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POLYOMAVIRUS INFECTION IN RENAL ALLOGRAFTS: PROGRESS SINCE BANFF 1999

POLYOMAVIRUS INFECTION IN RENAL ALLOGRAFTS: PROGRESS SINCE BANFF 1999. Parmjeet Randhawa Associate Professor Division of Transplantation Pathology Department of Pathology University of Pittsburgh. SCOPE OF PROGRESS. BKV infection JCV infection SV40 infection.

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POLYOMAVIRUS INFECTION IN RENAL ALLOGRAFTS: PROGRESS SINCE BANFF 1999

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  1. POLYOMAVIRUS INFECTION IN RENAL ALLOGRAFTS: PROGRESS SINCE BANFF 1999 Parmjeet Randhawa Associate Professor Division of Transplantation Pathology Department of Pathology University of Pittsburgh

  2. SCOPE OF PROGRESS • BKV infection • JCV infection • SV40 infection

  3. MORPHOLOGIC SPECTRUM OF BKVN • Silent viral inclusions • Acute tubular necrosis • Viral interstitial nephritis • Basel group believes in concurrent rejection

  4. 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

  5. THERAPEUTIC CONSIDERATIONS IN BKVAN • Most centers reduce immunosuppression • Basel group feels steroids indicated in cases with concurrent rejection but they also reduce immsup later (n=5) • Pittsburgh finds worse prognosis if steroids given: 58% graft loss (n=12) vs 10% (n=18) • Anti-viral drugs are being tried empirically

  6. 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 MONITORING BKV LOAD IN CLINICAL SPECIMENS • Urine cytology • Urinary PCR • Blood PCR

  7. 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 >5 decoy cells/10hpf trigger plasma PCR; positive PCR triggers biopsy

  8. 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 withdecoy cells in urine

  9. 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

  10. 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

  11. 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

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