Management of Polyomavirus (BK Virus)  Infection in Kidney Transplant Patients GDCN Meeting March 10, 2013

5/30/2013
Management of Polyomavirus (BK Virus) Infection in Kidney Transplant Patients
GDCN Meeting
March 10, 2013
• Using modern surveillance protocols most diagnoses in first year
• Diagnoses after 2 years uncommon
• Rates of graft loss have improved considerably
Diagnosis of BKVAN (Single Center Studies)
< 1 year
1‐2 years
> 2 years
Hirsch. Transplantation 79:1277,2005
Pang. J. Clin Microbiol 45: 3568, 2007
Viscout. Transplantation 84:340, 2007
Babel. Transplantation 88:89, 2009
Singh. H. J Am Soc Neph 20:210, 2009
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PVN absent:
Reduce IS
Kidney Biopsy and EM Urinary Screen for Haufen
Early Biopsy Directed Approach
Viremia Detected
Any Level
Viremia
Negative Biopsy
Transplant Biopsy
Urine EM for Haufen
Viremia
Viremia
Viremia
BKVAN
Haufen
BK Nephropathy
No Rejection
No Biopsy (Technical)
Rejection
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Immunosuppression Reduction:
The Cornerstone of Therapy
Antimetablolites
Calcineurin Inhibitors
Corticosteroids
• Reduce dose
• Discontinuation
• Replace with leflunomide
• Reduce dose (Tacrolimus level 4‐6 ng/ml)
• Discontinuation • Initiate in steroid free patients • Taper in steroid treated patients
Antiviral Options
Treatment of BK Virus Infection
Leflunomide
Cidofovir
IVIG
Fluoroquinolones
• Anti‐inflammatory properties, inhibits BKV replication
• Drug level dependent
• Hepatotoxicity
• Thrombocytopenia, hemolytic anemia (TMA), leukopenia
• In vitro activity against BKV
• Nephrotoxic
• Anti‐BKV neutralizing antibodies
• Immunomodulatory effect may be advantageous
• Serum sickness, fluid overload, expensive
• In vitro activity
• Prophylaxis studies only
• Long term therapy = tendon rupture, AIN risk
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Johnston et al, Transplantation 89:1057‐1070, 2010
Johnston et al, Transplantation 89:1057‐1070, 2010
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Cumulative Results for Treatment of BK Virus Infection (State of the Literature) • Graft survival – highly variable
• Rejection – highly variable, rates up to 30%
• Clearance of Viremia – 90% of cases, median 8 months
• Ureteric involvement, obstruction rare
• Hemorrhagic cystitis, uncommon except in stem cell transplants
• Drug toxicities ‐ variable
Johnston et al, Transplantation 89:1057‐1070, 2010
Biopsy Directed Therapy (UNC Approach)
Viremia Only
No BKVAN
No Rejection
Viremia
Viremia BKVAN
Haufen (no Biopsy)
Viremia
Rejection
BKVAN
Pulse Solumedrol
Reduce MMF/MPS 50%
Stop MMF/MPS
Tacrolimus Level Target 4‐6 ng/ml
Tacrolimus Target 4‐6 ng/ml
Stop MMF/MPS
Consider Starting Prednisone
Consider Starting Leflunomide and/or Prednisone
Add Leflunomide and Prednisone
Same as BKVAN
Rarely Thymoglobulin
Refractory or advanced cases consider IVIG, fluoroquinolones
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Prevention Strategies
Surveillance Screening
• Monthly for 3 to 6 months then q 2 to 3 months until 2 years
• Recommend urinary screening or plasma PCR
• Beyond 2 years screen yearly or for allograft dysfunction
Tailored Immunosuppression
• Viruria, viremia induced treatment strategy
• Risk assessment analysis – rejection vs. infection
• Measures of immunocompetence
Antiviral Prophylaxis
• Fluoroquinoles
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Preemptive Immunosuppression Reduction
• Discontinuation of antimetabolite upon detection of viremia resulted in clearance of BK viremia 95%, no graft losses to BKVAN
• BK viral clearance accomplished in 90% in other studies
• 8.6‐36.3% rejection rates following BKVAN, no apparent effect on graft outcome Brennan, D. Am J Transpl 5: 582‐594, 2005
Hardinger, K. Am J Transpl 10:407‐415, 2010
Bennett, W. Am J Nephrol 32:10‐12, 2010
Almeras, C. Transpl 85:1099‐1104, 2008
Schaub, S. Am J Transpl 10:2615‐2623, 2010
BK Virus Nephropathy
Risk Factors
Age >65 years
Male recipient
Deceased donor
Higher HLA mismatch
Recipient BK antibody seronegative
• Reduced dendritic cell numbers
• Urinary Stents •
•
•
•
•
• Early Rejection
• Cumulative prednisone dose • Rabbit Anti‐thymocyte globulin induction
• Tacrolimus/MMF maintenance regimen
• Viral co‐infection
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Fluoroquinolone Effect
Gyrase
Ciprofloxacin Prophylaxis
Group 1: no Cipro (n = 106)
Group 2: 30 days Cipro prophylaxis (n=130)
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Thank You
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