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Böbrek transplantasyonu sonrası nefropati ile ilişkili BK virüsü: tek merkez deneyimi

Yıl 2018, Cilt: 10 Sayı: 3, 234 - 239, 30.09.2018
https://doi.org/10.21601/ortadogutipdergisi.376965

Öz

Amaç: BK virüs (BKV) nefropatisi, böbrek transplant alıcılarında allogreft başarısızlığının önemli bir nedeni olup, yüksek derecede potent olan immünsupresif tedaviye bağlıdır. Bu çalışmada BKV viremisi ve BKV ile ilişkili nefropati (BKVN) ile ilişkili risk faktörleri ve tedaviye yanıt da değerlendirildi.

Gereç ve Yöntem: 2008 ve 2014 yılları arasında kadavra kökenli veya canlı ilişkili vericilerden retrospektif olarak 107 renal transplant hastasını analiz ettik. Transplantasyondan sonra, tüm hastalarda vireminin varlığı için BKV polimeraz zincir reaksiyonu (PCR) taraması yaptık. Periferik kan numuneleri ilk üç ayda bir tarama için, daha sonra her üç ayda bir ilk nakil yılının sonuna kadar toplandı. BKV DNA kopyaları gerçek zamanlı PCR ile ölçüldü. Allogreft biyopsileri klinik endikasyona göre yapıldı. Tüm biyopsiler Banff kriterlerine göre analiz edildi ve BKVN varlığı açısından değerlendirildi.

Bulgular: Yüzyedi hastanın 14'ünde (% 13,1) (12 viremi/6 BKVN) BK virüsü ile ilişkili hastalık tespit edildi. BKV ilişkili hastalığı olan (Group I, n:14) ve olmayan hastalar (Group II, n:93) demografik, klinik ve laboratuvar bulgularına göre karşılaştırıldı. BKV ilişkili hastalığı olanlarda serum kreatinin düzeyleri istatistiksel anlamlı olarak daha yüksek bulundu. Ayrıca, yaşlılık ve takrolimus kullanımının BKVN gelişimi için önemli risk faktörleri olduğu saptandı (p <0.05). BKV ile ilişkili hastalığı olanlarda immunsüpresif tedavi dozu azaltıldı ve 1 ay boyunca oral 500 mg/gün levofloksasin kullanıldı. Bu hastalardan greft fonksiyon bozukluğu devam eden üç hastada mikofenolik asit tedavisi durduruldu ve oral 40 mg/gün leflunomid tedavisi eklendi. Leflunomid tedavisi BKV viremisi kaybolup greft fonksiyonu düzelene kadar devam edildi.

Sonuç: BKVN gelişiminde takrolimus kullanımı siklosporinden daha yüksek bir risk ile ilişkilidir. BKVN greft kaybına yol açtığından, BKV replikasyonu için böbrek nakli yapılan hastalar düzenli olarak taranmalıdır. Günümüzde immünsüpresyon dozunun azaltılması en sık görülen tedavi yaklaşımıdır. Ek olarak, leflunomid kullanımı ilave bir tedavi seçeneği gibi gözükmektedir.

 

ğından, BKV replikasyonu için böbrek nakli yapılan hastalar düzenli olarak taranmalıdır. Günümüzde immünsüpresyon dozunun azaltılması en sık görülen tedavi yaklaşımıdır. Buna ek olarak, levofloksasin ve leflunomid kullanımı ilave bir tedavi seçeneği gibi gözükmektedir.

