Pediatric Nephrology

, Volume 33, Issue 12, pp 2343–2352 | Cite as

JC polyomavirus replication and associated disease in pediatric renal transplantation: an international CERTAIN Registry study

  • Britta HöckerEmail author
  • Julia Tabatabai
  • Lukas Schneble
  • Jun Oh
  • Florian Thiel
  • Lars Pape
  • Krisztina Rusai
  • Rezan Topaloglu
  • Birgitta Kranz
  • Günter Klaus
  • Nikoleta Printza
  • Onder Yavascan
  • Alexander Fichtner
  • Kai Krupka
  • Thomas Bruckner
  • Rüdiger Waldherr
  • Michael Pawlita
  • Paul Schnitzler
  • Hans H. Hirsch
  • Burkhard Tönshoff
Original Article
Part of the following topical collections:
  1. What’s New in Renal Transplantation



JC polyomavirus (JCPyV)-associated nephropathy (JCPyVAN) is a severe, but rare complication in adult renal transplant (RTx) recipients. Related data in pediatric patients are scarce.


Based on the CERTAIN Registry, we therefore performed a multi-center, retrospective study on the JCPyV antibody status, prevalence of JCPyV replication, and its associated disease in 139 pediatric RTx recipients (mean age, 8.5 ± 5.3 years). JCPyV DNA in plasma and/or urine was measured by quantitative PCR at a median time of 3.2 (IQR, 0.3–8.1) years post-transplant.


53.2% of patients were JCPyV-seronegative prior to transplantation; younger age was associated with JCPyV seronegativity. 34/139 (24.5%) patients post-transplant showed active JCPyV replication in either urine (22.0%), plasma (13.4%), or both (7.6%). JCPyV viremia occurred significantly (p < 0.001) more often in patients with viruria (34.6%) than in those without (7.6%), but 7/118 (5.9%) had isolated viremia. High-level viruria (> 107 copies/mL) was found in 29.6% of viruric patients. A higher net state of immunosuppression constituted an independent risk factor for JCPyV replication both in urine and plasma (OR 1.2, p < 0.02). Male patients tended to have a higher risk of JCPyV viremia than females (OR 4.3, p = 0.057). There was one male patient (0.7%) with JCPyVAN 7 years post-transplant, which resolved after reduction of immunosuppressive therapy. No patient exhibited progressive multifocal leukoencephalopathy.


This first multi-center study on JCPyV in pediatric renal transplant recipients shows that JCPyV replication is common (24.5%), with strong immunosuppression being a significant risk factor, but associated nephropathy is rare.


JC polyomavirus JC virus Polyomavirus Nephropathy Pediatric renal transplantation Pediatric kidney transplantation 



The authors wish to thank study nurse Annette Mechler for her continuous excellent contributions to the CERTAIN Registry. BH is an awardee of the “DZIF Clinical Leave Stipend” from the German Center for Infection Research (DZIF).

Author contributions

BH: study design, data collection and analysis, preparation of manuscript, principal investigator. JT and LS: study design, data collection and analysis. JO, FT, LP, KR, RT, BK, GK, NP, OY, JT, AF, and KK: data collection. TB: statistical analysis. RW: histopathological evaluation. MP and PS: virological methodology and analyses, data collection. HHH: study design, preparation of the manuscript. BT: study design, data analyses, preparation of manuscript.

Funding information

The authors acknowledge their gratitude to the Dietmar Hopp Stiftung as well as to the pharmaceutical companies Astellas, Novartis, and Roche for their grants in support of the CERTAIN Registry.

Compliance with ethical standards

Conflict of interests

B.H. received travel grants and participated in advisory boards of Astellas, Novartis, and Roche. H.H.H. reported consultant and speaker honoraria by Novartis, and Chimerix. B.T. received research grants, travel grants, lecture fees, and participated in advisory boards of Astellas, Bristol-Myers Squibb, Novartis, and Roche. J.T., L.S., J.O., F.T., L.P., K.R., R.T. B.K., G.K. N.P., O.Y., A.F., K.K., T.B., R.W., M.P., and P.S. declare no conflict of interests.


