BK病毒血症对肾移植术后受者和移植肾功能影响临床研究

目的探究肾移植术后BK病毒(BKV)血症对受者及移植肾功能的影响。 方法回顾性分析2014年1月至2018年1月于中国科学技术大学附属第一医院接受肾移植229例受者临床资料。根据移植术后24个月内受者血清BKV最大载量，将其分为无病毒组(血清BKV持续阴性)、低病毒载量组(血清BKV最大载量≤1×10⁴ copies/mL)和高病毒载量组(血清BKV最大载量>1×10⁴ copies/mL)。以估算肾小球滤过率(eGFR)作为评价移植肾功能的指标。观察受者年龄和性别、供肾来源、供肾冷/热缺血时间、免疫抑制方案、术后3个月他克莫司血药浓度谷值、排斥反应和移植肾失功发生率以及术后24个月内eGFR。采用单因素方差分析比较3组受者年龄、供肾冷/热缺血时间、术后3个月他克莫司血药浓度谷值及术后24个月内eGFR，组间两两比较采用LSD法。采用成组t检验比较低病毒载量组与高病毒载量组受者首次检测到BKV的术后时间。采用卡方检验比较3组受者供肾来源、免疫抑制方案以及排斥反应和移植肾失功发生率。P<0.05为差异有统计学意义。 结果229例受者中28%(64/229)的受者肾移植术后血清检测到BKV，其中19%(43/229)为低病毒载量，9%(21/229)为高病毒载量。截至2018年7月，229例受者平均随访时间(44±8)个月。低病毒载量组受者术后首次检测到BKV的时间为移植后(10±8)个月，高病毒载量组为(8±6)个月，差异有统计学意义(t＝2.10，P<0.05)。无病毒组受者排斥反应发生率[24.8%(41/165)]低于低病毒载量组[60.5%(26/43)]和高病毒载量组[61.9%(13/21)](χ²＝19.82和12.42，P均<0.017)。无病毒组受者细胞排斥反应发生率[13.9%(23/165)]低于低病毒载量组[39.5%(17/43)]和高病毒载量组[42.9%(9/21)](χ²＝14.38和10.94，P均<0.017)。无病毒组受者中12例发生移植肾失功，低病毒载量组受者中2例发生移植肾失功，高病毒载量组受者中4例(3例发生BKVAN，1例病因不明确)发生移植肾失功，差异无统计学意义(χ²＝4.727，P>0.05)。高病毒载量组受者术后第3个月他克莫司血药浓度谷值高于无病毒组和低病毒载量组(P均<0.05)。高病毒载量组受者术后第3、6、12、24个月eGFR均低于无病毒组和低病毒载量组(P均<0.05)。 结论肾移植术后高BKV血症会影响肾移植受者预后及移植肾功能；而低BKV血症对移植肾功能无明显不良影响，此类受者无需调整他克莫司剂量。

Clinical study on the influence of BK virus viremia on the recipient and the function of transplant kidney after transplantation

ObjectiveTo explore the effect of BK virus viremia on the recipient and the function of transplant kidney after transplantation. MethodsThe clinical data of 229 recipients who received kidney transplantation in the First Affiliated Hospital of University of Chinese Academy of Sciences were analyzed retrospectively. According to the maximum serum BK virus load within 24 months after transplantation, the recipients were divided into virus-free group (serum BKV continued negative), low virus load group (serum BKV maximum load≤1×10⁴ copies/mL) and high virus load group (serum BKV maximum load>1×10⁴ copies/mL). The estimated glomerular filtration rate (eGFR) was used to evaluate the kidney function. The age and gender of the recipients, the source of the donor kidney, the time of cold/hot ischemia of the donor kidney, the immunosuppressive program, the blood trough concentration of tacrolimus at 3 months after transplantation, the incidence of rejection and graft dysfunction, and the eGFR within 24 months after transplantation was observed. Single factor analysis of variance was used to compare the age of recipients, the time of cold/hot ischemia of donor kidney, the blood trough concentration of tacrolimus at 3 months after transplantation and eGFR in 24 months after transplantation in the 3 groups and that between groups with LSD method. Group t test was used to compare the first detection time of BK virus infection between the low virus load group and the high virus load group. Chi square test was used to compare the source of donor kidney, immunosuppressive regimen, and the incidence of graft failure and rejection. P<0.05 was statistically significant. ResultsBK virus viremia was detected in 64 recipients among 229 recipients (28%), of which 19% (43/229) was low virus load and 9% (21/229) was high virus load. As of July 2018, the average follow-up time of 229 recipients was (44±8) months. The first detection time of BK virus infection was (10±8) months after transplantation in low virus load group and (8±6) months in high virus load group, which had statistical significance (t=2.10, P<0.05). The rejection rate of virus-free group [24.8% (41/165)] was lower than that of low virus load group [60.5% (26/43)] and high virus load group [61.9% (13/21)] (χ²=19.82 and 12.42, P all<0.017). The incidence of cellular rejection in virus-free group [13.9% (23/165)] was lower than that in low virus load group [39.5% (17/43)] and high virus load group [42.9% (9/21)] (χ²=14.38 and 10.94, P<0.017). 12 recipients in the virus-free group, 2 recipients in the low virus load group, 4 recipients in the high virus load group (3 with BK virus associated nephropathy, 1 with unclear etiology) had renal allograft dysfunction, which had no statistical significance (χ²=4.727, P>0.05). The blood trough concentration of tacrolimus at 3 months after transplantation in the high viral load group was higher than that in the virus-free group and the low virus load group (P all<0.05). At the 3th, 6th, 12th and 24th month after operation, eGFR of the recipients in the high virrus load group were all lower than that in the virus-free group and the low virus load group (P all<0.05). ConclusionsHigh BK virus viremia after kidney transplantation can significantly affect the prognosis of recipients; low BK virus viremia had no significant adverse effect on the function of transplant kidney, and there was no need to adjust the dosage of tacrolimus for recipients with low BK virus viremia.