Zusammenfassung
Hintergrund
Die BK-Polyomavirus(BKPyV)-Reaktivierung nach Nierentransplantation führt bei bis zu 10 % der transplantierten Patienten zu einer polyomavirusassoziierten Nephropathie (PyVAN), von denen bis zu 50 % einen Transplantatverlust erleiden. Der Hauptrisikofaktor der BKPyV-Reaktivierung ist die immunsuppressive Therapie durch einerseits die immunsuppressive Wirkung und andererseits direkte medikamentenabhängige Effekte auf die Virusreplikation. Bis heute existiert keine kausale Therapie der PyVAN.
Ziel
Diese Übersichtsarbeit soll die aktuellen diagnostischen und therapeutischen Empfehlungen bei BKPyV-Reaktivierung nach Nierentransplantation darstellen.
Schlussfolgerung
Ein sorgfältiges Screening nach Nierentransplantation auf BKPyV eröffnet die Möglichkeit einer in Abhängigkeit von der Viruslast stehenden frühzeitigen Anpassung der Immunsuppression. Durch die frühzeitige Anpassung der Immunsuppression kann ein Fortschreiten der PyVAN verhindert werden und die Transplantatfunktion erhalten bleiben.
Abstract
Background
Reactivation of the BK polyomavirus(BKPyV) leads to polyomavirus-associated nephropathy (PyVAN) in up to 10 % of renal transplantion patients and is associated with transplant failure in up to 50 %. The main risk factor for BKPyV reactivation is immunosuppressive therapy due to its immunosuppressive effect and drug-dependent influence on virus replication. So far there is no antiviral causal therapy for PyVAN.
Aim
This review article discusses the current diagnostic steps and therapies recommended for BKPyV reactivation after renal transplantation.
Conclusion
The possibility for early intervention and prevention of PyVAN progression depends on a thorough screening for BKPyV replication after renal transplantation. Transplant function can be preserved and progression of viral replication can be prevented by early adjustment of the immunosuppressive therapy determined by the viral load.
Literatur
Antonsson A, Green AC, Mallitt K‑A et al (2010) Prevalence and stability of antibodies to the BK and JC polyomaviruses: A long-term longitudinal study of Australians. J Gen Virol 91:1849–1853. doi:10.1099/vir.0.020115-0
Blyth E, Clancy L, Simms R et al (2011) BK virus-specific T cells for use in cellular therapy show specificity to multiple antigens and polyfunctional cytokine responses. Transplantation 92:1077–1084. doi:10.1097/TP.0b013e31823328c0
Borni-Duval C, Caillard S, Olagne J et al (2013) Risk factors for BK virus infection in the era of therapeutic drug monitoring. Transplantation 95(12):1498–1505. doi:10.1097/TP.0b013e3182921995
Comoli P (2003) Dendritic cells pulsed with polyomavirus BK antigen induce ex vivo polyoma BK virus-specific cytotoxic T‑cell lines in seropositive healthy individuals and renal transplant recipients. J Am Soc Nephrol 14:3197–3204. doi:10.1097/01.ASN.0000096374.08473.E3
Dadhania D, Snopkowski C, Ding R et al (2008) Epidemiology of BK virus in renal allograft recipients: Independent risk factors for BK virus replication. Transplantation 86:521–528. doi:10.1097/TP.0b013e31817c6447
Dekeyser M, François H, Beaudreuil S, Durrbach A (2015) Polyomavirus-specific cellular immunity: from BK-virus-specific cellular immunity to BK-virus-associated nephropathy? Front Immunol 6:307. doi:10.3389/fimmu.2015.00307
Drachenberg CB, Papadimitriou JC, Hirsch HH et al (2004) Histological patterns of polyomavirus nephropathy: Correlation with graft outcome and viral load. Am J Transplant 4:2082–2092. doi:10.1046/j.1600-6143.2004.00603.x
Eash S, Manley K, Gasparovic M et al (2006) The human polyomaviruses. Cell Mol Life Sci 63:865–876. doi:10.1007/s00018-005-5454-z
Egli A, Infanti L, Dumoulin A et al (2009) Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 199:837–846. doi:10.1086/597126
Gard L, Niesters HGM, Riezebos-Brilman A (2015) A real time genotyping PCR assay for polyomavirus BK. J Virol Methods 221:51–56. doi:10.1016/j.jviromet.2015.04.024
Gosert R, Rinaldo CH, Funk GA et al (2008) Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology. J Exp Med 205:841–852. doi:10.1084/jem.20072097
Hirsch HH, Babel N, Comoli P et al (2014) European perspective on human polyomavirus infection, replication and disease in solid organ transplantation. Clin Microbiol Infect 20(Suppl 7):74–88. doi:10.1111/1469-0691.12538
Hirsch HH, Brennan DC, Drachenberg CB et al (2005) Polyomavirus-associated nephropathy in renal transplantation: Interdisciplinary analyses and recommendations. Transplantation 79:1277–1286
