title: Clearance of BK Virus Nephropathy by Combination Antiviral Therapy With Intravenous Immunoglobulin.
abstract: BACKGROUND
  Reactivation of BK polyoma virus causes a destructive virus allograft nephropathy (BKVAN) with graft loss in 46%. Treatment options are limited to reduced immunosuppression and largely ineffective antiviral agents. Some studies suggest benefit from intravenous immunoglobulin (IVIG).
  
  
  METHODS
  We evaluated effectiveness of adjuvant IVIG to eliminate virus from blood and tissue, in a retrospective, single-center cohort study, against standard-of-care controls. Both groups underwent reduced immunosuppression; conversion of tacrolimus to cyclosporine; and mycophenolate to leflunomide, oral ciprofloxacin, and intravenous cidofovir.
  
  
  RESULTS
  Biopsy-proven BKVAN occurred in 50 kidneys at 7 (median interquartile range, 3-12) months after transplantation, predominantly as histological stage B (92%), diagnosed following by dysfunction in 46%, screening viremia in 20%, and protocol biopsy in 34%. After treatment, mean viral loads fell from 1581 ± 4220 × 103copies at diagnosis to 1434 ± 70 639 midtreatment, and 0.138 ± 0.331 after 3 months (P< 0.001). IVIG at 1.01 ± 0.18 g/kg was given to 22 (44%) patients. The IVIG group more effectively cleared viremia (hazard ratio, 3.68; 95% confidence interval, 1.56-8.68;P= 0.003) and BK immunohistochemistry from repeated tissue sampling (hazard ratio, 2.24; 95% confidence interval, 1.09-4.58;P= 0.028), and resulted in faster (11.3 ± 10.4 months vs 29.1 ± 31.8 months,P= 0.015) and more complete resolution of viremia (33.3% vs 77.3%,P= 0.044). Numerically, fewer graft losses occurred with IVIG (27.3% vs 53.6% for control,P= 0.06), although graft and patient survivals were not statistically different. Acute renal dysfunction requiring pulse corticosteroid was common (59.1% vs 78.6%,P= 0.09), respectively, after immunosuppression reduction.
  
  
  CONCLUSIONS
  Combination treatment incorporating adjuvant IVIG was more effective eliminating virus from BKVAN, compared with conventional therapy. Validation by multicenter randomized trial is needed.
authors.affiliation: Renal Transplant Unit, Westmead Hospital, Sydney, Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Kable
authors.affiliation: Renal Transplant Unit, Westmead Hospital, Sydney, Australia.
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Davies
authors.affiliation: Renal Transplant Unit, Westmead Hospital, Sydney, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: O'connell
authors.affiliation: Renal Transplant Unit, Westmead Hospital, Sydney, Australia.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
authors.affiliation: Renal Transplant Unit, Westmead Hospital, Sydney, Australia.
authors.forename: Brian John
authors.initials: BJ
authors.lastname: Nankivell