nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-37Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES CLINICAL STUDIESЧастота и динамика полиомавирусной инфекции после трансплантации почекFrequency and time dynamics of polyomavirus infection following renal transplantationЧухловинА. Б.ChukhlovinA. B.alexei.chukh@mail.ruЭйсмонтЮ. А.EismontYU. A.noemail@neicon.ruДобронравовВ. А.DobronravovV. A.noemail@neicon.ruБушМ. В.BuschM. V.noemail@neicon.ruЭмануэльВ. Л.EmanuelV. L.noemail@neicon.ruСмирновА. В.SmirnovA. V.noemail@neicon.ruНИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой Первого Санкт-Петербургского государственного медицинского университета им. акад. И.П. ПавловаRussian FederationНаучно-исследовательский институт нефрологии Первого Санкт-Петербургского государственного медицинского университета им. акад. И.П. ПавловаRussian FederationПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаRussian Federation2014010720141845156Copyright © Чухловин А.Б., Эйсмонт Ю.А., Добронравов В.А., Буш М.В., Эмануэль В.Л., Смирнов А.В., 20142014Чухловин А.Б., Эйсмонт Ю.А., Добронравов В.А., Буш М.В., Эмануэль В.Л., Смирнов А.В.Chukhlovin A.B., Eismont Y.A., Dobronravov V.A., Busch M.V., Emanuel V.L., Smirnov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/37

ЦЕЛЬ ИССЛЕДОВАНИЯ. Определение частоты детекции полиомавирусов BK и JC в моче и крови у больных после трансплантации почки (ТП) в зависимости от возраста и сроков после трансплантации. ПАЦИЕНТЫ И МЕТОДЫ. В исследование были включены 52 больных после ТП, в том числе 23 - с хроническим гломерулонефритом/нефросклерозом, 14 - с диабетической нефропатией, 8 - с IgA-нефропатией. Все больные получали стандартную иммуносупрессивную терапию. ДНК выделяли из клеток мочевого осадка и лейкоцитов периферической крови. Наличие вирусов BK и JC определяли методом геноспецифической ПЦР РЕЗУЛЬТАТЫ. Частота выявления полиомавирусов в клетках мочи составила, соответственно, 25 и 14% для вирусов ВК и JC. Полиомавирусы в периферической крови обнаружены в 33% (вирус ВК) и 28% проб (вирус JC). Вирурия и виремия для каждого типа полиомавирусов не были связаны друг с другом при отчетливой тенденции к сочетанному выявлению вирусов ВК и JC и в клетках мочи, и в лейкоцитах крови. Отмечена тенденция к повышению JC-позитивности в моче у больных старше 50 лет. Ко-инфекция вирусами ВК и JC определяется в 8% образцов мочи и 13% проб лейкоцитов. Частота JC-позитивных образцов мочи у больных с исходной диабетической нефропатией была достоверно выше, чем у остальных пациентов (33 против 23%, р=0,04), будучи особенно выраженной на 2-м году после ТП. ЗАКЛЮЧЕНИЕ. Полученные данные указывают на относительно высокую частоту выявления вирусов ВК и JC, включая ко-инфекцию, в клетках мочи и лейкоцитах крови и ее вероятную связь с возрастом, сроками после ТП и диабетом. Уточнение клинического и биологического значения полученных данных требует проведения дальнейших исследований.

AIM OF THE STUDY was to determine the detection rates for BK and JC polyomaviruses in urine sediment and blood leucocytes of patients after kidney transplantation (Tx), dependent on patients’ age and duration of post-transplant follow-up. PATIENTS AND METHODS. The study involved 52 patients (pts) after Tx, including those with chronic glomerulonephritis/nephropathies (n=38), diabetic nephropathy (n=14). All patients received immunosuppression based on calcineurin inhibitors, MMF and prednosone. DNA was isolated from urinary sediments and peripheral blood leukocytes. BK and JC DNA were determined by means of gene-specific polymerase chain reaction (PCR). RESULTS. Incidence of polyomaviruses in urine was 25% and 14% for ВК and JC, respectively. Blood samples were PCR-positive for ВК (33% of samples), and JC (28%). Viruria and viremia were not significantly associated, while a distinct correlation was found between BK- and JC-positivity either in urine sediment or in blood leucocytes. BK/JC co-infection was found in 8% of urinary specimens, and 13% of blood specimens. Urine JC positivity in patients with diabetic nephropathy increased, as compared to other groups (33% vs 23%, р=0,04), being especially high during 2nd year post-Tx. CONCLUSION. Our data are indicative for rather high BK and JC positivity, including co-infection (BK+JC), both in urinary and blood cells. Age, post-Tx period and diabetes are suggested to be a potential confounders. Clinical and biological value of the data obtained requires further studies.

