Does this patient have BK virus infection?

BK virus (BKV) is a DNA virus that typically infects children and remains latent in the immunocompetent host.

BK viruria develops in 25% of transplant recipients and viremia in about 15%.

Histologically confirmed Polyoma Virus Allograft Nephropathy (or PVAN) occurs in <5% of patients.

Older age, female donors, HLA DR mismatching and stenting of transplant ureter may be a risk factor for PVAN.

Screening protocols for early detection and prevention of PVAN seem to have better outcomes.

What tests to perform?

• Basic medical panel (BMP): to evaluate renal function.

• Blood and urine BK polymerase chain reaction (PCR) are the favored screening tests.

• Using pathology as the gold standard, blood BKV loads > 16000 copies/mL were 100% sensitive and 96% specific (PPV: 50% and NPV : 100%)

• We recommend following serial Urine PCR tests and when positive also check for serum PCR to estimate burden of disease.

• Urine viral loads > 25 million copies/mL were 100% sensitive and 92% specificity. (PPV: 31% and NPV: 100%)

• Renal biospy to evaluate for clue cells and SV40.

How should patients with BK virus infection be managed?

• Early removal of uretral stents in all renal tranplant patients.

• Serial monitoring of serum PCR is indicated once urine PCR turns positive.

• There is no one effective strategy that is consistently effective.

• For viremia, reduction in intensity of immunosuppression is usually enough to decrease viral loads; drug therapy should only be used once a significant decrease in immunosuppresive therapy is ineffective.

• Although not backed by data, the anti-metabolite component of the regimen is usually reduced or discontinued.

• Cidofovir (dose: GFR dependent) administered intravenously every 2 weeks after IV hydration to minimize the risk of nephrotoxicity.

• Leflunomide started at 100mg/day for 3-5days and then dropped to 20mg/day. Subsequent dosing depends on the 24h trough level of the active metabolite terileflunomide with target levels between 50-100 micrograms/ml noted to be associated with viral clearing and kidney function stabilization.

What happens to patients with polyoma virus allograft nephropathy?

• Patients are at increased risk for allograft dysfunction as well as graft loss.

• PVAN has also been associated with the development of renal cell carcinoma within an allograft as well as metastasis.

How to utilize team care?

• Consult pharmacy for GFR appropriate dosing of antiviral therapy.

• Consider peripherally inserted central catheter (PICC) line placement for prolonged IV therapy.

• Consult Infectious Disease for management of intercurrent infections and advise on invasive disease.

What is the evidence?

Bernhoff, E, Gutteberg, TJ, Sandvik, K, Hirsch, HH, Rinaldo, CH. "Cidofovir inhibits polyomavirus BK replication in human renal tubular cells downstream of viral early gene expression". Am J Transplant,. vol. 8. 2008. pp. 1413-1422.

(This paper describes the use of intravenous cidofovir for mitigating BK virus replication in transplant patients. Caution is indicated with this drug due to its nephrotoxic potential.)

Bohl, DL, Brennan, DC. "BK virus nephropathy and kidney transplantation". Clin J Am Soc Nephrol. vol. 2. 2007. pp. S36-46.

(Nice comprehensive review of BK virus nephropathy and transplantation to include virology, epidemiology, pathology, treatment and outcomes.)

Koukoulaki, M, Grispou, E, Pistolas, D, Balaska, K, Apostolou, T, Anagnostopoulou, M, Tseleni-Kotsovili, A, Hadjiconstantinou, V, Paniara, O, Saroglou, G, Legakis, N, Drakopoulos, S. "Prospective monitoring of BK virus replication in renal transplant recipients". Transpl Infect Dis,. vol. 11. 2009. pp. 1-10.

(This paper examines the impact of prospective screening for BK virus after kidney transplantation and subsequent risk of tissue invasive disase.)

Thomas, A, Dropulic, LK, Rahman, MH, Geetha, D. "Ureteral stents: a novel risk factor for polyomavirus nephropathy". Transplantation,. vol. 84. 2007. pp. 433-436.