切换至 "中华医学电子期刊资源库"
高级检索
中华移植杂志(电子版)

中华移植杂志(电子版) ›› 2021, Vol. 15 ›› Issue (04) : 211 -215. doi: 10.3877/cma.j.issn.1674-3903.2021.04.004

论著

肾移植术后主动监测对BK病毒相关性肾病治疗预后的影响
刘德川1, 周洪澜1, 王金国1, 刘俊彦1, 朱亚香1, 于迪1, 王钢1,†()   
  1. 1. 130000　长春，吉林大学第一医院泌尿外二科
  • 收稿日期:2021-03-03 出版日期:2021-08-25
  • 通信作者: 王钢

Effect of active monitoring of BK virus on prognosis of BK virus nephropathy after renal transplantation

Dechuan Liu1, Honglan Zhou1, Jinguo Wang1, Junyan Liu1, Yaxiang Zhu1, Di Yu1, Gang Wang1,†()   

  1. 1. The Second Department of Urology, the First Hospital of Jilin University, Changchun 130000, China
  • Received:2021-03-03 Published:2021-08-25
  • Corresponding author: Gang Wang
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

刘德川, 周洪澜, 王金国, 刘俊彦, 朱亚香, 于迪, 王钢. 肾移植术后主动监测对BK病毒相关性肾病治疗预后的影响[J]. 中华移植杂志(电子版), 2021, 15(04): 211-215.

Dechuan Liu, Honglan Zhou, Jinguo Wang, Junyan Liu, Yaxiang Zhu, Di Yu, Gang Wang. Effect of active monitoring of BK virus on prognosis of BK virus nephropathy after renal transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(04): 211-215.

目的

探讨肾移植术后主动规律监测BK病毒(BKV)对BK病毒相关性肾病(BKVN)预后的临床意义。

方法

选取吉林大学第一医院2015至2018年接受同种异体肾移植术后经病理证实为BKVN的36例受者为研究对象，根据其BKV监测情况分为主动监测组(15例)和被动发现组(21例)，观察两组BKV尿症和血症检出时间、BKV DNA载量、BKVN确诊时间，以及治疗后血清和尿液BKV转阴情况和移植肾功能等指标。

结果

主动监测组受者BKV尿症检出时间为术后(5.3±3.4)个月，BKV血症检出时间为术后(7.8±3.8)个月，BKVN确诊时间为术后(10.3±7.4)个月，均早于被动发现组[(12.6±2.7)、(15.3±13.6)和(19.9±10.2)个月]，差异均有统计学意义(t＝0.024、0.013和0.027，P均<0.05)。经治疗后主动监测组和被动发现组血清BKV转阴(14/15和11/21)和尿液BKV转阴(12/15和10/21)的受者比例差异均有统计学意义(χ2＝0.029和0.012，P均<0.05)。同时，主动监测组尿液BKV转阴时间为治疗后(3.3±3.2)个月，血清BKV转阴时间为治疗后(0.8±0.7)个月，均早于被动发现组[(5.6±2.1)和(3.6±2.1)个月]，差异均有统计学意义(t＝0.041和0.027，P均<0.05)。主动监测组发生移植肾失功/功能不全的受者比例(4/15)低于被动发现组(13/21)，差异有统计学意义(χ2＝0.015，P<0.05)。

结论

肾移植术后主动、规律开展BKV监测，有助于尽早确诊BKVN、提高BKV转阴比例和缩短BKV转阴时间，以及减少移植肾失功的发生。

关键词: 肾移植, BK病毒血症, BK病毒尿症, BK病毒相关性肾病, 移植肾活检
Objective

To investigate the clinical significance of regular monitoring of BK virus (BKV) infection on the prognosis of BK virus nephropathy (BKVN) after renal transplantation.

Methods

Thirty-six renal transplant recipients with pathologically confirmed BKVN from 2015 to 2018 in our center were selected as the research objects. According to their BKV monitoring, the recipients were divided into active monitoring group (15 cases) and passive discovery group (21 cases). The detection time of BKV urination and blood, BKVDNA load, time to diagnosis of BKVN, serum and urine BKV conversion after treatment and renal allograft function were observed in the two groups.