Kaynakça

  • 1. Tan CS, Koralnik IJ. JC, BK, and other polyomaviruses: progressive multifocal leukoencephalopathy. In: Mandell GL, editor. Principles and practices of infectious diseases. 10th ed. Philadelphia: Churchill Livingstone; 2009. 2. Knowles W.A., Pipkin P., Andrews N., Vyse A., Minor P., Brown D.W., et al.(2003) Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40.J.Med.Virol.71:115-123 3. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis, 2003; 3: 611-23. 4. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet, 1971; 1: 1253-57. 5. Mengel M, Marwedel M, Radhermacher J, Eden G, Schwarz A, Haller H, et al. Incidence of polyomavirus nephropathy in renal allografts: influence of modern immunosupressive drugs. Nephrol Dial Transplant, 2003;18:1190-96. 6. Acott P, Babel N. BK virus replication following kidney transplant: Does the choice of immunosupressive regimen influence outcomes? Ann Transplant, 2012;17(1):86-99. 7. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med, 1999;341(23):1725-30. 8. Kalluri HV, Hardinger KL. Current state of renal transplant immunosuppression: Present and future. World J Transplant, 2012; 2(4):51–68. 9. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis, 2003; 3(10): 611–23. 10. Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, et al. Polyomavirus-associated nephropathy in renal transplantation: Interdisciplinary analyses and recommendations. Transplantation, 2005;79(10): 1277–86. 11. Brennan DC, Agha I, Bohl DL, Schnitzler MA, Hardinger KL, Lockwood M, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant, 2005;5(3):582-94. 12. Hirsch HH, Vincenti F, Friman S, 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. Am J Transplant, 2013;13(1): 136-45. 13. 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(7):1019-26. 14. Borni-Duval C, Caillard S, Olagne J, Perrin P, Braun-Parvez L, Heibel F, et al. Risk factors for BK virus infection in the era of therapeutic drug monitoring. Transplantation, 2013 27;95(12):1498-505. 15. Steubl D, Baumann M, Schuster T, Fischereder M, Krämer BK, Heemann U, et al. Risk factors and interventional strategies for BK polyomavirus infection after renal transplantation Scand J Urol Nephrol, 2012;46(6):466-74. 16. Renner FC, Dietrich H, Bulut N, Celik D, Freitag E, Gaertner N, et al. The risk of polyomavirus-associated graft nephropathy is increased by a combined suppression of CD8 and CD4 cell-dependent immune effects. Transplant Proc, 2013 ;45(4):1608-10. 17. Ramos E, Drachenberg CB, Papadimitriou JC, Hamze O, Fink JC, Klassen DK, et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol, 2002;13:2145–51. 18. Schmidt T, Adam C, Hirsch HH, Janssen MWW, Wolf M, Dirks J, et al. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication. Am J Transplant, 2014;14(6):1334-45. 19. Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, et al. Prospective study of Polyomavirus Type BK Replication and nephropathy in renal-transplant recipients. N Engl J Med, 2002; 347:488-96. 20. Schold JD, Rehman S, Kayle LK, Magliocca J, Srinivas TR, Meier‐Kriesche HU. Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States. Transpl Int, 2009;22(6):626-34. 21. Gabardi S, Waikar SS, Martin S, Roberts K, Chen J, Borgi L, et al. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol, 2010;5(7):1298-304. 22. Bernhoff E, Tylden GD, Kjerpeseth LJ, Gutteberg TJ, Hirsch HH, Rinaldo CH. Leflunomide inhibition of BK virus replication in renal tubular epithelial cells. J Virol, 2010;84(4):2150-6. 23. Faguer S, Hirsch HH, Kamar N, Guilbeau‐Frugier C, Ribes D, Guitard J, et al. Leflunomide treatment for polyomavirus BK- associated nephropathy after kidney transplantation. Transpl Int, 2007;20(11):962-9.

BK virus associated nephropathy after renal transplantation: a single center experience

Yıl 2018, Cilt: 10 Sayı: 3, 234 - 239, 30.09.2018
https://doi.org/10.21601/ortadogutipdergisi.376965

Öz




Aim:
BK virus (BKV) nephropathy is an important cause of
allograft failure in renal transplant recipients that is linked to highly
potent immunosuppressive therapy.
The risk factors associated BKV viremia and BKV
associated nephropathy (BKVN) and
response to therapy were also evaluated in this study.



Material and Method: We retrospectively analyzed 107 renal
transplant patients from cadaveric or living related donors between 2008 and
2014.
After
transplantation, w
e performed BKV polymerase chain reaction (PCR) assay screening for the
presence of viremia in all patients.

Peripheral blood samples were collected for screening monthly for first three
months, after then every three months until the end of the first transplant
year.
BKV DNA copies were
measured by real time PCR. Allograft biopsies were performed in the presence of
clinical indication. All biopsies were analyzed according to Banff criteria and
evaluated for the presence of BKVN.



Results: BK virus associated disease was totally detected in 14 patients (13,1%) (12 viremia/6 BKVN) of 107 patients. Demographic, clinical and laboratory findings of BKV-related patients (Group I, n: 14) and non-BKV related patients (Group II, n: 93) were compared. Serum creatinine levels were statistically significantly higher in patients with BKV related disease. Additionally, it was detected that older age and tacrolimus usage are important risk factors for developing BKVN (p< 0.05). In all cases with BKV associated diseases were managed by reducing immunosuppression and, we used oral 500 mg/day levofloxacin for 1 month for all patients. Additionally in three patients with persistent allograft dysfunction following BKVN, the mycophenolic acid was stopped and oral 40 mg/day leflunomide was subsequently started. Leflunomide therapy continued until the BKV viremia disappeared and graft function was improved in the patients 

Conclusion: The use of tacrolimus for BKVN development is associated with a significantly higher risk than cyclosporine. Because BKVN leads to graft loss, renal transplant patients should be screened regularly for BKV replication. Nowadays, reduction of dose immunosuppression is the most common treatment approach. In addition, the use of leflunomide appears to be an additional treatment option.



