Slideshow
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Slide 1
Representative micrographs of biopsied renal allograft tissue.
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Slide 2
Representative micrographs of biopsied renal allograft tissue.
A Caucasian woman in her 20s was admitted for acute kidney injury. She had a living-related renal transplant from her mother about 18 months previously with a nadir creatinine of 1 mg/day.
Her prior end-stage renal disease was attributed to chronic reflux nephropathy. About 2 weeks previously, she developed nausea, decreased oral intake, and loose bowel movement. Her serum creatinine increased to 2.5 mg/dL. She went to the emergency room, where she received a presumptive diagnosis of gastroenteritis. Her symptoms improved with supportive care and creatinine declined after intravenous sodium chloride infusion.
At her current presentation, the physical exam was unremarkable. Urinalysis reveals no protein, 1 RBC and 3 WBC. CBC is unremarkable. Serum creatinine rose to 1.6 mg/dL. Ultrasound examination revealed no obstruction; Doppler revealed no significant findings. Tacrolimus trough was 5. A biopsy of the allograft was performed. Shown here are representative micrographs.
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The representative micrographs show viral inclusions with positive SV40 stain consistent with BK nephropathy. Serum BK PCR levels exceeded 400,000 copies. The allograft biopsy also demonstrates interstitial infiltrate and some evidence of tubulitis with lymphocytic infiltration.
The differential diagnosis of tubulitis in this case includes acute cellular rejection, infection, and acute interstitial/allergic nephritis. The finding of viral inclusions in the regions of tubulitis leads to the diagnosis of a viral nephropathy.
Preemptive screening of urine and/or blood for polyoma virus is employed by many transplant centers during the first post-transplant year. Once detected, the main treatment of BK viremia and nephropathy is reduction of immunosuppression. The first step involves dose reduction/cessation of the anti-metabolite agent. Viral PCR counts should be followed to confirm reduction in viral load.
Adjunctive antiviral treatments for BK nephropathy include quinolone antibiotics, leflunomide, cidofovir, and IVIg. Quinolone agents such as ciprofloxacin and levofloxacin act against polyoma virus infection by actions involving alterations in DNA topoisomerase and helicase activity. Various observational studies have reported that administration of quinolones leads to decreased BK PCR serum levels.
A recent small randomized, controlled trial that compared levofloxacin to placebo was unable to demonstrate any statistically significant reduction of serum BK viral counts in patients who received the drug. Nonetheless, many specialists will still consider quinolone use in patients with BK nephropathy. Transplant patients who receive quinolone therapy in such cases should be aware of the potential risk for tendonitis, a potential adverse event that seems to be more pronounced in the transplant population.
Leflunamide is a drug with anti-inflammatory and antiviral properties frequently prescribed for BK nephropathy. It is used to treat rheumatoid arthritis. Drug levels can be followed. Adverse effects include pancytopenias, and potential severe rash.
Intravenous immunoglobulin has been used in transplant patients with BK nephropathy in conjunction with reduction of immunosuppressive regimen, as noted above. No randomized controlled trials have been done to demonstrate significant benefit of this agent separate from reduction of immunosuppression.
The patient in this case had immunosuppression medications reduced and her BK PCR levelsfollowed. Remission of viral counts to a minimal level eventually required administration of leflunamide and subsequently ciprofloxacin. Her GFR eventually stabilized with control of viremia.
Answer: Decrease/stop mycophenolate
This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine, Division of Nephrology & Hypertension, and Philip Carpenter, MD, Professor of Clinical Pathology at the University of California in Irvine.
References
- Dall A, Hariharan S. BK virus nephritis after renal transplantation. Clin J Am Soc Nephrol 2008;3 Suppl 2:S68-S75
- Johnston O, Jaswal D, Gill JS, et al. Treatment of polyomavirus infection in kidney transplant recipients: a systematic review. Transplantation 2010;89:1057-1070.
- Lee BT, Gabardi S, Grafals M, et al. Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebo-controlled trial. Clin J Am Soc Nephrol 2014;9:583-589
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