Results

The detection time of BKV, BKV and BKVN was (5.3±3.4) months, (7.8±3.8) months and (10.3±7.4) months, respectively. There were significant differences in the proportion of recipients with serum BKV conversion (14/15 and 11/21) and urine BKV conversion (12/15 and 10/21) in the passive monitoring group after treatment (χ2=0.029 and 0.012, P<0.05). The time of urine BKV conversion in the subjective monitoring group was (3.3±3.2) months after treatment, and the time of serum BKV conversion was (0.8±0.7) months after treatment, which were earlier than those in the passive discovery group [(5.6±2.1) months and (3.6±2.1) months], and the differences were statistically significant (t=0.041 and 0.027, all P<0.05). The proportion of recipients who developed renal allograft failure/insufficiency was lower in the active monitoring group (4/15) than in the passive discovery group (13/21), and the difference was statistically significant (χ2=0.015, P<0.05).

Conclusions

Active and regular monitoring of BKV after renal transplantation is helpful for early diagnosis of BKVN, increasing the proportion of BKV conversion, shortening the time of BKV conversion and reducing the occurence of renal allograft failure.

Key words: Renal transplantation, BK viremia, BK virouria, BK virus nephropathy, Renal graft biopsy
表1 两组肾移植术后BKVN受者一般情况和BKV感染相关危险因素比较
组别 例数 性别(例，男/女) 年龄(岁，±s) 免疫诱导方案(例，ATG/巴利昔单抗) CNI方案(例，他克莫司/环孢素) 热缺血时间(min，±s) 冷缺血时间(h，±s) HLA抗原错配数(个，±s) DGF(例)
被动发现组 21 13/8 46±12 16/5 11/10 4.1±1.3 5.6±3.2 1.8±0.7 3
主动监测组 15 9/6 43±11 12/3 9/ 6 4.1±1.7 5.7±4.2 2.0±0.8 2
χ2/t值 - 0.278 0.129 - 0.382 0.122 0.324 0.421 -
P值 - >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
表2 两组肾移植术后BKVN受者BKV感染相关临床指标比较(±s)
组别 例数 BKV尿症检出时间(月) 尿液BKV DNA载量(copies/mL) BKV血症检出时间(月) 血清BKV DNA载量(copies/mL) BKVN确诊时间(月)
峰值 均值 峰值 均值
被动发现组 21 12.6±2.7 (2.23±1.23)×1010 (1.74±0.86)×109 15.3±13.6 (1.13±0.63)×105 (1.67±0.52)×104 19.9±10.2
主动监测组 15 5.3±3.4 (1.41±1.09)×1010 (2.38±0.92)×109 7.8± 3.8 (5.51±2.12)×105 (6.26±1.89)×103 10.3± 7.4
t值 - 0.024 0.396 0.619 0.013 0.641 0.545 0.027
P值 - <0.05 >0.05 >0.05 <0.05 >0.05 >0.05 <0.05
1
Sellarés J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: The dominant role of antibody-mediated rejection and non-adherence[J]. Am J Transplant, 2012, 12(2): 388-399.
2
Kean JM, Rao S, Wang M, et al. Seroepidemiology of human polyomaviruses[J]. PLoS Pathog, 2009, 5(3): e1000363.
3
Garces JC. BK virus-associated nephropathy in kidney transplant recipients[J]. Ochsner J, 2010, 10(4): 245-249.
4
Elfadawy N, Flechner SM, Liu X, et al. The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation[J]. Transplant Int, 2013, 26(8): 822-832.
5
Weiss AS, Gralla J, Chan L, et al. Aggressive immunosuppression minimization reduces graft loss following diagnosis of BK virus-associated nephropathy: a comparison of two reduction strategies[J]. Clin J Am Soc Nephrol, 2008, 3(6): 1812-1819.
6
Hardinger KL, Koch MJ, Bohl DJ, et al.BK-virus and the impact of pre-emptive immunosuppression reduction: 5-year results[J]. Am J Transplant, 2010, 10(2): 407-415.
7