  1. 1.
    Calvignac-Spencer S, Feltkamp MC, Daugherty MD, Moens U, Ramqvist T, Johne R, Ehlers B, Polyomaviridae Study Group of the International Committee on Taxonomy of V (2016) A taxonomy update for the family Polyomaviridae. Arch Virol 161:1739–1750CrossRefPubMedCentralGoogle Scholar
  2. 2.
    Zurhein G, Chou SM (1965) Particles resembling papova viruses in human cerebral demyelinating disease. Science 148:1477–1479CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH (1971) Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1:1257–1260CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Hirsch HH, Kardas P, Kranz D, Leboeuf C (2013) The human JC polyomavirus (JCPyV): virological background and clinical implications. APMIS 121:685–727CrossRefGoogle Scholar
  5. 5.
    Padgett BL, Rogers CM, Walker DL (1977) JC virus, a human polyomavirus associated with progressive multifocal leukoencephalopathy: additional biological characteristics and antigenic relationships. Infect Immun 15:656–662PubMedPubMedCentralGoogle Scholar
  6. 6.
    Egli A, Infanti L, Dumoulin A, Buser A, Samaridis J, Stebler C, Gosert R, Hirsch HH (2009) Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 199:837–846CrossRefPubMedCentralGoogle Scholar
  7. 7.
    Knowles WA, Pipkin P, Andrews N, Vyse A, Minor P, Brown DW, Miller E (2003) Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 71:115–123CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D (2005) Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 353:375–381CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Berger JR (2007) Progressive multifocal leukoencephalopathy. Curr Neurol Neurosci Rep 7:461–469CrossRefGoogle Scholar
  10. 10.
    Drachenberg CB, Hirsch HH, Papadimitriou JC, Gosert R, Wali RK, Munivenkatappa R, Nogueira J, Cangro CB, Haririan A, Mendley S, Ramos E (2007) Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation. Transplantation 84:323–330CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Kantarci G, Eren Z, Demirag A, Dogan I, Cakalagaoglu F, Yilmaz G (2011) JC virus-associated nephropathy in a renal transplant recipient and comparative analysis of previous cases. Transpl Infect Dis 13:89–92CrossRefPubMedCentralGoogle Scholar
  12. 12.
    Lautenschlager I, Jahnukainen T, Kardas P, Lohi J, Auvinen E, Mannonen L, Dumoulin A, Hirsch HH, Jalanko H (2014) A case of primary JC polyomavirus infection-associated nephropathy. Am J Transplant 14:2887–2892CrossRefPubMedCentralGoogle Scholar
  13. 13.
    Kazory A, Ducloux D, Chalopin JM, Angonin R, Fontaniere B, Moret H (2003) The first case of JC virus allograft nephropathy. Transplantation 76:1653–1655CrossRefPubMedCentralGoogle Scholar
  14. 14.
    Wen MC, Wang CL, Wang M, Cheng CH, Wu MJ, Chen CH, Shu KH, Chang D (2004) Association of JC virus with tubulointerstitial nephritis in a renal allograft recipient. J Med Virol 72:675–678CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Aubert O, Galmiche L, Rozenberg F, Duquesne A, Scemla A, Rabant M, Leruez M, Laude H, Legendre C, Sberro-Soussan R (2013) The case | post-tranplant allograft dysfunction. Kidney Int 83:765–767CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Helantera I, Hirsch HH, Auvinen E, Mannonen L, Nummi M, Wernli M, Ortiz F, Raisanen-Sokolowski A, Lempinen M, Lautenschlager I (2016) High-level JCPyV viruria after kidney transplantation-clinical and histopathological findings. J Clin Virol 85:75–79CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Helantera I, Ortiz F, Auvinen E, Raisanen-Sokolowski A, Lappalainen M, Lautenschlager I, Koskinen P (2009) Polyomavirus BK and JC infections in well matched Finnish kidney transplant recipients. Transpl Int 22:688–693CrossRefPubMedCentralGoogle Scholar
  18. 18.
