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Biopsy-proven BK virus nephropathy in kidney transplant patients: risk factors, prevalence and treatment approach

Year 2022, Volume: 47 Issue: 4, 1477 - 1484, 28.12.2022
https://doi.org/10.17826/cumj.1133550

Abstract

Purpose: BK virus nephropathy (BKVN) is a latent infection and it is closely associated with immunsuppressive therapy. We aimed in this study to evaluate biopsy-proven BKVN and investigate frequency, risk factors and treatment management.
Materials and Methods: In this study, 422 kidney transplant recipients were analysed retrospectively between April 2014 and April 2020 for biopsy-proven BK virus nephropathy. Group I included 16 kidney transplant patients with biopsy-proven BK nephropathy and group II included 36 kidney transplant patients with negative BK virus nephropathy. We aimed demographic, clinical features of kidney transplant recipients with BKVN (group I, n: 16 ) and non-BKVN (group II, n:36) were compared and the factors affecting of BKVN.
Results: The mean age of grup I and group II were were 41±14.8 years and 39±15.2 respectively. The patients mean follow-up period of 43±11.2 months. Serum creatinine and proteinuria degree were significantly higher in the group with BKVN. In order to reduce the dose of immunosuppression in patients with BKVN, tacrolimus treatment was discontinued in 8 patients, and they were switched to everolimus + MMF + prednisone treatment, leflunamide + MMF + prednisone treatment in 4 patients, and sirolimus + MMF + prednisone treatment in 4 patients. The mean serum creatinine level of the patients who were followed up were observed as 1.78±0.98 mg/dl in group I.
Conclusion: In our center, the prevalance of BKVN was found 3.92% during the study period. Reduction of dose immunosuppressive therapy is the most effective treatment. It is thought that there was no differences between Leflunamide and other approaches for treatment. Early diagnosis and screening (frequently intervals) seems to be most effective way for BKVN.

References

  • 1. Manitpisitkul W, Drachenberg C, Ramos E et al. Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: a case-control study. Transplant 2009; 88(1):83-8.
  • 2. White LH, Casian A, Hilton R et al; Pan-Thames Renal Audit Group. BK virus nephropathy in renal transplant patients in London. Transplantation 2008;85(7):1008-15
  • 3. Tan CS, Koralnik JC. BK, and other polyomaviruses: progressive multifocal leukoencephalopathy. In: Mandell GL, editor. Principles and practices of infectious diseases. 10th ed. Philadelphia: Churchill Livingstone; 2009.
  • 4. Knowles WA, Pipkin P, Andrews N. Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 2003; 71:115-23.
  • 5. Mengel M, Marwedel M, Radhermacher J. Incidence of polyomavirus nephropathy in renal allografts: influence of modern immunosupressive drugs. Nephrol Dial Transplant 2003;18:1190-6.
  • 6. Nickeleit V, Hirsch HH, Zeiler M et al. BK virus nephropathy in renal transplant-tubular necrosis, MHC class II expression and rejection in a puzzling game. Nephrol Dial Transplant 2000; 15:324.
  • 7. Hirsch HH, Brennan DC, Drachenberg CB et al. Polyomavirus associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 2005; 79: 1277.
  • 8. Wiseman AC. Polyomavirus Nephropathy: a current perspective and clinical considerations, Am J Kidney Dis, 2009, vol. 54 (pg. 131-142)
  • 9. Sachdeva MS, Nada R, Jha V et al. The high incidence of BK polyoma virus infection among renal transplant recipient in India. Transplantation. 2004; 77: 429.
  • 10. Awadalla Y, Randhawa P, Ruppert K et al. HLA mismatching increases the risk of BK virus nephropathy in renal transplant recipients. Am J Transplant 2004; 4: 1691.
  • 11. Trofe J, Gaber LW, Stratta RJ et al. Polyomavirus in kidney and kidney-pancreas transplant recipients. Transpl Infect Dis 2003; 5: 21-28.
  • 12. Brennan DC, Agha I, Bohl DL. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005;5:582-94.
  • 13. Hirsch HH, Vincenti F, Friman S. Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study. Am J Transplant 2013;13: 136-45. 13.
  • 14. Dharnidharka VR, Cherikh WS, Abbott KC. An OPTN analysis of national registry data on treatment of BK virus allograft nephropathy in the United States. Transplantation 2009;15:87:1019-26.
  • 15. Steubl D, Baumann M, Schuster T. Risk factors and interventional strategies for BK polyomavirus infection after renal transplantation Scand J Urol Nephrol 2012;46:466-74.
  • 16. Randhawa P, Brennan DC. BK virus infection in transplant recipients: an overview and update. Am J Transplant 2006;6(9):2000-5. 20.
  • 17. Mischitelli M, Bellizzi A, Anzivino E et al. Complications post renal transplantation: literature focus on BK virus nephropathy and diagnostic tools actually available. Virol J 2008;5:38
  • 18. Josephson MA, Gillen D, Javaid B et al. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplant 2006;81(5):704-10.
  • 19. Johnston O, Jaswal D, Gill JS. Treatment of polyomavirus infection in kidney transplant recipients: a systematic review. Transplantation 2010; 89: 1057–1070.
  • 20. Lee BT, Gabardi S, Grafals M. Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebocontrolled trial. Clin J Am Soc Nephrol 2014; 9: 583–589.
  • 21. Gabardi S, Waikar SS, Martin S. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol 2010;5: 1298-304.
  • 22. Hashim F, Rehman S, Gregg JA et al. Ureteral Stent Placement Increases the Risk for Developing BK Viremia after Kidney Transplantation. J Transplant. 2014;2014:459747.
  • 23. Atencio IA, Shadan FF, Zhou XJ et al. Adult mouse kidneys become permissive to acute polyomavirus infection and reactivate persistent infections in response to cellular damage and regeneration. J Virol. 1993;67: 1424–32.
  • 24. Atencio IA, Villarreal LP. Polyomavirus replicates in differentiating but not in proliferating tubules of adult mouse polycystic kidneys. Virology. 1994; 201: 26–35.
  • 25. Kayler L, Zendejas I, Schain D et al. Ureteral stent placement and BK viremia in kidney transplant recipients. Transpl Infect Dis. 2013; 15: 202–7.