Hirsch HH, Vincenti F, Friman S, et al. Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study[J]. Am J Transplant, 2013, 13(1): 136-145.
8
Schaub S, Hirsch HH, Dickenmann M, et al. Reducing immunosuppression preserves allograft function in presumptive and definitive polyomavirus-associated nephropathy[J]. Am J Transplant, 2010, 10(12): 2615-2623.
9
Petrov R, Elbahloul O, Gallichio MH, et al. Monthly screening for polyoma virus eliminates BK nephropathy and preserves renal function[J]. Surg Infect (Larchmt), 2009, 10(1): 85-90.
10
Hodowanec AC, Simon DM. BK virus screening and management practices among US renal transplant programs: a survey[J]. Transpl Int, 2015, 28(11): 1339-1341.
11
Leboeuf C, Wilk S, Achermann R, et al. BK polyomavirus-specific 9mer CD8 T cell responses correlate with clearance of BK viremia in kidney transplant recipients: first report from the Swiss transplant cohort study[J]. Am J Transplant, 2017, 17(10): 2591-2600.
12
Bischof N, Hirsch HH, Wehmeier C, et al. Reducing calcineurin inhibitor first for treating BK polyomavirus replication after kidney transplantation: long-term outcomes[J]. Nephrol Dial Transplant, 2019, 34(7): 1240-1250.
13
Höcker B, Schneble L, Murer L, et al. Epidemiology of and risk factors for BK polyomavirus replication and nephropathy in pediatric renal transplant recipients: an International CERTAIN Registry Study[J]. Transplantation, 2019, 103(6): 1224-1233.
14
Schachtner T, Babel N, Reinke P. Different risk factor profiles distinguish early onset from late onset BKV-replication[J]. Transpl Int, 2015, 28(9): 1081-1091.
15
Imlay H, Whitaker K, Fisher CE, et al. Clinical characteristics and outcomes of late-onset BK virus nephropathy in kidney and kidney-pancreas transplant recipients[J]. Transpl Infect Dis, 2018, 20(4): e12928.
16
Brennan DC, Agha I, Bohl DL, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction[J]. Am J Transplant, 2005, 5(3): 582-594.
17
Schwarz A, Linnenweber-Held S, Heim A, et al. Viral origin, clinical course, and renal outcomes in patients with BK virus infection after living-donor renal transplantation[J]. Transplantation, 2016, 100(4): 844-853.
18
Pang XL, Doucette K, LeBlanc B, et al. Monitoring of polyomavirus BK virus viruria and viremia in renal allograft recipients by use of a quantitative real time PCR assay: one year prospective study[J]. J Clin Microbiol, 2007, 45(11): 3568-3573.
19
Funk GA, Gosert R, Comoli P, et al. Polyomavirus BK replication dynamics in vivo and in silico to predict cytopathology and viral clearance in kidney transplants[J]. Am J Transplant, 2008, 8(11): 2368-2377.
20
Hirsch HH, Brennan DC, Drachenberg CB, et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations[J]. Transplantation, 2005, 79(10): 1277-1286.
21
Bicalho CS, Oliveira RDR, David DR, et al. Determination of viremia cut-off for risk to develop BKPyV-associated nephropathy among kidney transplant recipients[J]. Transpl Infect Dis, 2018, 20(5): e12969.
22
Sood P, Senanayake S, Sujeet K, et al. Management and outcome of BK viremia in renal transplant recipients: a prospective single center study[J]. Transplantation, 2012, 94(8): 814-821.