    Saundh BK, Baker R, Harris M, Hale A (2016) A prospective study of renal transplant recipients reveals an absence of primary JC polyomavirus infections. J Clin Virol 77:101–105CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Koster L, Krupka K, Hocker B, Rahmel A, Samuel U, Zanen W, Opelz G, Susal C, Dohler B, Plotnicki L, Kohl CD, Knaup P, Tonshoff B (2015) Integrating data from multiple sources for data completeness in a web-based registry for pediatric renal transplantation—the CERTAIN Registry. Stud Health Technol Inform 216:1049PubMedPubMedCentralGoogle Scholar
  20. 20.
    Plotnicki L, Kohl CD, Hocker B, Krupka K, Rahmel A, Pape L, Hoyer P, Marks SD, Webb NJ, Soylemezoglu O, Topaloglu R, Szabo AJ, Seeman T, Marlies Cornelissen EA, Knops N, Grenda R, Tonshoff B (2013) The CERTAIN Registry: a novel, web-based registry and research platform for pediatric renal transplantation in Europe. Transplant Proc 45:1414–1417CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Chisolm JJHH, Eberlein WR, Harrison HE (1955) Aminoaciduria, hypophosphatemia, and rickets in lead poisoning. Am J Dis Child 89:159–168Google Scholar
  22. 22.
    Hocker B, Bohm S, Fickenscher H, Kusters U, Schnitzler P, Pohl M, John U, Kemper MJ, Fehrenbach H, Wigger M, Holder M, Schroder M, Feneberg R, Kopf-Shakib S, Tonshoff B (2012) (Val-)Ganciclovir prophylaxis reduces Epstein-Barr virus primary infection in pediatric renal transplantation. Transpl Int 25:723–731CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Hocker B, Fickenscher H, Delecluse HJ, Bohm S, Kusters U, Schnitzler P, Pohl M, John U, Kemper MJ, Fehrenbach H, Wigger M, Holder M, Schroder M, Billing H, Fichtner A, Feneberg R, Sander A, Kopf-Shakib S, Susal C, Tonshoff B (2013) Epidemiology and morbidity of Epstein-Barr virus infection in pediatric renal transplant recipients: a multicenter, prospective study. Clin Infect Dis 56:84–92CrossRefPubMedCentralGoogle Scholar
  24. 24.
    Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA, Cohen EP (2005) BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int 68:1834–1839CrossRefPubMedCentralGoogle Scholar
  25. 25.
    Cordts SE, Schneble L, Schnitzler P, Wenzel JJ, Vinke T, Rieger S, Fichtner A, Tonshoff B, Hocker B (2018) Prevalence, morbidity, and therapy of hepatitis E virus infection in pediatric renal allograft recipients. Pediatr Nephrol 33:1215–1225CrossRefPubMedCentralGoogle Scholar
  26. 26.
    Hocker B, Aguilar M, Schnitzler P, Pape L, Bald M, Konig J, Marks SD, Genc G, Buscher A, Kemper MJ, Billing H, Pohl M, Dello Strologo L, Webb NJA, Rieger S, Mankertz A, Krupka K, Bruckner T, Fichtner A, Tonshoff B (2018) Vaccination titres pre- and post-transplant in paediatric renal transplant recipients and the impact of immunosuppressive therapy. Pediatr Nephrol 33:897–910CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Hocker B, Zencke S, Krupka K, Fichtner A, Pape L, Dello Strologo L, Guzzo I, Topaloglu R, Kranz B, Konig J, Bald M, Webb NJ, Noyan A, Dursun H, Marks S, Yalcinkaya F, Thiel F, Billing H, Pohl M, Fehrenbach H, Bruckner T, Tonshoff B (2016) Cytomegalovirus infection in pediatric renal transplantation and the impact of chemoprophylaxis with (val-)ganciclovir. Transplantation 100:862–870CrossRefPubMedCentralGoogle Scholar
  28. 28.
    Green M (2017) Preventing CMV and EBV in children undergoing organ transplantation: retrospective studies can only teach us so much. Pediatr Transplant. CrossRefGoogle Scholar
  29. 29.
    Cameron BM, Kennedy SE, Rawlinson WD, Mackie FE (2017) The efficacy of valganciclovir for prevention of infections with cytomegalovirus and Epstein-Barr virus after kidney transplant in children. Pediatr Transplant. CrossRefGoogle Scholar
  30. 30.
    Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M, Banff meeting report writing c (2014) Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 14:272–283CrossRefPubMedCentralGoogle Scholar
