Renal Failure in a Kidney Transplant Recipient—BK Virus Nephropathy or Rejection?

Abstract

A 53-year-old Hispanic female received a deceased-donor kidney transplant. Posttransplant, she achieved a baseline serum creatinine of 1.2–1.4 mg/dL. Her maintenance immunosuppression consisted of mycophenolate mofetil 720 mg twice daily, tacrolimus 6 mg twice daily and prednisone 5 mg daily. One-and-a-half years posttransplantation, patient was diagnosed with biopsy-proven BK virus nephropathy (BKVN) with a serum BK virus polymerase chain reaction (PCR) of 135,000 copies/mL. The immunosuppression was reduced (tacrolimus 3 mg twice daily and mycophenolate 360 mg twice daily). Subsequently serum creatinine improved to a baseline of 1.5–1.7 mg/dL and serum BK viremia became undetectable over the next year. She was continued on the lower immunosuppression, and 3 years posttransplantation, patient was admitted with serum creatinine of 2.5 mg/dL. Serum John Cunningham (JC) virus PCR was negative and BK virus PCR was undetectable at <5000 copies/mL. Donor-specific HLA antibodies were negative. The transplant kidney biopsy showed moderate interstitial fibrosis/tubular atrophy with inflammation (Figure 1), focal tubulitis (star, Figure 2) with tubular cells showing slightly enlarged and hyperchromatic nuclei (arrow, Figure 2). No viral cytopathic effects were identified. The stain for polyomavirus showed weak (1 +) nuclear staining (Figure 3). The C4d stain was negative. Acute cellular rejection Banff 1B was diagnosed and patient was treated with high-dose intravenous steroids with improvement in serum creatinine to nadir of 1.8 mg/dL a week later. Subsequently, serum creatinine increased to 3.0 mg/dL a month later. A second transplant biopsy showed persistent inflammation with stronger polyomavirus staining compared to previous biopsy. Serum BK virus PCR was now detectable at 6800 copies/mL.Figure 2:The hematoxylin and eosin stain of transplant kidney biopsy done 3 years posttransplantation shows area of tubulitis (star) and a tubular epithelial cell with an enlarged and hyperchromatic nuclei (arrow). No viral cytopathic effects were seen.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3:The immunohistochemistry of transplant kidney biopsy done 3 years posttransplantation shows a few tubular cells with weak (1 +) stain for polyomavirus.View Large Image Figure ViewerDownload Hi-res image Download (PPT) 1Which of the following statements is true about diagnosis of BKVN?aThe absence of viral cytopathic effects in the transplant kidney biopsy (Figure 2) rules out a diagnosis of BKVN.bThe BK virus inclusion bodies are characteristically present in the cell cytoplasm.cThe onset of serum BK viremia usually coincides with the diagnosis of BKVN.dThe positive and negative predictive value of BK virus PCR for diagnosis of BKVN is reported to be 60% and 100% respectively.eThe detection of immunoglobulin-M (IgM) and the degree of rise of IgM levels may help in diagnosis of BKVN.2The biopsy confirmed polyomavirus nephropathy (PyVAN) may be seen in the absence of detectable serum BK viremia in all of the following conditions except:aJC virus nephropathybAbsence of BK virus–specific T cellscResidual BKVN posttreatmentdInter-laboratory variation in BK virus quantificationeBK virus genotype variance3Which of the following tests may best help distinguish BKVN from acute cellular rejection?aUrinary mRNA for BKV-VP1bUrinary mRNA for granzyme BcUrinary interferon-gamma (IFN-γ)-inducible protein-10dUrine decoy cellsePlasma cell rich inflammation and increased HLA-DR expression on kidney biopsy4The most commonly accepted strategy for treatment of PyVAN is:aReduction in immunosuppressionbLeflunomidecCidofovirdCiproflox acineIntravenous immunoglobulin