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

Baris Eser; Ozlem Yayar; Mustafa Sahin; Unsal Savci; Basol Canbakan; Mehmet Deniz Ayli

doi:10.21601/ortadogutipdergisi.376965

ORTADOĞU TIP DERGİSİ - ORTADOGU MEDICAL JOURNAL

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

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

Baris Eser ¹, Ozlem Yayar ², Mustafa Sahin ³ ^* , Unsal Savci ⁴, Basol Canbakan ⁵, Mehmet Deniz Ayli ⁵

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Ortadogu Tıp Derg, Volume 10, Issue 3, pp. 234-239

https://doi.org/10.21601/ortadogutipdergisi.376965

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Abstract

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, we 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.

Keywords: BK virus, renal transplantation, nephropathy

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.

Keywords: BK virüsü, renal transplantasyon, nefropati

References

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.
Knowles WA, Pipkin P, Andrews N, et al. Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 2003; 71:115-23.
Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis 2003; 3: 611-23.
Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet 1971; 1: 1253-57.
Mengel M, Marwedel M, Radhermacher J, et al. Incidence of polyomavirus nephropathy in renal allografts: influence of modern immunosupressive drugs. Nephrol Dial Transplant 2003;18:1190-6.
Acott P, Babel N. BK virus replication following kidney transplant: Does the choice of immunosupressive regimen influence outcomes? Ann Transplant 2012;17:86-99.
Wolfe RA, Ashby VB, Milford EL, 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;341:1725-30.
Kalluri HV, Hardinger KL. Current state of renal transplant immunosuppression: Present and future. World J Transplant 2012; 2:51–68.
Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis 2003; 3: 611–23.
Hirsch HH, Brennan DC, Drachenberg CB, et al. Polyomavirus-associated nephropathy in renal transplantation: Interdisciplinary analyses and recommendations. Transplantation 2005;79: 1277–86.
Brennan DC, Agha I, Bohl DL, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005;5:582-94.
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: 136-45.
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.
Borni-Duval C, Caillard S, Olagne J, et al. Risk factors for BK virus infection in the era of therapeutic drug monitoring. Transplantation 2013 27;95:1498-505.
Steubl D, Baumann M, Schuster T, et al. Risk factors and interventional strategies for BK polyomavirus infection after renal transplantation Scand J Urol Nephrol 2012;46:466-74.
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 ;45:1608-10.
Ramos E, Drachenberg CB, Papadimitriou JC, et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol 2002;13:2145–51.
Schmidt T, Adam C, Hirsch HH, et al. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication. Am J Transplant 2014;14:1334-45.
Hirsch HH, Knowles W, Dickenmann M, et al. Prospective study of Polyomavirus Type BK Replication and nephropathy in renal-transplant recipients. N Engl J Med 2002; 347:488-96.
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; 22:626-34.
Gabardi S, Waikar SS, Martin S, et al. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol 2010;5: 1298-304.
Min D, Vu D, Kawewat B, et al. Effect of ciprofloxacin prophylaxis on BK virus infection after renal transplantation. Am J Transplant 2013;13: 434 [Abstract].
Eng M, Jones C, Marvin M. Fluoroquinolone prophylaxis is ineffective in preventing BK polyoma viremia after renal transplant. Transplantation 2014; 98: 86 [Abstract].
C- Song TR, Rao ZS, Qiu Y, et al. Fluoroquinolone prophylaxis in preventing BK polyomavirus infection after renal transplant: A systematic review and meta-analysis. Kaohsiung J Med Sci 2016 Mar;32: 152-9.
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;84:2150-6.
Faguer S, Hirsch HH, Kamar N, et al. Leflunomide treatment for polyomavirus BK- associated nephropathy after kidney transplantation. Transpl Int 2007;20):962-9.

Citation

Eser B, Yayar O, Sahin M, Savci U, Canbakan B, Ayli MD. BK virus associated nephropathy after renal transplantation: a single center experience. Ortadogu Tıp Derg. 2018;10(3):234-9. https://doi.org/10.21601/ortadogutipdergisi.376965

Eser, B., Yayar, O., Sahin, M., Savci, U., Canbakan, B., & Ayli, M. D. (2018). BK virus associated nephropathy after renal transplantation: a single center experience. Ortadoğu Tıp Dergisi, 10(3), 234-239. https://doi.org/10.21601/ortadogutipdergisi.376965

Eser, B., Yayar, O., Sahin, M., Savci, U., Canbakan, B., and Ayli, M. D. (2018). BK virus associated nephropathy after renal transplantation: a single center experience. Ortadoğu Tıp Dergisi, 10(3), pp. 234-239. https://doi.org/10.21601/ortadogutipdergisi.376965

Eser B, Yayar O, Sahin M, Savci U, Canbakan B, Ayli MD. BK virus associated nephropathy after renal transplantation: a single center experience. Ortadogu Tıp Derg. 2018;10(3), 234-239. https://doi.org/10.21601/ortadogutipdergisi.376965

Eser, Baris, Ozlem Yayar, Mustafa Sahin, Unsal Savci, Basol Canbakan, and Mehmet Deniz Ayli. "BK virus associated nephropathy after renal transplantation: a single center experience". Ortadoğu Tıp Dergisi 2018 10 no. 3 (2018): 234-239. https://doi.org/10.21601/ortadogutipdergisi.376965

Eser, Baris et al. "BK virus associated nephropathy after renal transplantation: a single center experience". Ortadoğu Tıp Dergisi, vol. 10, no. 3, 2018, pp. 234-239. https://doi.org/10.21601/ortadogutipdergisi.376965