Intravenous immunoglobulin and mammalian target of rapamycin inhibitors for treatment of BK virus infections in kidney transplantation: a systematic review

BACKGROUND: Reduction of immunosuppression (ROI) remains the mainstay of treatment for BK virus infection (BKVI) in kidney transplantation (KT). This review explored the role of intravenous immunoglobulin (IVIG) and mammalian target of rapamycin inhibitor (mTORi) regimens as alternative therapies for KT recipients with BKVI, focusing on viral clearance and graft-related outcomes. METHODS: An electronic search was conducted for articles examining IVIG or mTORi use in treating BKVI among adult and/or pediatric KT recipients. Meta-analyses of proportions were performed for relevant outcomes. RESULTS: Twenty-seven studies (13 evaluating IVIG and 14 evaluating mTORi) were included; all but three enrolled only adult participants. In IVIG studies, the pooled viral clearance rate was 76.4% (95% confidence interval [CI], 64.2%-85.5%), with numerically higher clearance for IVIG after ROI compared to IVIG with ROI (87.0% vs. 66.1%). Overall graft survival was 84.7% (95% CI, 70.7%-92.7%), with numerically higher survival in IVIG after ROI than in IVIG with ROI (93.6% vs. 78.4%). Pooled histological clearance and graft rejection rates were 82.8% and 14.5%, respectively. In mTORi studies, the pooled viral clearance rate was 68.0% (95% CI, 58.0%-76.7%) and overall graft survival was 89.1% (95% CI, 82.7%-93.4%), with no significant difference between patients with and without prior ROI. Histological clearance and graft rejection rates were 59.8% and 8.6%, respectively. CONCLUSIONS: IVIG and mTORi regimens appear to be feasible alternatives to ROI in KT recipients with BKVI, achieving viral clearance while maintaining graft survival. Future randomized controlled trials are needed to further define their role and strengthen current evidence with higher-quality data.