-
摘要: 探讨BK病毒感染对肾移植受体预后的影响及目前相关研究进展,以期为临床提供有效的诊断和治疗措施。肾移植术后BK病毒感染率较高,可导致BK病毒相关性肾病(BKVN),甚至移植肾功能丢失。BK病毒感染诊断主要依靠实时荧光定量聚合酶链反应技术检测血液和尿液中BK病毒载量,BKVN诊断则需移植肾穿刺活组织检查。肾移植术后BK病毒感染对受者的影响较大,但目前缺乏有效的治疗手段,所以应在肾移植术后定期、规律检测BK病毒,早期发现、尽早干预,治疗上合理使用免疫抑制剂。
-
图 1 肾移植术后BK病毒感染的筛查及治疗
注:本图引自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.
Figure 1. Screening and treatment of BK virus infection after renal transplantation
-
[1] 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. http://cn.bing.com/academic/profile?id=1989209244&encoded=0&v=paper_preview&mkt=zh-cn [2] Bofill-Mas S, Formiga-Cruz M, Clemente-Casares P, et al. Potential transmission of human polyomaviruses through the gastrointestinal tract after exposure to virions or viral DNA[J]. J Virol,2001,75(21):10290-10299. doi: 10.1128/JVI.75.21.10290-10299.2001 [3] Cole CN, Conzen SD. Polyomaviridae the viruses and their replication[M]//Knipe DM, Howley PM. Fields virology, Vol Ⅱ. Philadelphia: Lippinoctt Williams&Wilkins, 2001: 2141-2157. [4] Tremolada S, Akan S, Otte J, et al. Rare subtypes of BK virus are viable and frequently detected in renal transplant recipients with BK virus-associated nephropathy[J]. Virology,2010,404(2):312-318. doi: 10.1016/j.virol.2010.05.012 [5] Takasaka T, Goya N, Tokumoto T, et al. Subtypes of BK virus prevalent in Japan and variation in their transcriptional control region[J]. J Gen Virol,2004,85(Pt 10):2821-2827. http://cn.bing.com/academic/profile?id=2096039751&encoded=0&v=paper_preview&mkt=zh-cn [6] Drachenberg CB, Papadimitriou JC, Hirsch HH, et al. Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load[J]. Am J Transplant,2004,4(12):2082-2092. doi: 10.1046/j.1600-6143.2004.00603.x [7] Egli A, Infanti L, Dumoulin A, et al. Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors[J]. J Infect Dis, 2009, 199(6):837-846. doi: 10.1086/598679 [8] Brown DW, Gardner SD, Gibson PE, et al. BK virus specific IgM responses in cord sera, young children and healthy adults detected by RIA[J]. Arch Virol,1984,82(3/4):149-160. http://cn.bing.com/academic/profile?id=1999247511&encoded=0&v=paper_preview&mkt=zh-cn [9] 邓伟明, 苗芸. 肾移植术后 BK 病毒相关性肾病的临床诊治研究进展[J].器官移植,2015,6(2):120-123,130. http://www.cnki.com.cn/Article/CJFDTOTAL-QGYZ201502011.htmDeng WM, Miao Y. Clinical research progress on diagnosis and treatment of BK virus-associated nephropathy after renal transplantation[J]. Organ Transplant,2015,6(2):120-123,130. http://www.cnki.com.cn/Article/CJFDTOTAL-QGYZ201502011.htm [10] Alméras C, Vetromile F, Garrigue V, et al. Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients[J]. Transpl Infect Dis, 2011, 13(2):101-108. doi: 10.1111/tid.2011.13.issue-2 [11] 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. doi: 10.1097/TP.0b013e31826690c6 [12] 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. doi: 10.1111/j.1600-6143.2012.04320.x [13] Acott PD, Hirsch HH. BK virus infection, replication, and diseases in pediatric kidney transplantation[J]. Pediatr Nephrol, 2007, 22(9):1243-1250. doi: 10.1007/s00467-007-0462-x [14] Pham PT, Reddy UG. Transplantation: immunosuppression and risk of polyomavirus BK replication[J]. Nat Rev Nephrol,2013,9(3):135-136. doi: 10.1038/nrneph.2013.17 [15] Bohl DL, Storch GA, Ryschkewitsch C, et al. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia[J]. Am J Transplant,2005,5(9):2213-2221. doi: 10.1111/ajt.2005.5.issue-9 [16] Dadhania D, Snopkowski C, Ding R, et al. Epidemiology of BK virus in renal allograft recipients: independent risk factors for BK virus replication[J]. Transplantation, 2008, 86(4):521-528. doi: 10.1097/TP.0b013e31817c6447 [17] Sharif A, Alachkar N, Bagnasco S, et al. Incidence and outcomes of BK virus allograft nephropathy among ABO- and HLA-incompatible kidney transplant recipients[J]. Clin J Am Soc Nephrol, 2012,7(8):1320-1327. doi: 10.2215/CJN.00770112 [18] Saundh BK, Baker R, Harris M, et al. Early BK polyomavirus (BKV) reactivation in donor kidney is a risk factor for development of BKV-associated nephropathy[J]. J Infect Dis, 2013, 207(1):137-141. doi: 10.1093/infdis/jis642 [19] Masutani K, Ninomiya T, Randhawa P. HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia[J]. Nephrol Dial Transplant,2013, 28(12):3119-3126. doi: 10.1093/ndt/gft298 [20] Hssig A, Roos M, Etter A, et al. Association of BK viremia with human leukocyte antigen mismatches and acute rejection, but not with type of calcineurin inhibitor[J]. Transpl Infect Dis, 2014, 16(1):44-54. doi: 10.1111/tid.2014.16.issue-1 [21] 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 [22] Singh HK, Andreoni KA, Madden V, et al. Presence of urinary Haufen accurately predicts polyomavirus nephropathy[J]. J Am Soc Nephrol,2009,20(2):416-427. doi: 10.1681/ASN.2008010117 [23] 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 [24] Kuppachi S, Thomas B, Kokko KE. BK virus in the kidney transplant patient[J]. Am J Med Sci,2013, 345(6):482-488. doi: 10.1097/MAJ.0b013e31826c64ef [25] 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. doi: 10.1007/0-387-32957-9 [26] 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. doi: 10.1097/01.TP.0000156165.83160.09 [27] Viscount HB, Eid AJ, Espy MJ, et al. Polyomavirus polymerase chain reaction as a surrogate marker of polyomavirus-associated nephropathy[J]. Transplantation, 2007, 84(3):340-345. doi: 10.1097/01.tp.0000275205.41078.51 [28] Yeo FE, Yuan CM, Swanson SJ, et al. The prevalence of BK polyomavirus infection in outpatient kidney transplant recipients followed in a single center[J]. Clin Transplant,2008,22(5):532-541. doi: 10.1111/j.1399-0012.2008.00817.x [29] Boothpur R, Brennan DC. Human polyoma viruses and disease with emphasis on clinical BK and JC[J]. J Clin Virol, 2010, 47(4):306-312. doi: 10.1016/j.jcv.2009.12.006 [30] Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients[J]. Am J Transplant, 2009,9 (Suppl 3):S1-S155. http://cn.bing.com/academic/profile?id=1990827591&encoded=0&v=paper_preview&mkt=zh-cn [31] Vasudev B, Hariharan S, Hussain SA, et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients[J]. Kidney Int,2005,68(4):1834-1839. doi: 10.1111/j.1523-1755.2005.00602.x [32] Wali RK, Drachenberg CB, Hirsch HH, et al. Intensive versus routine care screening for polyoma viral replication (cluster randomization) and a road map for stepwise modification of immunosuppression therapy (Abstract)[J]. Am J Transplant, 2008,8(Supl 2): 283. [33] Egli A, Köhli S, Dickenmann M, et al. Inhibition of polyomavirus BK-specific T-cell responses by immunosuppressive drugs[J]. Transplantation, 2009, 88(10):1161-1168. doi: 10.1097/TP.0b013e3181bca422 [34] 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 [35] 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. doi: 10.1111/ajt.2010.10.issue-12 [36] Guasch A, Roy-Chaudhury P, Woodle ES, et al. Assessment of efficacy and safety of FK778 in comparison with standard care in renal transplant recipients with untreated BK nephropathy[J]. Transplantation,2010,90(8):891-897. http://cn.bing.com/academic/profile?id=2017707529&encoded=0&v=paper_preview&mkt=zh-cn