Apparent Elevation of Whole-Blood Tacrolimus Concentrations Following High-Dose Intravenous Immunoglobulin Therapy in...

The effect of massive immunoglobulin G (IgG) elevation on highly protein-bound tacrolimus (TAC) after high-dose intravenous immunoglobulin (IVIG) therapy remains uncharacterized. Misinterpreting IVIG-induced whole-blood TAC elevation as increased unbound fraction risks underdosing and rejection in donor-specific antibody-positive kidney transplant recipients. The aim of this study was to investigate the interaction between IVIG-induced IgG elevation and TAC during preoperative desensitization.

This retrospective study compared TAC trough levels (C0), area under the concentration-time curve from 0 to 24 hours (AUC0-24), TAC C0/dose (C0/D), TAC AUC0-24/dose (AUC0-24/D), and serum IgG levels predesensitization and postdesensitization among 3 groups: IVIG [high-dose IVIG plus plasmapheresis (PP), n = 12], PP only (n = 7), and control (n = 68).

Following IVIG, median whole blood TAC C0 rose from 6.5 to 9.3 ng/mL and AUC0-24 from 238.2 to 325.8 ng·hours/mL. Accordingly, serum IgG levels increased from 968 (898-1396) to 2647 (2349-2927) mg/dL. A linear mixed model confirmed that an increase in serum IgG levels was independently associated with an elevated TAC AUC0-24/D. This apparent TAC AUC0-24/D increase peaked at 1.3-fold and persisted for 2 weeks; however, no clinical evidence of TAC toxicity (eg, hyperkalemia) was observed, suggesting an unlikely rise in the unbound concentration.

IVIG induced an apparent elevation in whole-blood TAC concentrations, mediated by elevated serum IgG levels. Because this elevation theoretically may not reflect an increase in the unbound fraction, empirical dose reductions based solely on whole-blood levels risk compromising immunosuppression. A vigilant therapeutic drug monitoring strategy is essential to account for the protein-binding interaction and potentially optimize immunosuppression in high-risk patients.