23
Hirsch HH, Drachenberg CB, Steiger J, et al. Polyomavirus-associated nephropathy in renal transplantation: critical issues of screening and management[J]. Adv Exp Med Biol, 2006, 577: 160-173.
24
Pollara CP, Corbellini S, Chiappini S, et al. Quantitative viral load measurement for BKV infection in renal transplant recipients as a predictive tool for BKVAN[J]. New Microbiol, 2011, 34(2): 165-171.
25
Johnston O, Jaswal D, Gill JS, et al. Treatment of polyomavirus infection in kidney transplant recipients: a systematic review[J]. Transplantation, 2010, 89(9): 1057-1070.
26
Ginevri F, Azzi A, Hirsch HH, et al. Prospective monitoring of polyomavirus BK replication and impact of preemptive intervention in pediatric kidney recipients[J]. Am J Transplant, 2007, 7(12): 2727-2735.
27
Saad ER, Bresnahan BA, Cohen EP, et al. Successful treatment of BK viremia using reduction in immunosuppression without antiviral therapy[J]. Transplantation, 2008, 85(6): 850-854.
28
Huang G, Wang CX, Zhang L, et al. Monitoring of polyomavirus BK replication and impact of preemptive immunosuppression reduction in renal transplant recipients in China: a 5-year single-center analysis[J]. Diagn Microbiol Infect Dis, 2015, 81(1): 21-26.
29
Loupy A, Lefaucheur C, Vernerey D, et al. Complement-binding anti-HLA antibodies and kidney-allograft survival[J]. N Engl J Med, 2013, 369(13): 1215-1226.
30
Krisl JC, Taber DJ, Pilch N, et al. Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection[J]. Clin J Am Soc Nephrol, 2012, 7(6): 1003-1009.
31
Hirsch HH, Randhawa PS, AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice[J]. Clin Transplant, 2019, 33(9): e13528.
[1] 彭文翰. 肾移植受者早期霉酚酸强化剂量长期有效性和安全性的研究[J]. 中华移植杂志(电子版), 2023, 17(05): 0-.
[2] 中华医学会器官移植学分会, 中国医师协会器官移植医师分会, 上海医药行业协会. 中国肝、肾移植受者霉酚酸类药物应用专家共识(2023版)[J]. 中华移植杂志(电子版), 2023, 17(05): 257-272.
[3] 彭雨诗, 苗芸, 严紫嫣. 宏基因组高通量测序诊断肾移植术后华支睾吸虫感染一例[J]. 中华移植杂志(电子版), 2023, 17(05): 297-299.
[4] 戚若晨, 马帅军, 韩士超, 王国辉, 刘克普, 张小燕, 杨晓剑, 秦卫军. 肾移植术后新型冠状病毒感染单中心诊疗经验[J]. 中华移植杂志(电子版), 2023, 17(04): 232-239.
[5] 胡皓翀, 刘一霆, 郭嘉瑜, 邹寄林, 陈忠宝, 周江桥, 邱涛. 肾移植术后耐碳青霉烯类肺炎克雷伯菌感染的诊疗分析[J]. 中华移植杂志(电子版), 2023, 17(04): 246-249.
[6] 朱伟芳, 陈琳, 乔建军. 激光联合光动力疗法治疗肾移植后鲍恩样丘疹病一例[J]. 中华移植杂志(电子版), 2023, 17(04): 250-252.
[7] 吴建永. 单中心2 000例心脏死亡器官捐献肾移植发展与创新[J]. 中华移植杂志(电子版), 2023, 17(04): 0-.
[8] 刘路浩, 苏泳鑫, 曾丽娟, 张鹏, 陈荣鑫, 徐璐, 李光辉, 方佳丽, 马俊杰, 陈正. 新型冠状病毒感染疫情期间肾移植受者免疫抑制剂服药依从性研究[J]. 中华移植杂志(电子版), 2023, 17(03): 140-145.
[9] 张亚龙, 邱涛, 刘一霆, 王天宇, 孔晨阳, 喻博, 周江桥. 术前透析方式及时长对肾移植预后的影响[J]. 中华移植杂志(电子版), 2023, 17(02): 98-103.
[10] 张修源, 吕军好, 陈大进. 2022年肾移植领域研究进展[J]. 中华移植杂志(电子版), 2023, 17(01): 32-35.
[11] 朱晨晨, 韩飞, 寿张飞. HCV阳性供肾移植单中心回顾性研究[J]. 中华移植杂志(电子版), 2023, 17(01): 47-53.
[12] 李娜, 王丹. 肾移植受者HCV感染研究进展[J]. 中华移植杂志(电子版), 2023, 17(01): 58-62.
[13] 李娜, 丁小明, 丁晨光, 王丹. 索非布韦联合雷迪帕韦在肾移植HCV感染受者中的应用[J]. 中华移植杂志(电子版), 2022, 16(06): 359-364.
[14] 中国医师协会器官移植医师分会, 中华医学会器官移植学分会, 中华医学会外科学分会移植学组, 中国医院协会器官获取与分配工作委员会. 中国心脏死亡捐献器官评估与应用专家共识(2022版)[J]. 中华移植杂志(电子版), 2022, 16(06): 321-328.
[15] 邱成, 戴帅, 张乐希, 刘洪涛. 初始血型抗体效价水平对ABO血型不相合活体肾移植受体肾功能及免疫功能的影响[J]. 中华临床医师杂志(电子版), 2022, 16(10): 1005-1011.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号