抢先治疗肾移植受者BK病毒感染效果与预后分析

Effects and prognosis of pre-emptive immunosuppression reduction on BK virus infection in renal transplant recipients

目的比较肾移植受者可疑BK病毒相关性肾病（BKVAN）和BKVAN的临床治疗效果和预后，确定抢先治疗的有效性和安全性。方法以中山大学附属第一医院2006--2014年通过移植肾穿刺活检并结合尿沉渣Decoy细胞计数，尿、血标本中BK病毒DNA含量测定确诊的BKVAN49例和可疑BKVAN34例患者为研究对象。对于BKVAN和可疑BKVAN的受者进行减少免疫抑制剂强度的治疗，并定期监测BKV的活动及移植肾功能。比较两组1、3、5年移植肾存活率及差异。结果确诊时BKVAN组受者的尿Decoy细胞，尿、血BKV数量的中位水平明显高于可疑BKVAN组旧〈001）。在调整免疫抑制强度后平均为31．1个月（2．4-1013个月）随访期间，可疑BKVAN组BKV尿症的清除率为82．4％，显著高于BKVAN组（28．3％，P〈0．001）。可疑BKVAN组的BKV血症减少和清除平均时间分别为0．9和1．7个月，显著短于BKVAN组（7和11个月，P〈0．001）。两组间6和12个月的血清肌酐水平比较及6和12个月与调药前血清肌酐差值水平比较，可疑BKVAN组均明显低于BKVAN组伊〈O．05）。调药后观察期间两组中均无急性排斥反应的发生。可疑BKVAN组移植肾3年和5年存活率均为97．1％，显著高于BKVAN组（分别为79．2％和66．4％，P=0．049）。结论抢先治疗高水平BKV复制但病理尚未确诊BKVAN的肾移植受者可使病毒快速清除，从而预防BKVAN，改善移植肾功能及提高长期存活率。

Objective To compare the therapeutic effects and prognosis of presumptive BK virus （BKV） associated nephropathy （BKVAN） and definitive BKVAN in renal transplant recipients, and to define the effectiveness and safety of pre-emptive immunosuppression reduction. Methods Between 2006 and 2014, 49 patients with definitive BKVAN, and 34 individuals with presumptive BKVAN were selected from all the recipients who received renal transplant biopsies using three screening methods for BKV including quantitative polymerase chain reaction （PCR） assay for BKV DNA load in urine and plasma and quantitative assay of urine cytology combined with renal transplant biopsies. The I, 3, and S year-graft survival rates were also be calculated and compared. Results Definitive BKVAN patients had a higher median level of decoy cells, BK viruria, and viremia when compared with the presumptive BKVAN patients at diagnosis （all P 〈 0.01）. During the 31.1 （2.4-101.3） months of follow-up after reduction of maintenance immunosuppressionj the frequency of BK viruria clearance was higher in the presumptive BKVAN group （82.4%） than that in the definitive BKVAN group （28.3 %, P 〈 0.001 ）. Presumptive BKVAN, compared with definitive BKVAN, was associated with more rapid viral reduction and clearance time （0.9 vs 7.0 months, 1.7 vs 11.0 months, P 〈 0.001）. The Scr of 6, 12 months post reduction of immunosuppression and the difference between the two time points and time of diagnosis were lower in the presumptive BKVAN patients than those in the definitive BKVAN patients （all P 〈0.05）. No acute rejection was observed during the follow-up post reduction of immunosuppression. The 3- and S-year graft survival rates in the presumptive BKVAN patients were both 97.1%, higher than those in the definitive BKVAN patients （79.2% and 66.4%, P = 0.049）. Conclusions BKV can be cleared in a short-term time using pre- emptive immunosuppression reduction in presumptive BKVAN patients with a high level of BKV replication. This therapy of pre- emptive immunosuppression reduction can improve the graft function and increase the long-term graft survival rate.