POLYOMAVIRUS INFECTION IN RENAL ALLOGRAFTS: PROGRESS SINCE BANFF 1999

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POLYOMAVIRUS INFECTION IN RENAL ALLOGRAFTS
PROGRESS SINCE BANFF 1999

• Parmjeet Randhawa
• Associate Professor
• Division of Transplantation Pathology
• Department of Pathology
• University of Pittsburgh

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SCOPE OF PROGRESS

• BKV infection
• JCV infection
• SV40 infection

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MORPHOLOGIC SPECTRUM OF BKVN

• Silent viral inclusions
• Acute tubular necrosis
• Viral interstitial nephritis
• Basel group believes in concurrent rejection

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SIGNIFICANCE OF INTERSTITIAL INFLAMM TUBULITIS
IN BKVAN

• Morphology can not distinguish response to
• viral ags (VIN), from allogeneic ags (ACR)
• Experience with CMV suggests
• relationship between viral infection
• rejection is bidirectional
• - Therapy of rejection can activate virus
• - Reduced immunosuppression after diagnosis
• of BKVAN can precipitate rejection
• It is possible to have 2 diagnoses in 1 biopsy

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THERAPEUTIC CONSIDERATIONS IN BKVAN

• Most centers reduce immunosuppression
• Basel group feels steroids indicated in cases
  with concurrent rejection but they also reduce
  immsup later (n5)
• Pittsburgh finds worse prognosis if steroids
  given 58 graft loss (n12) vs 10 (n18)
• Anti-viral drugs are being tried empirically

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MONITORING BKV LOAD IN CLINICAL SPECIMENS

• APPLICATIONS
• Early diagnosis before significant graft injury
• Possibility of pre-emptive Rx
• Titration of dose of FK506 duration of
  antiviral drugs in cases of established BKVAN

• TECHNIQUES

• Urine cytology
• Urinary PCR
• Blood PCR

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URINE CYTOLOGY

• Baltimore group finds urinary inclusions to have
  90 predictive value for BKVAN
• Basel finds positive predictive value to be much
  lower (30), but uses it to screen high risk
  patients (FK506, MMF, rejection)
• Two samples gt5 decoy cells/10hpf trigger plasma
  PCR positive PCR triggers biopsy

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UTILITY OF PLASMA PCR IN DIAGNOSIS OF BKVAN AT
BASEL

• Plasma PCR positive in 11/11 BKVAN
• Undetectable after clinical response
• Asymptomatic patients plasma PCR in 1/25
  without 1/16 patients with decoy cells in urine

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QUANTITATIVE PCR IN URINE SAMPLES FROM PTS WITH
BKVAN(VATS ET AL, PITTSBURGH)

• 16 patients with BKVAN urinary viral load 10,000
  - 100,000 copies /microgram of creatinine
• Lowering of immunosuppression produced variable
  decrease in viral load
• Antiviral therapy resulted in clearance of
  viruria in 5 patients

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JCV INFECTION IN RENAL ALLOGRAFTS

• JCV coinfection in 7/19 (36) of bx with BKVN
• No JCV found in 19 control biopsies suggesting
• JCV replication related to concurrent BKV
  infection
• JCV viral capsid protein VP-1 found in 1/10
  biopsies
• confirming active viral transcription
• Exact role in pathogenesis of BKVN uncertain

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SV40 INFECTION IN RENAL ALLOGRAFTS

• SV40 accidentally infected 10-30 million humans
  beings who received vaccines produced in monkey
  kidney cells (1954-63)
• Recently SV40 sequences have been found by Dr
  Butel in allograft biopsies of 3 children born
  after 1963 (year in which monkey vaccines were
  discontinued)
• This raises a concern that continued transmission
  of this virus is occurring, it may be even be
  an occasional cause of allograft dysfunction