  31. 31.
    Adam B, Randhawa P, Chan S, Zeng G, Regele H, Kushner YB, Colvin RB, Reeve J, Mengel M (2014) Banff initiative for quality assurance in transplantation (BIFQUIT): reproducibility of polyomavirus immunohistochemistry in kidney allografts. Am J Transplant 14:2137–2147CrossRefPubMedCentralGoogle Scholar
  32. 32.
    Kjaerheim K, Roe OD, Waterboer T, Sehr P, Rizk R, Dai HY, Sandeck H, Larsson E, Andersen A, Boffetta P, Pawlita M (2007) Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples. Int J Cancer 120:2459–2465CrossRefPubMedCentralGoogle Scholar
  33. 33.
    Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedCentralGoogle Scholar
  34. 34.
    Ettenger R, Chin H, Kesler K, Bridges N, Grimm P, Reed EF, Sarwal M, Sibley R, Tsai E, Warshaw B, Kirk AD (2017) Relationship among viremia/viral infection, alloimmunity, and nutritional parameters in the first year after pediatric kidney transplantation. Am J Transplant 17:1549–1562CrossRefPubMedCentralGoogle Scholar
  35. 35.
    Herman J, Van Ranst M, Snoeck R, Beuselinck K, Lerut E, Van Damme-Lombaerts R (2004) Polyomavirus infection in pediatric renal transplant recipients: evaluation using a quantitative real-time PCR technique. Pediatr Transplant 8:485–492CrossRefPubMedCentralGoogle Scholar
  36. 36.
    Vanchiere JA, White ZS, Butel JS (2005) Detection of BK virus and simian virus 40 in the urine of healthy children. J Med Virol 75:447–454CrossRefPubMedCentralGoogle Scholar
  37. 37.
    Chang H, Wang M, Tsai RT, Lin HS, Huan JS, Wang WC, Chang D (2002) High incidence of JC viruria in JC-seropositive older individuals. J Neuro-Oncol 8:447–451Google Scholar
  38. 38.
    Van Loy T, Thys K, Tritsmans L, Stuyver LJ (2013) Quasispecies analysis of JC virus DNA present in urine of healthy subjects. PLoS One 8:e70950CrossRefPubMedCentralGoogle Scholar
  39. 39.
    Hirsch HH, Randhawa P, Practice ASTIDCo (2013) BK polyomavirus in solid organ transplantation. Am J Transplant 13(Suppl 4):179–188CrossRefPubMedCentralGoogle Scholar
  40. 40.
    Chapagain ML, Nerurkar VR (2010) Human polyomavirus JC (JCV) infection of human B lymphocytes: a possible mechanism for JCV transmigration across the blood-brain barrier. J Infect Dis 202:184–191CrossRefPubMedCentralGoogle Scholar
  41. 41.
    Delbue S, Ferraresso M, Ghio L, Carloni C, Carluccio S, Belingheri M, Edefonti A, Ferrante P (2013) A review on JC virus infection in kidney transplant recipients. Clin Dev Immunol 2013:926391CrossRefPubMedCentralGoogle Scholar
  42. 42.
    Hirsch HH, Babel N, Comoli P, Friman V, Ginevri F, Jardine A, Lautenschlager I, Legendre C, Midtvedt K, Munoz P, Randhawa P, Rinaldo CH, Wieszek A, Hosts ESGoIiC (2014) European perspective on human polyomavirus infection, replication and disease in solid organ transplantation. Clin Microbiol Infect 20(Suppl 7):74–88CrossRefPubMedCentralGoogle Scholar
  43. 43.
    Cheng XS, Bohl DL, Storch GA, Ryschkewitsch C, Gaudreault-Keener M, Major EO, Randhawa P, Hardinger KL, Brennan DC (2011) Inhibitory interactions between BK and JC virus among kidney transplant recipients. J Am Soc Nephrol 22:825–831CrossRefPubMedCentralGoogle Scholar
  44. 44.
    Bodaghi S, Comoli P, Bosch R, Azzi A, Gosert R, Leuenberger D, Ginevri F, Hirsch HH (2009) Antibody responses to recombinant polyomavirus BK large T and VP1 proteins in young kidney transplant patients. J Clin Microbiol 47:2577–2585CrossRefPubMedCentralGoogle Scholar
  45. 45.
    Wunderink HF, van der Meijden E, van der Blij-de Brouwer CS, Mallat MJ, Haasnoot GW, van Zwet EW, Claas EC, de Fijter JW, Kroes AC, Arnold F, Touze A, Claas FH, Rotmans JI, Feltkamp MC (2017) Pretransplantation donor-recipient pair seroreactivity against BK polyomavirus predicts viremia and nephropathy after kidney transplantation. Am J Transplant 17:161–172CrossRefPubMedCentralGoogle Scholar

