肾移植术后BK病毒感染对移植肾功能影响的临床研究

范宇; 石炳毅; 钱叶勇; 柏宏伟; 罗用文

doi:10.3969/j.issn.1674-7445.2018.01.007

肾移植术后BK病毒感染对移植肾功能影响的临床研究

doi: 10.3969/j.issn.1674-7445.2018.01.007

100091 北京，解放军第309医院移植外科

基金项目:

北京市科技计划课题 Z17110000107184

详细信息

作者简介:
范宇，男，1981年生，博士研究生，主治医师，研究方向为肾脏移植，Email: fleas003@163.com

通讯作者:
石炳毅，男，1953年生，博士，主任医师，博士研究生导师，研究方向为器官移植，Email: shibingyi@medmail.com.cn

中图分类号: R617, R692
计量
- 文章访问数: 204
- HTML全文浏览量: 133
- PDF下载量: 14
- 被引次数: 0
出版历程
- 收稿日期: 2017-09-15
- 网络出版日期: 2021-01-19
- 刊出日期: 2018-01-15

Clinical study on the effect of BK virus infection on renal allograft function after renal transplantation

Department of Transplant Surgery, the 309th Hospital of People's Liberation Army, Beijing 100091, China

More Information

Corresponding author: Shi Bingyi, Email: shibingyi@medmail.com.cn

摘要

摘要: 目的分析肾移植受体术后BK病毒感染导致移植肾功能受损的情况。方法回顾性分析行同种异体肾移植术并定期规律接受BK病毒监测的210例受体临床资料，总结肾移植术后BK病毒尿症、病毒血症和BK病毒性肾病（BKVN）的发生情况，分析BK病毒感染对移植肾功能的影响及BK病毒清除后移植肾功能转归情况。结果 210例受体中，单纯病毒尿症受体46例，病毒血症合并病毒尿症受体46例，病理学活组织检查证实的BKVN受体7例。移植术后病毒血症受体的血清肌酐（Scr）水平分别与尿液、血液BK病毒载量呈线性相关（r=0.594、0.672，均为P < 0.01）。病毒血症受体的血液BK病毒载量初次发现阳性时Scr水平即呈明显升高趋势，持续病毒血症状态时Scr水平会持续升高，经治疗血液病毒载量转阴后Scr水平略下降但仍明显高于病毒感染前水平，差异均有统计学意义（均为P < 0.05）。与基础水平比较，单纯病毒尿症受体病毒尿症阳性期间的Scr水平变化差异无统计学意义（均为P>0.05）。结论肾移植术后发生BK病毒血症时会对移植肾功能造成损伤，定期规律监测病毒感染很有必要，一旦发现血BK病毒阳性时应立即实施以降低免疫抑制强度为首选的临床干预治疗措施。
- 肾移植 /
- 移植肾功能 /
- BK病毒 /
- BK病毒尿症 /
- BK病毒血症 /
- BK病毒性肾病 /
- 血清肌酐
Abstract: Objective To analyze the impairment of renal allograft function in renal transplant recipients caused by BK virus infection after renal transplantation. Methods Clinical data of 210 recipients who underwent allogenic renal transplantation and received BK virus monitoring regularly were analyzed retrospectively. The incidence of BK viruria, viremia and BK virus nephropathy (BKVN) after renal transplantation was summarized. The effect of BK virus infection on renal allograft function and prognosis of renal allograft function after the removement of BK virus were analyzed. Results Among the 210 recipients, there were 46 cases with pure viruria, 46 cases with viremia complicated with viruria and 7 cases with BKVN confirmed by pathological biopsy. The level of serum creatinine (Scr) in the recipients with viremia after renal transplantation was linearly related to BK viral load in urine and blood (r=0.594, 0.672, both P < 0.01). The level of Scr increased significantly when BK viral load in blood of the recipients with viremia was found positive for the first time, and increased continuously after viremia sustained. And the level of Scr decreased slightly when blood viral load turned to negative after treatment, but still significantly higher than before virus infection. All the above differences were statistically significant (all P < 0.05). Compared with the basic level, there was no significant difference in the level of Scr of recipients with pure viruria during positive viruria (all P>0.05). Conclusions It will impair the renal allograft function when BK viremia occurs after renal transplantation, and it is necessary to monitor viral infection regularly. Once the blood BK virus is found positive, it shall be implemented immediately to reduce the intensity of immunosuppression as the preferred clinical intervention.
- Renal transplantation /
- Renal allograft function /
- BK virus /
- BK viruria /
- BK viremia /
- BK virus nephropathy /
- Serum creatinine

