IVIG in BK Virus Associated Nephropathy
IVIG should be considered as second-line therapy for BK virus associated nephropathy (BKVAN) when immunosuppression reduction and leflunomide fail to clear viremia after 8 weeks, with dosing at 2 g/kg or 100 mg/kg/day for 5 days showing efficacy in clearing viremia and preventing graft loss. 1, 2
Primary Treatment Approach
The established first-line management for BKVAN remains reduction of immunosuppression, as this is the only proven therapy according to current guidelines 3, 4. However, this approach alone frequently fails to control viral replication and prevent graft dysfunction.
When to Consider IVIG
IVIG should be initiated when patients demonstrate:
- Persistent BK viremia (>15,000-100,000 copies/mL) despite 8 weeks of immunosuppression reduction 1
- Progressive increase in viral load despite standard interventions 4, 5
- Biopsy-proven BKVAN with ongoing viral replication 5, 2
- Failure to clear decoy cells from urine after discontinuing mycophenolate 2
Evidence Supporting IVIG Efficacy
The strongest recent evidence comes from multiple studies demonstrating substantial benefit:
A 2017 retrospective cohort study showed IVIG significantly improved viremia clearance (hazard ratio 3.68, p=0.003) and cleared BK immunohistochemistry from tissue faster (11.3 vs 29.1 months, p=0.015) compared to standard therapy alone 5
A 2015 study of 30 patients with persistent BKVN showed 90% positive response in clearing viremia after IVIG, with 12-month graft survival of 96.7% 1
A 2020 Japanese study demonstrated that all five BKVAN cases showed diminished SV40 large T antigens after IVIG, with improved polyomavirus nephropathy classification 2
Dosing Protocols
Two effective dosing regimens have been reported:
- 2 g/kg as a single dose (can be repeated if needed at intervals of weeks to months) 4, 6
- 100 mg/kg/day for 5 consecutive days 2
Both protocols appear effective, though the 2 g/kg single-dose regimen is more commonly reported in the literature 4, 1, 6.
Combination Treatment Strategy
The optimal approach combines:
- Reduction of immunosuppression (decrease tacrolimus, discontinue or reduce mycophenolate) 1, 5, 2
- Conversion from tacrolimus to cyclosporine when appropriate 5
- Addition of leflunomide 1, 5
- Oral ciprofloxacin 5
- Intravenous cidofovir (though evidence is limited) 5
- IVIG as adjuvant therapy when the above measures fail 1, 5
Monitoring Response
After IVIG administration, monitor:
- BK viral load in plasma every 2-4 weeks initially - expect decline within 3 months 4, 5
- Urine decoy cells - should decrease or clear 2, 6
- Serum creatinine and renal function 3, 7
- Consider repeat biopsy if renal function deteriorates despite viral load reduction 7
Important Caveats
Acute rejection risk increases substantially after immunosuppression reduction - occurring in 59-79% of patients 5. This may require pulse corticosteroids and careful differentiation from BKVAN progression, as both can present with rising creatinine 3, 7.
The evidence base consists primarily of case reports and small retrospective series 4, 1, 5, 2, 6. No randomized controlled trials have been conducted, though the consistency of positive results across multiple studies is encouraging 5.
IVIG appears safe with no significant adverse effects reported in the available studies 1, 6.
Practical Algorithm
- Diagnose BKVAN via biopsy with confirmatory immunohistochemistry or in-situ hybridization 3, 7
- Reduce immunosuppression and add leflunomide 1, 5
- Monitor viral load every 2-4 weeks 7
- If viremia persists or increases after 8 weeks, administer IVIG 2 g/kg 1
- Continue monitoring; repeat IVIG if viremia rebounds 4
- Maintain vigilance for acute rejection with concurrent monitoring 7, 5