*Purpose: Measuring immune function in kidney transplant recipients (KTRs) remains challenging given the precarious balance between over- and underimmunosuppression. This is primarily due to high inter- and intrapatient variability in pharmacokinetics and -dynamics of both tacrolimus (tac) and mycophenolic acid (mpa) and their narrow therapeutic window. Torque teno virus (TTV), a non-pathogenic commensal virus, has been proposed as marker of immune function: high loads may correspond to over-immunosuppression, and low loads to under-immunosuppression. An inverse relation between TTV load and acute rejection has already been shown. This study aimed to investigate the effect of tac and mpa exposure on TTV loads in KTRs.

*Methods: A cross-sectional cohort study was designed using a unique database of drug exposure data. KTRs transplanted between 2005-2012 and started with tac/mpa/prednisolone were included. Patients without exposure data, without available samples for TTV load measurement or switches in therapy were excluded, leaving 170 KTR for analysis on month 3 and 159 on month 6. Linear regression was used to study the association between TTV loads and tac through (C₀) levels, and tac and mpa area-under-the-curve (AUC) data, measured on the day of, and 2 weeks before TTV load measurement. Analyses were adjusted for donor and recipient age and gender, number of human leukocyte antigen (HLA) mismatch, days on dialysis, and induction therapy.

*Results: Linear regression showed an increase in predicted TTV load at month 3 with tac C₀ and AUC increase in the univariate analysis (C₀: β=0.20 per 1 μg/L, p=0.01, R2=0.04); AUC: β=0.18 per 20 mg*h/L, p=0.05, R2=0.04), but not in the analysis adjusted for confounders (C₀: β=0.16 per 1 μg/L, p=0.15, R2=0.08); AUC: β=0.01 per 20 mg*h/L, p=0.17, R2=0.08) for exposure samples taken on the same day as the TTV sample. Similar results were found when using samples taken 2 weeks before. For MPA no association was found. Analyses on month 6 showed similar results.

*Conclusions: An association between tacrolimus exposure and TTV levels seems present, but subtle. The low R² values and absence of an association in the adjusted analyses indicate that most variation in TTV loads is not explained by drug exposure at the same day or 2 weeks before. The presence of an association with Tac exposure and absence of effect of MPA exposure provides insight into the immune response that controls TTV replication. Future study will examine different timeframes after transplantation and other covariates that might explain the high variation in TTV loads.

« Back to 2022 American Transplant Congress