HTML全文

图 1 肾移植术后BK病毒血症受体Scr水平与尿液和血液BK病毒载量的线性相关图

Figure 1. The linear correlation between Scr level and BK virus load in urine and blood of recipients with BK viremia after renal transplantation

下载: 全尺寸图片幻灯片

图 2 单纯病毒尿症受体和病毒血症受体BK病毒感染时的Scr水平变化

Figure 2. Changes of Scr levels in recipients with simple viruria or with viremia after BK virus infection

下载: 全尺寸图片幻灯片

图 3 肾移植术后BK病毒感染受体病毒尿症和病毒血症阳性率的Kaplan-Meier曲线

Figure 3. Kaplan-Meier curve of BK viruria and viremia positive ratio in recipients with BK virus infection after renal transplantation

下载: 全尺寸图片幻灯片

图 4 肾移植术后BK病毒感染受体病毒载量转阴后Scr水平的变化

Figure 4. Changes of Scr levels in recipients with BK virus infection after renal transplantation with negative viral load

下载: 全尺寸图片幻灯片

参考文献(24)

[1]	HIRSCH HH, KNOWLES W, DICKENMANN M, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients[J]. N Engl J Med, 2002, 347(7): 488-496. DOI: 10.1056/NEJMoa020439.
[2]	HIRSCH HH, RANDHAWA P, AST Infectious Diseases Community of Practice. BK virus in solid organ transplant recipients[J]. Am J Transplant, 2009, 12(9): S136-S146. DOI: 10.1111/j.1600-6143.2009.02904.x.
[3]	GOLDBERG RJ, WENG FL, Kandula P. Acute and chronic allograft dysfunction in kidney transplant recipients[J]. Med Clin North Am, 2016, 100(3): 487-503. DOI: 10.1016/j.mcna.2016.01.002.
[4]	HAMMARIN AL, ÖQVIST B, WAHLGREN J, et al. Systematic screening of BK virus by real-time PCR prevents BK virus associated nephropathy in renal transplant recipients[J]. J Med Virol, 2011, 83(11): 1959-1965. DOI: 10.1002/jmv.22196.
[5]	HASAN MR, TAN R, AL-RAWAHI G, et al. Comparative evaluation of laboratory developed real-time PCR assays and RealStar(^®) BKV PCR Kit for quantitative detection of BK polyomavirus[J]. J Virol Methods, 2016, 234: 80-86. DOI: 10.1016/j.jviromet.2016.04.009.
[6]	SAWINSKI D, Goral S. BK virus infection: an update on diagnosis and treatment[J]. Nephrol Dial Transplant, 2015, 30(2):209-217. DOI: 10.1093/ndt/gfu023.
[7]	WRIGHT AJ, GILL JS. Strategies to prevent BK virus infection in kidney transplant recipients[J]. Curr Opin Infect Dis, 2016, 29(4): 353-358. DOI: 10.1097/QCO.0000000000000278.
[8]	解俊杰, 石炳毅, 钱叶勇, 等.肾移植后BK病毒感染者实时荧光定量PCR检测[J].中国组织工程研究, 2012, 16(5): 797-800. DOI: 10.3969/j.issn.1673-8225.2012.05.009. XIE JJ, SHI BY, QIAN YY, et al. BK virus infection detected by real-time fluorescent quantitative PCR method after renal transplantation[J]. Chin J Tissue Eng Res, 2012, 16(5): 797-800. DOI: 10.3969/j.issn.1673-8225.2012.05.009.
[9]	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. DOI: 10.1097/TP.0b013e3181d0e15e.