трансплантация почкииммуносупрессияполиомавирусвирус ВКвирус JCмочакровьПЦР-диагностикаkidney transplantationimmune suppressionpolyomavirusBK virusJC virusurinebloodPCR-diagnosticsReferencesDalianis T, Hirsch HH. Human polyomaviruses in disease and cancer. Virology 2013; 437(2) :63-72Dalianis T, Hirsch HH. Human polyomaviruses in disease and cancer. Virology 2013; 437(2) :63-72Binet I, Nickeleit V, Hirsch HH, Prince O, Dalquen P, Gudat F, Mihatsch MJ, Thiel G., Mihatsch MJ. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 1999;67(6):918-922Binet I, Nickeleit V, Hirsch HH, Prince O, Dalquen P, Gudat F, Mihatsch MJ, Thiel G., Mihatsch MJ. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 1999;67(6):918-922Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, Steiger J. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. New Engl J Med 2002; 347(7):488-496Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, Steiger J. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. New Engl J Med 2002; 347(7):488-496Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille V, Andre-Garnier E, Imbert-Marcille BM. A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant 2005; 5(8):1926-1933Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille V, Andre-Garnier E, Imbert-Marcille BM. A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant 2005; 5(8):1926-1933Egli A, Binggeli S, Bodaghi S, Dumoulin A, Funk GA, Khanna N, Leuenberger D, Gosert R, Hirsch HH. Cytomegalovirus and polyomavirus BK posttransplant. Nephrol Dial Transplant 2007; 22 [Suppl 8]: viii72-viii82Egli A, Binggeli S, Bodaghi S, Dumoulin A, Funk GA, Khanna N, Leuenberger D, Gosert R, Hirsch HH. Cytomegalovirus and polyomavirus BK posttransplant. Nephrol Dial Transplant 2007; 22 [Suppl 8]: viii72-viii82Nickeleit V, Mihatsch MJ. Polyomavirus nephropathy in native kidneys and renal allografts: an update on an escalating threat. Transpl Int 2006; 19(12): 960-973Nickeleit V, Mihatsch MJ. Polyomavirus nephropathy in native kidneys and renal allografts: an update on an escalating threat. Transpl Int 2006; 19(12): 960-973Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses in human disease. Virology. 2009 20; 384(2): 266-273Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses in human disease. Virology. 2009 20; 384(2): 266-273Husseiny MI, Anastasi B, Singer J, Lacey SF. A comparative study of Merkel cell, BK and JC polyomavirusinfections in renal transplant recipients and healthy subjects. J Clin Virol 2010; 49(2): 137-140Husseiny MI, Anastasi B, Singer J, Lacey SF. A comparative study of Merkel cell, BK and JC polyomavirusinfections in renal transplant recipients and healthy subjects. J Clin Virol 2010; 49(2): 137-140Суханов АВ. Полиомавирусная нефропатия трансплантата. Нефрология и диализ, 2001, 3(4): 411-414Суханов АВ. Полиомавирусная нефропатия трансплантата. Нефрология и диализ, 2001, 3(4): 411-414Горбатенко ЕВ, Момыналиев КТ, Грибанов ОГ и др. Полиомавирус (BKV) у реципиентов с трансплантированной почкой (обзор литературы). Нефрология и диализ 2010, 12(3): 164-173Горбатенко ЕВ, Момыналиев КТ, Грибанов ОГ и др. Полиомавирус (BKV) у реципиентов с трансплантированной почкой (обзор литературы). Нефрология и диализ 2010, 12(3): 164-173Tan CS, Ellis LC, Wuethrich C, Ngo L, Broge Th A, Jr, Saint-Aubyn J, Miller JS, Koralnik IJ. JC Virus latency in the brain and extraneural organs of patients with and without progressive multifocal leukoencephalopathy. J Virol 2010, 84(18) :9200-9209Tan CS, Ellis LC, Wuethrich C, Ngo L, Broge Th A, Jr, Saint-Aubyn J, Miller JS, Koralnik IJ. JC Virus latency in the brain and extraneural organs of patients with and without progressive multifocal leukoencephalopathy. J Virol 2010, 84(18) :9200-9209Bellizzi A, Nardis C, Anzivino E, Rod o D, Fioriti D, Mischitelli M, Chiarini F, Pietropaolo V. Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies. J Neurovirol 2012;18(1):1-11Bellizzi A, Nardis C, Anzivino E, Rod o D, Fioriti D, Mischitelli M, Chiarini F, Pietropaolo V. Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies. J Neurovirol 2012;18(1):1-11Cheng XS, Bohl DL, Storch GA, Ryschkewitsch C, Gaudreault -Keener M, Major EO, Randhawa P, Hardinger KL., Brennan DC. Inhibitory interactions between BK and JC virus among kidney transplant recipients. J Am Soc Nephrol 2011; 22: 825-831Cheng XS, Bohl DL, Storch GA, Ryschkewitsch C, Gaudreault -Keener M, Major EO, Randhawa P, Hardinger KL., Brennan DC. Inhibitory interactions between BK and JC virus among kidney transplant recipients. J Am Soc Nephrol 2011; 22: 825-831Randhawa PS., Gupta G, Vats A, Shapiro R, Viscidi RP Immunoglobulin G, A, and M responses to BK virus in renal transplantation Clinical and Vaccine Immunol 2006; 13(9): 1057-1063Randhawa PS., Gupta G, Vats A, Shapiro R, Viscidi RP Immunoglobulin G, A, and M responses to BK virus in renal transplantation Clinical and Vaccine Immunol 2006; 13(9): 1057-1063Holman CJ, van Burik JAH, Hinrichs SH, Balfour HH, Jr. Specific detection of human BK polyomavirus in urine samples of immunocompromised patients. Clin Diagn Lab Immunol 2003; 10(1): 66-69Holman CJ, van Burik JAH, Hinrichs SH, Balfour HH, Jr. Specific detection of human BK polyomavirus in urine samples of immunocompromised patients. Clin Diagn Lab Immunol 2003; 10(1): 66-69Shin SK, Li MS, Fuerst F, Hotchkiss E, Meyer R, Kim TI, Goel A, Boland CR. Oncogenic T-antigen of JC virus is present frequently in human gastric cancers. Cancer 2006; 107:481-488Shin SK, Li MS, Fuerst F, Hotchkiss E, Meyer R, Kim TI, Goel A, Boland CR. Oncogenic T-antigen of JC virus is present frequently in human gastric cancers. Cancer 2006; 107:481-488Seemayer CA., Seemayer NH, Duermueller U, Gudat F, Schaub S, Hirsch HH, Mihatsch MJ. BK virus large T and VP-1 expression in infected human renal allografts. Nephrol Dial Transplant 2008; 23: 3752-3761Seemayer CA., Seemayer NH, Duermueller U, Gudat F, Schaub S, Hirsch HH, Mihatsch MJ. BK virus large T and VP-1 expression in infected human renal allografts. Nephrol Dial Transplant 2008; 23: 3752-3761Bechert CJ, Schnadig VJ, Payne DA, Dong J. Monitoring of BK viral load in renal allograft recipients by real-time PCR assays. Am J Clin Pathol 2010;133:242-250Bechert CJ, Schnadig VJ, Payne DA, Dong J. Monitoring of BK viral load in renal allograft recipients by real-time PCR assays. Am J Clin Pathol 2010;133:242-250Drachenberg CB, Hirsch HH, Papadimitriou JC, et al. Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation. Transplantation. 2007; 84(3):323-330Drachenberg CB, Hirsch HH, Papadimitriou JC, et al. Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation. Transplantation. 2007; 84(3):323-330Sood P, Senanayake S, Sujeet K, et al. Management and outcome of BK viremia in renal transplant recipients: a prospective single center study. Transplantation 2012;94:814-821Sood P, Senanayake S, Sujeet K, et al. Management and outcome of BK viremia in renal transplant recipients: a prospective single center study. Transplantation 2012;94:814-821Chatterjee M, Weyandt TB, Frisque RJ. Identification of archetype and rearranged forms of BK virus in leukocytes from healthy individuals. J. Med. Virol. 2000; 60:353-362Chatterjee M, Weyandt TB, Frisque RJ. Identification of archetype and rearranged forms of BK virus in leukocytes from healthy individuals. J. Med. Virol. 