IVIG for Refractory BK Virus-Associated Nephropathy
IVIG can be considered as salvage therapy in this specific clinical scenario—biopsy-proven BKVN that continues to progress despite maximal tolerated immunosuppression reduction and when cidofovir or foscarnet are contraindicated or have failed—though the evidence base consists only of case series and reports, not randomized trials. 1
Guideline Framework
The American Society of Transplantation and KDIGO guidelines establish a clear hierarchy:
Immunosuppression reduction remains the only intervention with proven efficacy for preventing graft loss and should have been maximized first (which has been done in your patient). 1
IVIG is not recommended as first-line or standard therapy because no high-quality evidence demonstrates superiority over immunosuppression reduction alone. 1
IVIG should be reserved exclusively for biopsy-proven BKVN that progresses despite maximal, tolerated immunosuppression reduction—which describes your clinical scenario. 1
Low-dose cidofovir (1 mg/kg IV weekly without probenecid) and foscarnet are the guideline-endorsed adjunctive options before IVIG, but you've stated these are contraindicated or have failed. 1, 2
Evidence Supporting IVIG Use in Your Scenario
Since you've exhausted guideline-recommended options, the available evidence for IVIG includes:
A 2015 case series (n=30) showed 90% clearance of viremia with mean BK viral load dropping from 205,314 to 697 copies/mL after 1 year, with 96.7% graft survival at 12 months in patients who failed immunosuppression reduction and leflunomide. 3
A 2012 pediatric series reported successful BKV clearance in three patients and histological resolution in a fourth following IVIG at 2 g/kg after persistent viremia despite immunosuppression reduction. 4
A 2024 case report documented viremia declining from >2 million copies/mL to 5,500 copies/mL at 52 months after two doses of IVIG (2 g/kg) in a patient with class 2/B2 BKVN who failed tacrolimus discontinuation. 5
A 2006 case series (n=8) showed 88% graft survival at 15 months following IVIG therapy combined with immunosuppression reduction. 6
Critical Caveat: Contradictory Evidence
One 2014 case report documented exponential increase in BK viremia and progression to overt BKVN following high-dose IVIG administered for acute cellular rejection in a patient with pre-existing BK viremia. 7 This raises concern that IVIG may worsen BKV in some contexts, though this occurred when IVIG was given for rejection (increasing effective immunosuppression) rather than as targeted BKV therapy after maximal immunosuppression reduction.
Practical Implementation Algorithm
If you proceed with IVIG in this refractory case:
Administer 2 g/kg as a single dose, which is the regimen used in all positive case series. 5, 4, 3, 6
Monitor renal function before infusion due to high protein load that the allograft must tolerate. 1
Watch for infusion-related adverse events: volume overload, headache, chills, rigors, fever, and myalgia during administration. 1
Check quantitative plasma BK viral load weekly initially after IVIG to assess virologic response. 2
Monitor serum creatinine at least twice weekly during the first month to detect either improvement or deterioration. 2
Be prepared to repeat IVIG dosing: the 2024 case report used two doses (at 22 and 33 months post-transplant) before achieving sustained virologic response. 5
Continue close surveillance for acute rejection since you cannot further reduce immunosuppression and are not augmenting it. 1
Key Pitfalls in This Scenario
Do not use IVIG if you have not truly maximized immunosuppression reduction—antimetabolites should be discontinued (not just reduced) and calcineurin inhibitors minimized to the lowest level that prevents rejection. 1
Do not expect rapid virologic response—the 2024 case showed viremia initially increased to 2 million copies/mL three months after the first IVIG dose before eventually declining. 5
Do not abandon monitoring—even if IVIG appears ineffective initially, sustained benefit may take 6-12 months to manifest. 5, 3
Recognize this is off-guideline salvage therapy with only case series evidence; all authors acknowledge the need for randomized controlled trials to confirm efficacy. 5, 4, 3
Decision Point
Given that you have exhausted guideline-recommended therapies (maximal immunosuppression reduction, cidofovir/foscarnet contraindicated or failed) and face the alternative of progressive graft loss, IVIG represents a reasonable salvage option with 88-96.7% graft survival reported in case series, accepting that the evidence quality is low and one case report suggests potential harm. 3, 6, 7