In an adult kidney‑transplant recipient with confirmed BK‑virus replication, how should intravenous immunoglobulin (IVIG) be administered (dose and schedule) and monitored as adjunctive therapy?

IVIG Therapy in BK Virus Post Renal Transplant

IVIG is not recommended as first-line therapy for BK virus nephropathy; reduction of immunosuppression is the only intervention with established efficacy and should be implemented immediately when plasma BK viral load persistently exceeds 10,000 copies/ml. 1, 2

Primary Management Algorithm

Step 1: Immediate immunosuppression reduction when BKV plasma NAT persistently exceeds 10,000 copies/ml (10^7 copies/L) 1, 2

• Reduce or temporarily discontinue antimetabolites (mycophenolate mofetil or azathioprine) first 2
• This is the only intervention with proven efficacy for preventing graft loss 2
• Do not delay reduction while awaiting biopsy confirmation—early intervention prevents progression 2

Step 2: Monitor response with serial plasma BK viral loads 1

• Continue monthly screening for the first 3-6 months post-transplant 1, 2
• Screen every 3 months until the end of the first post-transplant year 1, 2
• Perform additional testing whenever unexplained serum creatinine elevation occurs 1, 2
• Screen after treatment for acute rejection 1, 2

IVIG as Adjunctive Therapy: When and How

IVIG should only be considered for biopsy-proven BKVN that progresses despite maximal immunosuppression reduction and failure of first-line therapy after 8 weeks. 2, 3

Dosing Protocol When IVIG Is Used

• Dose: 2 g/kg intravenously 3, 4, 5
• Schedule: Single dose initially, with repeat dosing at 11 months if viremia persists or increases 4
• Alternative dosing: 1 g/kg has been used in some protocols 6

Evidence Supporting IVIG Use

The evidence for IVIG is limited to case series and retrospective studies, not randomized controlled trials:

• A 2015 case series of 30 patients showed 90% clearance of viremia with IVIG after failure of immunosuppression reduction and leflunomide, with 96.7% graft survival at 12 months 3
• A 2017 retrospective cohort study demonstrated faster viremia clearance (hazard ratio 3.68) and more complete resolution (77.3% vs 33.3%) with IVIG compared to standard therapy alone 6
• A 2012 pediatric series showed successful clearance in 3 of 4 patients with persistent BKV after immunosuppression reduction 5
• However, a 2014 study found no significant difference in 1-year graft outcomes between active management with IVIG and immunosuppression reduction alone 7

Monitoring During IVIG Therapy

• Measure plasma BK viral load every 2-4 weeks during treatment 3, 4
• Monitor serum creatinine at least twice weekly initially 8
• Repeat kidney biopsy if creatinine continues rising or proteinuria worsens despite therapy over 7-10 days 8
• Watch for acute rejection episodes, which occurred in 59-79% of patients after immunosuppression reduction in one series 6

Critical Pitfalls to Avoid

• Do not use IVIG as first-line therapy—immunosuppression reduction is the only proven intervention 2
• Do not delay immunosuppression reduction while awaiting biopsy or considering IVIG—early intervention is critical 2
• Avoid precipitous over-reduction of immunosuppression that triggers acute rejection—gradual reduction with close monitoring is essential 2
• Do not rely solely on urine BK testing—plasma viral load is more specific for nephropathy risk 2
• Avoid using decoy cells alone for diagnosis—they lack sensitivity and require PCR confirmation 2

Alternative Adjunctive Therapies

If IVIG fails or is unavailable:

• Low-dose cidofovir (1 mg/kg IV weekly without probenecid) can be considered only for biopsy-proven, progressive BKVN despite maximal immunosuppression reduction 2
• Foscarnet represents an alternative if cidofovir is contraindicated, but requires close monitoring for electrolyte abnormalities (hypocalcemia, hypophosphatemia, hypomagnesemia) 2
• Leflunomide has been used in combination protocols, though evidence is limited 3, 7

Realistic Clinical Approach

Given the lack of high-quality evidence for IVIG and the strong guideline recommendation for immunosuppression reduction as the only proven therapy, IVIG should be reserved for salvage therapy in patients with biopsy-proven BKVN who have failed 8 weeks of maximal immunosuppression reduction. 2, 3 The dose of 2 g/kg appears most commonly used, with repeat dosing guided by viral load response. 3, 4, 5 Close monitoring for rejection and graft function is mandatory, as the risk of acute rejection increases substantially when immunosuppression is reduced. 6