title: Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.
abstract: BACKGROUND
  Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction.
  
  
  METHODS
  We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients.
  
  
  RESULTS
  The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results.
  
  
  CONCLUSIONS
  Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.
authors.affiliation: 1 Department of Renal Medicine, Westmead Hospital, NSW, Sydney, Australia. 2 Department of Tissue Pathology and Diagnostic Oncology, Westmead Hospital, NSW, Sydney, Australia. 3 CIDMLS, ICPMR, Sydney, Australia.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nankivell
authors.forename: Jasveen
authors.initials: J
authors.lastname: Renthawa
authors.forename: Neisha
authors.initials: N
authors.lastname: Jeoffreys
authors.forename: Kathy
authors.initials: K
authors.lastname: Kable
authors.forename: Philip J
authors.initials: PJ
authors.lastname: O'Connell
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
authors.forename: Germaine
authors.initials: G
authors.lastname: Wong
authors.forename: Raghwa N
authors.initials: RN
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000952:Antigens, Polyomavirus Transforming / Q000652:urine; D019540:Area Under Curve; D001739:BK Virus / Q000235:genetics / Q000472:pathogenicity*; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D016022:Case-Control Studies; D004279:DNA, Viral / Q000652:urine; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009517:New South Wales / Q000453:epidemiology; D016035:Pancreas Transplantation / Q000009:adverse effects*; D027601:Polyomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine / Q000821:virology; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012372:ROC Curve; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine / Q000821:virology; D016482:Urinalysis / Q000379:methods*; D014552:Urinary Tract Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine / Q000821:virology; D014556:Urine / Q000166:cytology / Q000821:virology; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D000952:Antigens, Polyomavirus Transforming; D015415:Biomarkers; D004279:DNA, Viral