Böbrek nakli hastalarında biyopsi ile kanıtlanmış BK virüs nefropatisi: risk faktörleri, sıklığı ve tedavi yaklaşımı

Year 2022, Volume: 47 Issue: 4, 1477 - 1484, 28.12.2022
https://doi.org/10.17826/cumj.1133550

Abstract

Amaç: BK virüs nefropatisi (BKVN) böbrek nakli sonrasında immunsupresif tedavi dozu ile yakından ilişkili, latent enfeksiyonun reaktivasyonudur. Bu çalışmada kliniğimizde takipli hastalarda BKVN sıklığını ve olası risk faktörlerini değerlendirmeyi amaçladık.
Gereç ve Yöntem: Nisan 2014- Nisan 2020 tarihleri arasında kliniğimizden takipli olan 422 böbrek nakil hastası BK virus nefropati açısından geriye dönük oalrak analiz edildi. Gruo I’e biyopsi ile kanıtlanmış BK virus nefroatili 16 hasta, grup II’ye ise BK virus negatif olan 36 hasta dahil edildi. BKVN saptanan 16 hastanın (grup I) ve BKVN negatif olan 36 hastanın (grup II) demografik, klinik ve laboratuar özellikleri özellikleri ile BKVN ilişkili faktörler karşılaştırıldı.
Bulgular: Grup I’deki hastaların yaş ortalaması 41±14.8 yıl, grup II’deki hastaların yaş ortalaması ise 39±15.2 yıl olarak saptandı. Hastaların böbrek nakli sonrasında ortalama takip süreleri 43±11.2 ay idi. BKVN olan grupta serum kreatinin ve proteinüri düzeyinin istatistiksel anlamlı olarak daha yüksek olduğu saptandı. BKVN saptanan hastalarda immunsupresyon dozunu azaltmak amacı ile 8 hastada kullanmakta oldukları takrolimus tedavisi kesilerek everolimus +MMF+ prednisone tedavisine, 4 hastada leflunamid+ MMF+ prednisone tedavisine, 4 hastada ise sirolimus +MMF+ prednisone tedavisine geçiş yapıldı. BKVN tanısı sonrasında hastaların ortalama 58.9±34.2 ay takip edildiği, 1 hastada NODAT geliştiği, 2 hastanın kardiyovasküler nedenlerle kaybedildiği, 2 hastanın ise greft kaybı nedeni ile hemodiyaliz tedavisine döndüğü gözlendi. Takibe devam eden hastaların ortalama serum kreatinin değerlerinin 1.78±0.98 mg/dl olarak gözlendi.
Sonuç: Kliniğimizde çalışmanın yapıldığı dönemde BKVN sıklığı %4.86 olarak gözlendi. İmmunsupresif tedavi dozunun azaltılması hala en etkin tedavi yöntemidir. Leflunamid tedavisi ile diğer tedavi yaklaşımları arasında fark olmadığı saptandı. Sık aralıklarla tarama ve erken tanının BKVN takibinde daha etkili olduğu gözlenmiştir.