 



Kaynakça

  • 1. Tan CS, Koralnik IJ. JC, BK, and other polyomaviruses: progressive multifocal leukoencephalopathy. In: Mandell GL, editor. Principles and practices of infectious diseases. 10th ed. Philadelphia: Churchill Livingstone; 2009. 2. Knowles W.A., Pipkin P., Andrews N., Vyse A., Minor P., Brown D.W., et al.(2003) Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40.J.Med.Virol.71:115-123 3. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis, 2003; 3: 611-23. 4. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet, 1971; 1: 1253-57. 5. Mengel M, Marwedel M, Radhermacher J, Eden G, Schwarz A, Haller H, et al. Incidence of polyomavirus nephropathy in renal allografts: influence of modern immunosupressive drugs. Nephrol Dial Transplant, 2003;18:1190-96. 6. Acott P, Babel N. BK virus replication following kidney transplant: Does the choice of immunosupressive regimen influence outcomes? Ann Transplant, 2012;17(1):86-99. 7. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med, 1999;341(23):1725-30. 8. Kalluri HV, Hardinger KL. Current state of renal transplant immunosuppression: Present and future. World J Transplant, 2012; 2(4):51–68. 9. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis, 2003; 3(10): 611–23. 10. Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, et al. Polyomavirus-associated nephropathy in renal transplantation: Interdisciplinary analyses and recommendations. Transplantation, 2005;79(10): 1277–86. 11. Brennan DC, Agha I, Bohl DL, Schnitzler MA, Hardinger KL, Lockwood M, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant, 2005;5(3):582-94. 12. Hirsch HH, Vincenti F, Friman S, 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. Am J Transplant, 2013;13(1): 136-45. 13. 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(7):1019-26. 14. Borni-Duval C, Caillard S, Olagne J, Perrin P, Braun-Parvez L, Heibel F, et al. Risk factors for BK virus infection in the era of therapeutic drug monitoring. Transplantation, 2013 27;95(12):1498-505. 15. Steubl D, Baumann M, Schuster T, Fischereder M, Krämer BK, Heemann U, et al. Risk factors and interventional strategies for BK polyomavirus infection after renal transplantation Scand J Urol Nephrol, 2012;46(6):466-74. 16. Renner FC, Dietrich H, Bulut N, Celik D, Freitag E, Gaertner N, et al. The risk of polyomavirus-associated graft nephropathy is increased by a combined suppression of CD8 and CD4 cell-dependent immune effects. Transplant Proc, 2013 ;45(4):1608-10. 17. Ramos E, Drachenberg CB, Papadimitriou JC, Hamze O, Fink JC, Klassen DK, et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol, 2002;13:2145–51. 18. Schmidt T, Adam C, Hirsch HH, Janssen MWW, Wolf M, Dirks J, et al. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication. Am J Transplant, 2014;14(6):1334-45. 19. Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, et al. Prospective study of Polyomavirus Type BK Replication and nephropathy in renal-transplant recipients. N Engl J Med, 2002; 347:488-96. 20. Schold JD, Rehman S, Kayle LK, Magliocca J, Srinivas TR, Meier‐Kriesche HU. Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States. Transpl Int, 2009;22(6):626-34. 21. Gabardi S, Waikar SS, Martin S, Roberts K, Chen J, Borgi L, et al. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol, 2010;5(7):1298-304. 22. Bernhoff E, Tylden GD, Kjerpeseth LJ, Gutteberg TJ, Hirsch HH, Rinaldo CH. Leflunomide inhibition of BK virus replication in renal tubular epithelial cells. J Virol, 2010;84(4):2150-6. 23. Faguer S, Hirsch HH, Kamar N, Guilbeau‐Frugier C, Ribes D, Guitard J, et al. Leflunomide treatment for polyomavirus BK- associated nephropathy after kidney transplantation. Transpl Int, 2007;20(11):962-9.
Toplam 1 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma makaleleri
Yazarlar

Barış Eser Bu kişi benim 0000-0003-2025-2013

Özlem Yayar Bu kişi benim

Mustafa Şahin 0000-0001-6073-563X

Ünsal Savcı

Başol Canbakan

Mehmet Deniz Aylı Bu kişi benim

Yayımlanma Tarihi 30 Eylül 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 10 Sayı: 3

Kaynak Göster

Vancouver Eser B, Yayar Ö, Şahin M, Savcı Ü, Canbakan B, Aylı MD. BK virus associated nephropathy after renal transplantation: a single center experience. otd. 2018;10(3):234-9.

e-ISSN: 2548-0251

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