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Towards personalization in kidney transplant

Tuesday September 13, 2022 - 11:35 to 13:05

Room: C2

311.6 The effect of tacrolimus and mycophenolic acid on TTV loads in kidney transplant recipients

Aline L van Rijn, Netherlands

PhD candidate
Medical Microbiology
Leiden University Medical Center


The effect of tacrolimus and mycophenolic acid on TTV loads in kidney transplant recipients

Aline van Rijn1, Soufian Meziyerh2, Danny van der Helm2, Teun van Gelder3, Aloysius CM Kroes1, Johan W de Fijter2, Dirk Jan AR Moes3, Joris I Rotmans2, Aiko PJ de Vries2, Mariet CW Feltkamp1.

1Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands; 2Internal Medicine, Leiden University Medical Center, Leiden, Netherlands; 3Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands

Background: 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 on 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 and mycophenolic acid levels and TTV levels was not found in the present study. The low R2 values and absence of an association in the adjusted analyses indicate that the high variation in TTV loads is not explained in a linear relationship with drug exposure levels, nor the known covariates. Future study will investigate different timeframes, non-linear relationships and drug exposure and TTV trajectories over time.

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