Association of Torque Teno Virus DNA Load and Tacrolimus in Peripheral Blood Mononuclear Cells of Adult Kidney Transplant Patients.

BACKGROUND

Emerging strategies for tacrolimus dose optimization in kidney transplant recipients include measuring drug concentrations in peripheral blood mononuclear cells (PBMCs) and biomarkers of immunosuppression, such as torque teno virus (TTV), which reflects the relative immunosuppression of the host. This study examined the association between tacrolimus in whole blood/PBMCs and serum TTV DNA load.

METHODS

Dense (n = 18) or sparse (n = 45) blood sampling was performed on 63 stable kidney transplant recipients. PBMCs were isolated using Ficoll density gradient centrifugation, and tacrolimus concentrations were quantified in whole blood and PBMCs using liquid chromatography and triple quadrupole mass spectrometry. TTV load was assessed using qPCR. Tacrolimus exposure in whole blood and PBMCs was predicted as empirical Bayes estimates using a population pharmacokinetic model. The correlation between tacrolimus exposure and TTV load was assessed using Spearman correlations and t-tests.

RESULTS

The median time since transplantation was 38 months (interquartile range: 15-79). Around 60% of patients had detectable TTV DNA in serum (median: 4.2 log10 copies/mL, interquartile range: 3.6-4.9). There was no significant difference in average steady-state tacrolimus concentration (Css,av) in whole blood (P = 0.45) or in PBMCs (P = 0.57) between patients with or without detectable TTV. Greater TTV load was not associated with greater tacrolimus Css,av in whole blood (P = 0.15) or in PBMCs (P = 0.73). TTV load was generally lower in patients with longer time since transplantation (P = 0.05).

CONCLUSIONS

Tacrolimus exposure in whole blood or PBMCs is not associated with TTV DNA load in kidney transplant patients.