2000; 60:353-362Dörries K, Sbiera S, Drews K, Arendt G, Eggers C, Dörries R.J Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals.Neur ovirol. 2003;9 Suppl 1:81-87Dörries K, Sbiera S, Drews K, Arendt G, Eggers C, Dörries R.J Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals.Neur ovirol. 2003;9 Suppl 1:81-87Mertz KD, Junt T, Schmid M, Pfaltz M, Kempf W.I nflammatory monocytes are a reservoir for Merkel cell polyomavirus. J Invest Dermatol. 2010 Apr;130(4):1146-51Mertz KD, Junt T, Schmid M, Pfaltz M, Kempf W.I nflammatory monocytes are a reservoir for Merkel cell polyomavirus. J Invest Dermatol. 2010 Apr;130(4):1146-51Brennan DC, Agha I, Schnitzler MA, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005;5:582-594Brennan DC, Agha I, Schnitzler MA, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005;5:582-594Koukoulaki M, Grispou E, Pistolas D, et al. Prospective monitoring of BK virus replication in renal transplant recipients. Transpl Infect Dis 2009; 11: 1 -10Koukoulaki M, Grispou E, Pistolas D, et al. Prospective monitoring of BK virus replication in renal transplant recipients. Transpl Infect Dis 2009; 11: 1 -10Hirsch 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. Am J Transplant 2013; 13:136 -145Hirsch 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. Am J Transplant 2013; 13:136 -145Almeras 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. Transpl Infect Dis 2011;13:101-108Almeras 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. Transpl Infect Dis 2011;13:101-108López V, Gutiérrez C, Burgos D, et al. Prospective study of infection and nephropathy due to BK and JC polyomavirus in 76 kidney transplant recipients. Transplantation Proceedings. 2008;40(9):2927-2929López V, Gutiérrez C, Burgos D, et al. Prospective study of infection and nephropathy due to BK and JC polyomavirus in 76 kidney transplant recipients. Transplantation Proceedings. 2008;40(9):2927-2929Helanterä I, Ortiz F, Auvinen E, et al. Polyomavirus BK and JC infections in well matched Finnish kidney transplant recipients. Transplant International. 2009;22(7):688-693Helanterä I, Ortiz F, Auvinen E, et al. Polyomavirus BK and JC infections in well matched Finnish kidney transplant recipients. Transplant International. 2009;22(7):688-693Yin WY, Lu MC, Lee MC, Liu SC, Lin TY ,Lai NS. A correlation between polyomavirus JC virus quantification and genotypes in renal transplantation. American Journal of Surgery. 2010;200(1):53-58Yin WY, Lu MC, Lee MC, Liu SC, Lin TY ,Lai NS. A correlation between polyomavirus JC virus quantification and genotypes in renal transplantation. American Journal of Surgery. 2010;200(1):53-58Lopez V, Gutierrez C, Sola E, et al. Does JC polyomavirus cause nephropathy in renal transplant patients? Transplantation Proceedings. 2010;42(8):2889-2891Lopez V, Gutierrez C, Sola E, et al. Does JC polyomavirus cause nephropathy in renal transplant patients? Transplantation Proceedings. 2010;42(8):2889-2891Hu JH, Zhao H, Huang YP, et al. Opportunistic posttransplantation virus infections in renal transplant recipients. Transplantation Proceedings. 2011;43(10):3715-3719Hu JH, Zhao H, Huang YP, et al. Opportunistic posttransplantation virus infections in renal transplant recipients. Transplantation Proceedings. 2011;43(10):3715-3719Pires EP, Bernardino-Vallinoto CV, Alves DM, et al. Prevalence of infection by JC and BK polyomaviruses in kidney transplant recipients and patients with chronic renal disease. Transplant Infectious Disease. 2011;13(6):633-637Pires EP, Bernardino-Vallinoto CV, Alves DM, et al. Prevalence of infection by JC and BK polyomaviruses in kidney transplant recipients and patients with chronic renal disease. Transplant Infectious Disease. 