Copyright information

© IPNA 2018

Authors and Affiliations

  • Britta Höcker
    • 1
    Email author
  • Julia Tabatabai
    • 1
    • 2
    • 3
  • Lukas Schneble
    • 1
  • Jun Oh
    • 4
  • Florian Thiel
    • 4
  • Lars Pape
    • 5
  • Krisztina Rusai
    • 6
  • Rezan Topaloglu
    • 7
  • Birgitta Kranz
    • 8
  • Günter Klaus
    • 9
  • Nikoleta Printza
    • 10
  • Onder Yavascan
    • 11
  • Alexander Fichtner
    • 1
  • Kai Krupka
    • 1
  • Thomas Bruckner
    • 12
  • Rüdiger Waldherr
    • 13
  • Michael Pawlita
    • 14
  • Paul Schnitzler
    • 3
  • Hans H. Hirsch
    • 15
    • 16
  • Burkhard Tönshoff
    • 1
  1. 1.Department of Pediatrics IUniversity Children’s HospitalHeidelbergGermany
  2. 2.German Center for Infection ResearchUniversity Hospital HeidelbergHeidelbergGermany
  3. 3.Department of Infectious Diseases, VirologyUniversity Hospital HeidelbergHeidelbergGermany
  4. 4.Department of Pediatric NephrologyUniversity Children’s HospitalHamburgGermany
  5. 5.Hanover Medical SchoolHanoverGermany
  6. 6.Department of Pediatrics and Adolescent MedicineMedical University ViennaViennaAustria
  7. 7.Faculty of Medicine, Department of Pediatric NephrologyHacettepe UniversityAnkaraTurkey
  8. 8.Department of General PediatricsUniversity Children’s Hospital MünsterMünsterGermany
  9. 9.Department of Pediatric NephrologyUniversity Children’s Hospital MarburgMarburgGermany
  10. 10.1st Pediatric DepartmentAristotle University of ThessalonikiThessalonikiGreece
  11. 11.Department of Pediatric NephrologyTepecik Teaching and Research HospitalİzmirTurkey
  12. 12.Institute of Medical Biometry and InformaticsUniversity of HeidelbergHeidelbergGermany
  13. 13.Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
  14. 14.Division of Molecular Diagnostics of Oncogenic InfectionsGerman Cancer Research CenterHeidelbergGermany
  15. 15.Transplantation & Clinical Virology, Department BiomedicineUniversity of BaselBaselSwitzerland
  16. 16.Infectious Diseases & Hospital EpidemiologyUniversity Hospital BaselBaselSwitzerland

Personalised recommendations