肾移植受者BK病毒感染的临床诊断及治疗

目的 探讨肾移植受者BK病毒(BKV)感染的诊断及治疗方法.方法 选取肾移植术后48个月内的患者共227例.采集其血、尿样本,行BKV尿沉渣细胞学计数与实时荧光定量PCR检测病毒拷贝.对部分肾移植受者进行移植肾活检.将尿或血中BKV DNA阳性患者80例分成干预组(51例)与对照组(29例).干预组进行调整免疫抑制剂:19例环孢素A(CsA)减量,22例他克莫司(FK506)减量,10例FK506转换成CsA;对照组不进行干预,并且密切监测急性排斥反应.干预3个月后再次检测,比较组内和组间干预前后BKV活化指标的差异.结果 227例受者的尿decoy细胞、BK病毒尿症与病毒血症的阳性率分别为33.O%、33.5%和15.4%.干预组干预后尿decoy细胞、尿和血BKV数量的中位水平均为O,明显低于干预前(5.0个/10HP,1.50 x 104拷贝/ml,0拷贝/ml,均P<0.01).对照组观察前后尿decoy细胞、血BKV数量的中位水平差异无统计学意义(6.0个/10HPvs 5.0个/10HP、0拷贝/ml vs 0拷贝/ml,均P>0.05),尿BKV数量观察结束时上升(观察前:0.79×104拷贝/ml,观察后:2.21 x104拷贝/ml,P<0.01).上述各项指标干预前后的差值在干预组与对照组间差异均有统计学意义(均P<0.05).干预过程中所有患者均未出现急性排斥反应.确诊BKV相关性肾病4例,其干预治疗后尿decoy细胞计数以及血、尿BKV DNA均明显降低,移植肾功能有所恢复.结论 定量尿沉渣细胞学检测简单、易行、敏感,可以作为BKV活化的指标,间接反映肾脏病理情况.也可检测血、尿BKV DNA了解病毒活化情况、筛查BKV相关的移植肾肾病.减少免疫抑制剂剂量或换FKS06为CsA治疗肾移植术后BKV感染效果良好.

Clinical diagnosis and treatment of BK virus infection in renal transplant recipients

Objective To explore metheds of chnical diagnosis and treatment of BK virus(BKV) infection in renal transplant recipients.Methods 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 vrine and peripheral bloed(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 vimria or viremia were divided into 2geroups: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 witIl 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.Results The positive rates of urine decoy cell,BKV viruria.and viremia in all pailents were 33.0%,33.5%,and 15.4%respectively.In the intervention group.the median hveh of decoy cells in urine,and of BKV DNA in urine and PB before intervention were 5.0/10 HP.1.50 x 104copies/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 significanfly lower than those before intervention(all P<0.01).In the control group,the median levels of decoy ceils in urine.and of BKV DNA in urine and PB were 6.0/10 HP,0.79×104 copiesd/ml,and 0 copy/ml respectively before observation,and the median level of BKV load in urine ofter obsevation was 2.21 x 104copies/ml,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 significantlly 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.Conclusion Urilie cytology is very convenient,useful and sensitive for the evaluation and followup ofrenal transplant patients,and can reflect renal histological presentation indirect]y.Also BKV DNAdetection 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.