BK Virus Nephropathy: Prevalence, Impact and Management Strategies

Figures & data

Figure 1 Monitoring and treatment protocol for BK viremia at our center.

Table 1 Anti-Virals for PVN

Anti-Virals
Name	Class/Mechanism	Dose	Comments
Leflunomide^Citation49^–^Citation52	Anti-Inflammatory; Anti-Viral; Immunosuppressive	PO: Loading- 100 mg daily for 3–5 days; maintenance- 20-60 mg qD; Trough Level −50-100 μg/mL	Can be used following discontinuation of MMF.
Cidofovir^Citation53^–^Citation55	Nucleoside analog	IV: 0.25–1.0 mg/Kg at 1–3 weeks	Used in refractory cases; Nephrotoxicity is the most serious adverse effect.
Brincidofovir^Citation56,Citation57	Investigational Prodrug of Cidofovir; Anti-viral activity	PO: 2 mg/Kg twice weekly	Reasonably well tolerated; Investigational.
Intravenous immunoglobulin (IVIG)^Citation58^–^Citation61	Immunoglobulin preparation with high titers of neutralizing antibodies to BK virus	IV: 0.25–2.0 g/Kg	Can be used as an adjunct to other measures in refractory cases.
Levofloxacin^Citation62^–^Citation64	Fluoroquinolones; Antiviral, inhibit helicase activity of large T antigen	PO: 500 mg qD (renally adjusted)	Levofloxacin failed to show benefit in randomized controlled trials.
Everolimus^Citation47,Citation48	Inhibits mammalian target of rapamycin (mTOR) kinase activity, inhibiting T and B lymphocyte activation and proliferation.	PO 0.75 mg twice daily adjusted to trough levels of 3–8 ng/mL.	Can be used following discontinuation of MMF. Limited literature supporting its use.

Josephson MA, Gillen D, Javaid B, et al. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation. 2006;81(5):704–710. doi:10.1097/01.tp.0000181149.76113.5016534472

 PubMed Web of Science ®Google Scholar

Hirsch HH, Randhawa P. AST infectious diseases community of practice. BK polyomavirus in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):179–188.

 PubMed Web of Science ®Google Scholar

Kadambi PV, Josephson MA, Williams J, et al. Treatment of refractory BK virus-associated nephropathy with cidofovir. Am J Transplant. 2003;3(2):186–191. doi:10.1034/j.1600-6143.2003.30202.x12614296

 PubMed Web of Science ®Google Scholar

Kuypers DR, Vandooren AK, Lerut E, et al. Adjuvant low-dose cidofovir therapy for BK polyomavirus interstitial nephritis in renal transplant recipients. Am J Transplant. 2005;5(8):1997–2004. doi:10.1111/j.1600-6143.2005.00980.x15996251

 PubMed Web of Science ®Google Scholar

Reisman L, Habib S, McClure GB, et al. Treatment of BK virus-associated nephropathy with CMX001 after kidney transplantation in a young child. Pediatr Transplant. 2014;18:E227–E231. doi:10.1111/petr.1234025174393

 PubMed Web of Science ®Google Scholar

Papanicolaou GA, Lee YJ, Young JW, et al. Brincidofovir for polyomavirus-associated nephropathy after allogeneic hema-topoietic stem cell transplantation. Am J Kidney Dis. 2015;65(5):780–784. doi:10.1053/j.ajkd.2014.11.02025600489

 PubMed Web of Science ®Google Scholar

Randhawa P, Pastrana DV, Zeng G, et al. Commercially available immunoglobulins contain virus neutralizing antibodies against all major genotypes of polyomavirus BK. Am J Transplant. 2015;15(4):1014‐1020. doi:10.1111/ajt.13083

 Web of Science ®Google Scholar

Moon J, Chang Y, Shah T, et al. Effects of intravenous immunoglobulin therapy and Fc gamma receptor polymorphisms on BK virus nephropathy in kidney transplant recipients [published online ahead of print, 2020 Apr 23]. Transpl Infect Dis. 2020:e13300. doi:10.1111/tid.13300.32323406

 PubMed Web of Science ®Google Scholar

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(7):1298–1304. doi:10.2215/CJN.0826110920507960

 PubMed Web of Science ®Google Scholar

Knoll GA, Humar A, Fergusson D, et al. Levofloxacin for BK virus prophylaxis following kidney transplantation: a randomized clinical trial. JAMA. 2014;312(20):2106–2114. doi:10.1001/jama.2014.1472125399012

 PubMed Web of Science ®Google Scholar

Bowman LJ, Brueckner AJ, Doligalski CT. The role of mTOR inhibitors in the management of viral infections: a review of current literature. Transplantation. 2018;102:S50–S59. doi:10.1097/TP.000000000000177729369973

 PubMed Web of Science ®Google Scholar

Bussalino E, Marsano L, Parodi A, et al. Everolimus for BKV nephropathy in kidney transplant recipients: a prospective, controlled study. J Nephrol. 2020. doi:10.1007/s40620-020-00777-2

 Web of Science ®Google Scholar