[10]	GARDNER SD, FIELD AM, COLEMAN DV, et al. New human papovavirus (B.K.) isolated from urine after renal transplantation[J]. Lancet, 1971, 1(7712): 1253-1257. DOI: 10.1016/S0140-6736(71)90562-9.
[11]	PURIGHALLA R, SHAPIRO R, MCCAULEY J, et al. BK virus infection in a kidney allograft diagnosed by needle biopsy[J]. Am J Kidney Dis, 1995, 26(4): 671-673. DOI: 10.1016/0272-6386(95)90608-8.
[12]	RANDHAWA PS, FINKELSTEIN S, SCANTLEBURY V, et al. Human polyoma virus-associated interstitial nephritis in the allograft kidney[J]. Transplantation, 1999, 67(67):103-109. DOI: 10.1097/00007890-199901150-00018.
[13]	DHARNIDHARKA VR, CHERIKH WS, ABBOTT KC. An OPTN analysis of national registry data on treatment of BK virus allograft nephropathy in the United States[J]. Transplantation, 2009, 87(7): 1019-1026. DOI: 10.1097/TP.0b013e31819cc383.
[14]	GIRMANOVA E, BRABCOVA I, BANDUR S, et al. A prospective longitudinal study of BK virus infection in 120 Czech renal transplant recipients[J]. J Med Virol, 2011, 83(8): 1395-1400. DOI: 10.1002/jmv.22106.
[15]	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. DOI: 10.1097/TP.0000000000001066.
[16]	HIRSCH HH. BK virus: opportunity makes a pathogen[J]. Clin Infect Dis, 2005, 41(3): 354-360. DOI: 10.1086/431488.
[17]	HARIHARAN S. BK virus nephritis after renal transplantation[J]. Kidney Int, 2006, 69(4): 655-662. DOI: 10.1038/sj.ki.5000040.
[18]	HIRSCH HH, STEIGER J. Polyomavirus BK[J]. Lancet Infect Dis, 2003, 3(10): 611-623. DOI: 10.1016/S1473-3099(03)00770-9.
[19]	JAMBOTI JS, BK virus nephropathy in renal transplant recipients[J]. Nephrology (Carlton), 2016, 21(8): 647-654. DOI: 10.1111/nep.12728.
[20]	GINEVRI F, DE SANTIS R, COMOLI P, et al. Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches[J]. Transplantation, 2003, 75(8): 1266-1270. DOI: 10.1097/01.TP.0000061767.32870.72.
[21]	MASUTANI, K, SHAPIRO R, BASU A, et al. The Banff 2009 working proposal for polyomavirus nephropathy: a critical evaluation of its utility as a determinant of clinical outcome[J]. Am J Transplant, 2012, 12(4): 907-918. DOI: 10.1111/j.1600-6143.2012.03993.x.
[22]	NICKELEIT V, KLIMKAIT T, BINET IF, et al. Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy[J]. N Engl J Med, 2000, 342(18): 1309-1315. DOI: 10.1056/NEJM200005043421802.
[23]	EL ANSARY M, ABD ELHAMID S, SAADI G, et al. Prevalence of polyoma BK virus infection among living-donor renal transplant recipients[J]. Transpl Infect Dis, 2016, 18(4): 529-537. DOI: 10.1111/tid.12557.
[24]	SAWINSKI D, FORDE KA, TROFE-CLARK J, et al. Persistent BK viremia does not increase intermediate-term graft loss but is associated with de novo donor-specific antibodies[J]. J Am Soc Nephrol, 2015, 26(4): 966-975. DOI: 10.1681/ASN.2014010119.