.0 /10 HP and 0 copy/ml respectively, not significantly different from those before observation ( both P > 0.05). The differences between the levels of urine decoy cells, urine BKV DNA level and blood BKV DNA level of the intervention group were all significantly greater than those of the control group (Z = -2.749, -5.089, -1.996; P = 0.006, 0.000, 0.046 respectively). And during the intervention no acute rejection was observed. Four cases of BKVAN were diagnosed. Treatment of immunosuppression reduction showed effectiveness in 4 BKVAN recipients. The levels of decoy cells in urine, and BKV load in urine and in PB samples were all decreased. The graft functions were improved.
Urine cytology is very convenient, useful and sensitive for the evaluation and followup of renal transplant patients, and can reflect renal histological presentation indirectly. Also BKV DNA detection in the urine and peripheral blood is important to screen the evidence of BK reaction in order to prevent irreversible graft damage of BKVAN. The treatment of immunosuppressant reduction and replacement of FK506 with CsA are effective in BKV infection recipients at the early stage.
探讨肾移植受者BK病毒(BKV)感染的临床诊断和治疗方法。
收集227例肾移植时间最长48个月的肾移植受者的尿液样本以检测诱饵细胞。收集尿液和外周血样本进行实时聚合酶链反应(PCR)以检测BKV DNA。部分肾移植受者接受移植肾活检。将出现BKV病毒尿或病毒血症的受者分为2组:干预组和对照组。干预组的51例患者减少了环孢素A(CsA)剂量(n = 19),减少了他克莫司(FK506)剂量(n = 22),或用CsA替代FK506(n = 10)。对照组的其他29例患者未接受任何干预。密切监测急性排斥反应。3个月后再次测量尿液中的诱饵细胞数量以及尿液和外周血样本中的BKV载量。
所有患者尿液诱饵细胞、BKV病毒尿和病毒血症的阳性率分别为33.0%、33.5%和15.4%。干预组干预前尿液中诱饵细胞的中位数水平以及尿液和外周血中BKV DNA的中位数水平分别为5.0/10高倍视野(HP)、1.50×10⁴拷贝/毫升和0拷贝/毫升;干预后尿液中诱饵细胞的中位数水平以及尿液和外周血中BKV DNA的中位数水平均为0,均显著低于干预前(均P < 0.01)。对照组观察前尿液中诱饵细胞的中位数水平以及尿液和外周血中BKV DNA的中位数水平分别为6.0/10 HP、0.79×10⁴拷贝/毫升和0拷贝/毫升,观察后尿液中BKV载量的中位数水平为2.21×10⁴拷贝/毫升,显著高于观察前(P < 0.01),然而,尿液中诱饵细胞的中位数水平以及外周血中BKV DNA的中位数水平分别为5.0/10 HP和0拷贝/毫升,与观察前无显著差异(均P > 0.05)。干预组尿液诱饵细胞水平、尿液BKV DNA水平和血液BKV DNA水平与对照组的差异均显著大于对照组(Z = -2.749、-5.089、-1.996;P分别为0.006、0.000、0.046)。并且在干预期间未观察到急性排斥反应。诊断出4例BKV相关性肾病(BKVAN)。免疫抑制减少治疗对4例BKVAN受者显示有效。尿液中的诱饵细胞水平以及尿液和外周血样本中的BKV载量均降低。移植肾功能得到改善。
尿液细胞学检查对于肾移植患者的评估和随访非常方便、有用且敏感,并且可以间接反映肾脏组织学表现。此外,检测尿液和外周血中的BKV DNA对于筛查BK反应的证据很重要,以防止BKVAN导致不可逆转的移植肾损害。减少免疫抑制剂治疗以及用CsA替代FK506对早期BKV感染受者有效。