Hirsch HH, Knowles W, Dickenmann M et al (2002) Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med 347:488–496. doi:10.1056/NEJMoa020439
Hirsch HH, Randhawa P (2013) BK polyomavirus in solid organ transplantation. Am J Transplant 13:179–188. doi:10.1111/ajt.12110
Hirsch HH, Yakhontova K, Lu M, Manzetti J (2016) BK polyomavirus replication in renal tubular epithelial cells is inhibited by sirolimus, but activated by tacrolimus through a pathway involving FKBP-12. Am J Transplant 16(3):821–832. doi:10.1111/ajt.13541
Jin L, Gibson PE, Booth JC, Clewley JP (1993) Genomic typing of BK virus in clinical specimens by direct sequencing of polymerase chain reaction products. J Med Virol 41:11–17
Jouve T, Rostaing L, Malvezzi P (2016) Place of mTOR inhibitors in management of BKV infection after kidney transplantation. J Nephropathol 5:1–7. doi:10.15171/jnp.2016.01
Kasiske BL, Zeier MG, Chapman JR et al (2010) KDIGO clinical practice guideline for the care of kidney transplant recipients: A summary. Kidney Int 77:299–311. doi:10.1038/ki.2009.377
Lee HM, Jang I‑A, Lee D et al (2015) Risk factors in the progression of BK virus-associated nephropathy in renal transplant recipients. Korean J Intern Med 30:865–872. doi:10.3904/kjim.2015.30.6.865
Moscarelli L, Caroti L, Antognoli G et al (2013) Everolimus leads to a lower risk of BKV viremia than mycophenolic acid in de novo renal transplantation patients: A single-center experience. Clin Transplant 27:546–554. doi:10.1111/ctr.12151
Nankivell BJ, Renthawa J, Jeoffreys N et al (2015) Clinical utility of urinary cytology to detect BK viral nephropathy. Transplantation 99:1715–1722. doi:10.1097/TP.0000000000000642
Nickeleit V, Klimkait T, Binet IF et al (2000) Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. N Engl J Med 342:1309–1315. doi:10.1056/NEJM200005043421802
Ramos E, Drachenberg CB, Wali R, Hirsch HH (2009) The decade of polyomavirus BK-associated nephropathy: state of affairs. Transplantation 87:621–630. doi:10.1097/TP.0b013e318197c17d
Sachdeva MS, Nada R, Jha V et al (2004) The high incidence of BK polyoma virus infection among renal transplant recipients in India. Transplantation 77:429–431. doi:10.1097/01.TP.0000113163.02039.30
Schachtner T, Babel N, Reinke P (2015) Different risk factor profiles distinguish early-onset from late-onset BKV-replication. Transpl Int 28:1081–1091. doi:10.1111/tri.12601
Singh HK, Reisner H, Derebail VK et al (2015) Polyomavirus nephropathy: Quantitative urinary polyomavirus-Haufen testing accurately predicts the degree of intrarenal viral disease. Transplantation 99:609–615. doi:10.1097/TP.0000000000000367
Thangaraju S, Gill J, Wright A et al (2016) Risk factors for BK polyoma virus treatment and association of treatment with kidney transplant failure: Insights from a paired kidney analysis. Transplantation 100:854–861. doi:10.1097/TP.0000000000000890
Trydzenskaya H, Sattler A, Müller K et al (2011) Novel approach for improved assessment of phenotypic and functional characteristics of BKV-specific T‑cell immunity. Transplantation 92:1269–1277. doi:10.1097/TP.0b013e318234e0e5
Vu D, Shah T, Ansari J et al (2015) Efficacy of intravenous immunoglobulin in the treatment of persistent BK viremia and BK virus nephropathy in renal transplant recipients. Transplant Proc 47:394–398. doi:10.1016/j.transproceed.2015.01.012
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O. Witzke hat Forschungsstipendien für klinische Studien, Vergütungen für Reden, Honorare und Reisekostenerstattungen von Alexion, Amgen, Astellas, Bristol-Myers Squibb, Chiesi, Novartis, Roche, Pfizer und Sanofi erhalten. J. Verheyen erhielt Honorare und Reisekostenerstattungen von GlaxoSmithKline GmbH & Co. KG. J. Korth erhielt Reisekostenunterstützungen von Astellas und Roche.
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U. Heemann, München
O. Witzke, Essen
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Korth, J., Verheyen, J. & Witzke, O. BK-Polyomavirus-Reaktivierung nach Nierentransplantation. Nephrologe 11, 402–407 (2016). https://doi.org/10.1007/s11560-016-0095-9
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DOI: https://doi.org/10.1007/s11560-016-0095-9
Schlüsselwörter
- BK-Polyomavirus
- Screeningalgorithmus
- Polyomavirusassoziierte Nephropathie
- Reduktion der Immunsuppression
- BKV-spezifische T‑Zell-Antwort