References

  • 1. Manitpisitkul W, Drachenberg C, Ramos E et al. Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: a case-control study. Transplant 2009; 88(1):83-8.
  • 2. White LH, Casian A, Hilton R et al; Pan-Thames Renal Audit Group. BK virus nephropathy in renal transplant patients in London. Transplantation 2008;85(7):1008-15
  • 3. Tan CS, Koralnik JC. BK, and other polyomaviruses: progressive multifocal leukoencephalopathy. In: Mandell GL, editor. Principles and practices of infectious diseases. 10th ed. Philadelphia: Churchill Livingstone; 2009.
  • 4. Knowles WA, Pipkin P, Andrews N. Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 2003; 71:115-23.
  • 5. Mengel M, Marwedel M, Radhermacher J. Incidence of polyomavirus nephropathy in renal allografts: influence of modern immunosupressive drugs. Nephrol Dial Transplant 2003;18:1190-6.
  • 6. Nickeleit V, Hirsch HH, Zeiler M et al. BK virus nephropathy in renal transplant-tubular necrosis, MHC class II expression and rejection in a puzzling game. Nephrol Dial Transplant 2000; 15:324.
  • 7. Hirsch HH, Brennan DC, Drachenberg CB et al. Polyomavirus associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 2005; 79: 1277.
  • 8. Wiseman AC. Polyomavirus Nephropathy: a current perspective and clinical considerations, Am J Kidney Dis, 2009, vol. 54 (pg. 131-142)
  • 9. Sachdeva MS, Nada R, Jha V et al. The high incidence of BK polyoma virus infection among renal transplant recipient in India. Transplantation. 2004; 77: 429.
  • 10. Awadalla Y, Randhawa P, Ruppert K et al. HLA mismatching increases the risk of BK virus nephropathy in renal transplant recipients. Am J Transplant 2004; 4: 1691.
  • 11. Trofe J, Gaber LW, Stratta RJ et al. Polyomavirus in kidney and kidney-pancreas transplant recipients. Transpl Infect Dis 2003; 5: 21-28.
  • 12. Brennan DC, Agha I, Bohl DL. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005;5:582-94.
  • 13. Hirsch HH, Vincenti F, Friman S. Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study. Am J Transplant 2013;13: 136-45. 13.
  • 14. Dharnidharka VR, Cherikh WS, Abbott KC. An OPTN analysis of national registry data on treatment of BK virus allograft nephropathy in the United States. Transplantation 2009;15:87:1019-26.
  • 15. Steubl D, Baumann M, Schuster T. Risk factors and interventional strategies for BK polyomavirus infection after renal transplantation Scand J Urol Nephrol 2012;46:466-74.
  • 16. Randhawa P, Brennan DC. BK virus infection in transplant recipients: an overview and update. Am J Transplant 2006;6(9):2000-5. 20.
  • 17. Mischitelli M, Bellizzi A, Anzivino E et al. Complications post renal transplantation: literature focus on BK virus nephropathy and diagnostic tools actually available. Virol J 2008;5:38
  • 18. Josephson MA, Gillen D, Javaid B et al. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplant 2006;81(5):704-10.
  • 19. Johnston O, Jaswal D, Gill JS. Treatment of polyomavirus infection in kidney transplant recipients: a systematic review. Transplantation 2010; 89: 1057–1070.
  • 20. Lee BT, Gabardi S, Grafals M. Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebocontrolled trial. Clin J Am Soc Nephrol 2014; 9: 583–589.
  • 21. Gabardi S, Waikar SS, Martin S. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol 2010;5: 1298-304.
  • 22. Hashim F, Rehman S, Gregg JA et al. Ureteral Stent Placement Increases the Risk for Developing BK Viremia after Kidney Transplantation. J Transplant. 2014;2014:459747.
  • 23. Atencio IA, Shadan FF, Zhou XJ et al. Adult mouse kidneys become permissive to acute polyomavirus infection and reactivate persistent infections in response to cellular damage and regeneration. J Virol. 1993;67: 1424–32.
  • 24. Atencio IA, Villarreal LP. Polyomavirus replicates in differentiating but not in proliferating tubules of adult mouse polycystic kidneys. Virology. 1994; 201: 26–35.
  • 25. Kayler L, Zendejas I, Schain D et al. Ureteral stent placement and BK viremia in kidney transplant recipients. Transpl Infect Dis. 2013; 15: 202–7.
There are 25 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Eda Altun 0000-0002-5564-356X

Sena Ulu 0000-0003-0085-2193

Süheyla Apaydın 0000-0001-6224-405X

Bahtışen Güven 0000-0002-8455-9383

Publication Date December 28, 2022
Acceptance Date September 23, 2022
Published in Issue Year 2022 Volume: 47 Issue: 4

Cite

MLA Altun, Eda et al. “Biopsy-Proven BK Virus Nephropathy in Kidney Transplant Patients: Risk Factors, Prevalence and Treatment Approach”. Cukurova Medical Journal, vol. 47, no. 4, 2022, pp. 1477-84, doi:10.17826/cumj.1133550.