title: Screening Algorithm for BK Virus-Associated Nephropathy Using Sequential Testing of Urinary Cytology: A Probabilistic Model Analysis.
abstract: BACKGROUND
  Incorporating urinary cytology in BK virus (BKV) screening algorithm potentially reduces the screening cost for BK viral nephropathy. We aimed to evaluate the test performances and screening cost of sequential 2-stage screening consisting of urine cytology followed by BKV serum quantitative polymerase chain reaction (PCR).
  
  
  METHODS
  Ninety-five kidney transplant recipients who had BKV serum quantitative PCR/urine cytology tested and verified with histopathology (the reference gold standard) were included. A probabilistic model was constructed to evaluate the test performance and screening cost of 2-stage screening, and was compared with screening with urine cytology or serum viral load alone.
  
  
  RESULTS
  At a viral load threshold of ≥104 copies/ml, the sensitivity and specificity of quantitative PCR alone were 83% (95% CI 69-96) and 91% (95% CI 83-97), respectively. The sensitivity and specificity of urine cytology alone were 91% (95% CI 79-100) and 74% (95% CI 60-91), respectively. Sequential 2-stage screening resulted in loss in sensitivity but a net gain in specificity (viral load threshold ≥104 copies/ml - sensitivity, 75% (95% CI 60-91); specificity, 98% (95% CI 95-99)). Two-stage screening also had superior positive predictive value and is cost effective when BKV-associated nephropathy prevalence is below 94%.
  
  
  CONCLUSIONS
  Our study had demonstrated a favorable test performance and cost efficiency of 2-stage BKV screening.
authors.affiliation: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, SAR, China.
authors.forename: Maggie K M
authors.initials: MK
authors.lastname: Ma
authors.forename: Anskar Y H
authors.initials: AY
authors.lastname: Leung
authors.forename: Kin Yee
authors.initials: KY
authors.lastname: Lo
authors.forename: Weng In
authors.initials: WI
authors.lastname: Lio
authors.forename: Hoi Wong
authors.initials: HW
authors.lastname: Chan
authors.forename: Ivy
authors.initials: I
authors.lastname: Wong
authors.forename: Anthony K C
authors.initials: AK
authors.lastname: Hau
authors.forename: Chun Hay
authors.initials: CH
authors.lastname: Tam
authors.forename: Andrew K M
authors.initials: AK
authors.lastname: Wong
authors.forename: Un I
authors.initials: UI
authors.lastname: Kuok
authors.forename: Ka Foon
authors.initials: KF
authors.lastname: Chau
authors.forename: Samuel K S
authors.initials: SK
authors.lastname: Fung
authors.forename: Tsz Hoi
authors.initials: TH
authors.lastname: Kwan
authors.forename: Sunny S H
authors.initials: SS
authors.lastname: Wong
authors.forename: Sydney C W
authors.initials: SC
authors.lastname: Tang
mesh_terms: D000328:Adult; D000465:Algorithms; D001739:BK Virus; D001706:Biopsy; D020000:Decision Support Systems, Clinical; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis* / Q000652:urine*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D015233:Models, Statistical; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000097:blood / Q000175:diagnosis* / Q000652:urine*; D011237:Predictive Value of Tests; D015995:Prevalence; D011336:Probability; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D066027:Transplant Recipients; D016482:Urinalysis; D019562:Viral Load