2011;13(6):633-637Mengelle C, Kamar N, Mansuy JM, et al. JC virus DNA in the peripheral blood of renal transplant patients: a 1-year prospective follow-up in France. Journal of Medical Virology. 2011;83(1):132-136Mengelle C, Kamar N, Mansuy JM, et al. JC virus DNA in the peripheral blood of renal transplant patients: a 1-year prospective follow-up in France. Journal of Medical Virology. 2011;83(1):132-136Taheri S, Kafilzadeh F, Shafa M, et al. Comparison of polyomavirus (BK virus and JC viruses) viruria in renal transplant recipients with and without kidney dysfunction. Journal of Research in Medical Sciences. 2011;16(7):916-922Taheri S, Kafilzadeh F, Shafa M, et al. Comparison of polyomavirus (BK virus and JC viruses) viruria in renal transplant recipients with and without kidney dysfunction. Journal of Research in Medical Sciences. 2011;16(7):916-922Saundh BK, Tibble S, Baker R, Sasnauskas K, Harris M, Hale A. Different patterns of BK and JC polyomavirus reactivation following renal transplantation. Journal of Clinical Pathology. 2010;63(8):714-718Saundh BK, Tibble S, Baker R, Sasnauskas K, Harris M, Hale A. Different patterns of BK and JC polyomavirus reactivation following renal transplantation. Journal of Clinical Pathology. 2010;63(8):714-718Gu ZY Li Q, Si YL, Li X, Hao HJ, Song HJ. Prevalence of BK virus and JC virus in peripheral blood leukocytes and normal arterial walls in healthy individuals in China. J Med Virol 2003; 70(4):600-605Gu ZY Li Q, Si YL, Li X, Hao HJ, Song HJ. Prevalence of BK virus and JC virus in peripheral blood leukocytes and normal arterial walls in healthy individuals in China. J Med Virol 2003; 70(4):600-605Delbue S, Tremolada S, Elia F, Carloni C, Amico S, Tavazzi E, Marchioni E, Novati S, Maserati R, Ferrante P. Lymphotropic polyomavirus is detected in peripheral blood from immunocompromised and healthy subjects. J Clin Virol 2010;47(2): 156. doi:10.1016/j.jcv.2009.11.029Delbue S, Tremolada S, Elia F, Carloni C, Amico S, Tavazzi E, Marchioni E, Novati S, Maserati R, Ferrante P. Lymphotropic polyomavirus is detected in peripheral blood from immunocompromised and healthy subjects. J Clin Virol 2010;47(2): 156. doi:10.1016/j.jcv.2009.11.029Razonable RR, Brown RA, Humar A, Covington E, Alecock E, Paya CV. A longitudinal molecular surveillance study of human polyomavirus viremia in heart, kidney, liver, and pancreas transplant patients. J Infect Dis 2005; 192:1349-1354Razonable RR, Brown RA, Humar A, Covington E, Alecock E, Paya CV. A longitudinal molecular surveillance study of human polyomavirus viremia in heart, kidney, liver, and pancreas transplant patients. J Infect Dis 2005; 192:1349-1354Zhong S, Zheng HY Suzuki M, Chen Q, Ikegaya H, Aoki N, Usuku S, Kobayashi N, Nukuzuma S, Yasuda X Kuniyoshi N, Yogo X Kitamura T. Age-related urinary excretion of BK polyomavirus by nonimmunocompromised individuals. J Clin Microbiol 2007; 45(1): 193-198Zhong S, Zheng HY Suzuki M, Chen Q, Ikegaya H, Aoki N, Usuku S, Kobayashi N, Nukuzuma S, Yasuda X Kuniyoshi N, Yogo X Kitamura T. Age-related urinary excretion of BK polyomavirus by nonimmunocompromised individuals. J Clin Microbiol 2007; 45(1): 193-198Hogan TF, Borden EC, McBain JA, Padgett BL, Walker DL. Human polyomavirus infections with JC virus and BK virus in renal transplant patients. Ann Intern Med 1980; 92(3):373-378Hogan TF, Borden EC, McBain JA, Padgett BL, Walker DL. Human polyomavirus infections with JC virus and BK virus in renal transplant patients. Ann Intern Med 1980; 92(3):373-378

The authors declare that there are no conflicts of interest present.