In a kidney‑transplant recipient with BK virus nephropathy, should intravenous immunoglobulin (IVIG) be used as first‑line therapy, and what dosing regimen is recommended?

IVIG in BK Nephropathy

IVIG should NOT be used as first-line therapy for BK virus nephropathy in kidney transplant recipients; reduction of immunosuppressive medications is the only intervention with established efficacy and represents the standard of care. 1, 2

First-Line Management: Immunosuppression Reduction

The cornerstone of BK nephropathy treatment is immediate reduction of immunosuppressive therapy when plasma BK viral load persistently exceeds 10,000 copies/mL (10^7 copies/L). 1, 2 This is the only strategy supported by KDIGO guidelines with proven efficacy for preventing graft loss. 2

Immunosuppression Reduction Protocol

• Reduce or temporarily discontinue antimetabolites (mycophenolate mofetil or azathioprine) first. 2
• Continue tapering immunosuppression gradually until BK viral load declines, while monitoring closely for acute rejection. 2
• Do NOT delay immunosuppression reduction while awaiting kidney biopsy confirmation when plasma viral load exceeds 10,000 copies/mL—early intervention prevents progression to nephropathy. 2

Critical Monitoring Requirements

• Screen all kidney transplant recipients monthly for the first 3-6 months post-transplant using quantitative plasma nucleic acid testing (NAT). 1, 2
• Continue screening every 3 months through the end of the first post-transplant year. 1, 2
• Perform additional screening whenever unexplained serum creatinine elevation occurs or after treatment for acute rejection. 1, 2

IVIG as Second-Line Therapy Only

IVIG should be considered ONLY for biopsy-proven BK nephropathy that progresses despite maximal immunosuppression reduction. 2 This represents salvage therapy, not first-line treatment.

When to Consider IVIG

• Patient has persistent BK viremia (>10,000 copies/mL) after 8 weeks of adequate immunosuppression reduction. 3
• Biopsy-proven BK nephropathy continues to progress despite maximal tolerable immunosuppression reduction. 2, 3
• Rising creatinine or worsening graft function despite appropriate first-line management. 3, 4

IVIG Dosing Regimen

Administer IVIG at 2 g/kg as a single dose when indicated as second-line therapy. 3, 5, 6 This dosing has been consistently used across multiple case series showing viral clearance.

• Repeat dosing may be necessary if viremia persists or rebounds; one case report documented repeat dosing at 11 months after initial treatment. 4
• Monitor for infusion-related adverse events including volume overload, headache, chills, rigors, fever, and myalgia during administration. 2
• Assess renal function before administering IVIG due to the high protein load on the allograft. 2

Evidence Quality and Limitations

The evidence supporting IVIG use consists entirely of case reports and small case series, not randomized controlled trials. 3, 5, 4, 6 The largest series reported 90% viral clearance in 30 patients who failed immunosuppression reduction and leflunomide, with 96.7% graft survival at 12 months. 3 However, these patients received IVIG as adjunctive therapy after immunosuppression reduction, not as monotherapy.

The KDIGO guidelines do not recommend IVIG as standard therapy because no high-quality evidence demonstrates superiority over immunosuppression reduction alone. 1, 2

Alternative Second-Line Agents

If IVIG is unavailable or contraindicated:

• Low-dose cidofovir (1 mg/kg IV weekly without probenecid) can be considered for biopsy-proven, progressive BK nephropathy 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 with immunosuppression reduction, though evidence remains limited. 3, 7

Critical Pitfalls to Avoid

• Never use IVIG as first-line therapy before attempting immunosuppression reduction—this contradicts established guidelines and delays proven effective treatment. 1, 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 or decoy cells—plasma viral load >10,000 copies/mL is the threshold for intervention. 2
• Never delay treatment while awaiting biopsy if plasma viral load is persistently elevated—biopsy confirms diagnosis but should not delay immunosuppression reduction. 2