肾移植受者BK病毒尿症的长期预后分析

Analysis of BK viruria on the long term graft survival in renal transplant recipients

目的 探讨按预先制定的方案对BK病毒（BKV）感染的肾移植受者进行干预后,观察BKV尿症的清除情况及其对移植肾长期存活率和肾功能的影响.方法 回顾性分析2006年3月至2008年10月中山大学附属第一医院进行肾移植的229例患者的资料,所有患者均在移植后第1、3、6、9、12个月收集尿标本,进行尿沉渣Decoy细胞计数与BKV DNA含量的检测.应用免疫组织化学方法检测移植肾组织中的SV40-T抗原.按预先制定的方案对BKV感染肾移植患者调整免疫抑制剂的用量,随访观察移植肾功能及BKV的活动情况,所有患者随访5年以上.结果 229例肾移植受者随访1年内,尿液Decoy细胞阳性78例,尿BKV DNA阳性（BKV尿症）99例,其中移植肾病理检出BK病毒相关性肾病（BKVAN）7例.中位随访时间为63.6（3.0 ～88.0）个月.调整免疫抑制剂后,99例BKV尿症患者中81例（81.8％）尿BKV转阴,所需的平均时间为（12.1±1.9）个月.BKVAN患者尿BKV峰值水平明显高于无BKVAN的BKV尿症患者（中位数：2.07×109比9.28×105拷贝/ml,P =0.002）,尿BKV清除率明显低于无BKVAN的BKV尿症患者（3/7比78/92,P=0.006）,尿BKV清除所用时间明显长于无BKVAN的BKV尿症患者[（45.4±6.4）比（8.7±1.5）个月,P=0.001].BKV尿症患者移植肾1、3和5年存活率（99.0％、95.9％、89.6％）及第5年移植肾功能[血清肌酐（105.7 ±30.9） μmol/L],与无BKV尿症患者[97.7％、95.5％、93.7％、（111.3 ±44.6） μmol/L]比较差异无统计学意义（均P＞0.05）.BKVAN患者随访5年移植肾功能稳定,且与无BKVAN的BKV尿症患者比较差异无统计学意义[血清肌酐：（127.6±41.0）比（108.3±39.3）μmol/L,P=0.204].结论 规律监测BKV活动并按预先制定的方案调整免疫抑制剂用量的前提下,BKV尿症及BKVAN并不影响移植肾的长期存活。

Objective To observe the clearance of BK viruria and long-term graftsurvival in renal transplant recipients with BK virus （BKV） infection under the protocol of our center.Methods Urine was taken from 229 renal transplant recipients,who were transplanted between March 2006 to October 2008,for BKV cytological testing and real-time PCR for BKV DNA at 1,3,6,9,and 12 months after transplantation.Graft biopsies were analyzed for SV40-T by immunohistochemical method.Recipients were treated according to the BKV infection protocol of our center and were monitored for BKV and graft function.All the patients were followed for at least 5 years.Results By 1 year post-transplant,urinary decoy cells,BK viruria,and BKV associated nephropathy （BKVAN） occurred in 78,99,and 7 patients,respectively.The median followed-up time was 63.6 （3.0-88.0） months.After reduction of immunosuppression,81 （81.8%） patients cleared BK viruria with a mean time of （12.1 ± 1.9） months.When compared with non-BKVAN patients,BKVAN patients had a higher median peak level of BK viruria （2.07 × 109 vs 9.28 × 105copies/ml,P =0.002）,lower frequency of clearance （3/7 vs 78/92,P =0.006）,longer BK viruria clearance time （（45.4 ±6.4） vs （8.7 ± 1.5） months,P =0.001）.The 1,3,5-yeargraft survival in BK viruria patients were 99.0%,95.9% and 89.6% respectively,which were not significantly different from those in non-BK viruria patients（97.7%,95.5% and 93.7%,P =0.289）.Graft function of BK viruria patients were not statistical significance compared with non-BK viruria patients （serum creatinine level 5 years posttransplant：（105.7 ± 30.9） vs （111.3 ± 44.6） μmol/L,P =0.322）.Graft function of BKVAN patients at 5 years post-transplantwas stable without significantly difference from non-BKVAN patients （serum creatinine level：（127.6 ± 41.0）vs （108.3 ± 39.3） μmol/L,P =0.204）.Conclusion On the premise of intensively and regularly BKV monitoring and preemptive reduction of immunosuppression,BK viruria and BKVAN can not impact on the long-term graft survival in renal transplant recipients.