Impact of Tacrolimus Intra-Patient Variability on Toxicity Development Among Lung Transplant Recipients

Immunosuppressive treatment helps to reduce the risk of rejection after transplantation. However, it is important to be aware of the potential toxicities that can develop after this therapy initiation. Tacrolimus is currently the calcineurin inhibitor of choice in the post-transplantation immunosuppressive therapy, and its intra-patient variability (Tac-IPV) has been proposed in recent years as a useful biomarker in post-transplant outcomes. We performed an observational retrospective study in 195 lung transplant recipients to determine the potential impact of Tac-IPV as a biomarker in the development of cardiovascular toxicities and renal impairment in the post-transplantation evolution. Different Tac-IPV calculation measurements were shown to be statistically associated with the development of arterial hypertension de novo in the univariate analysis: the standard deviation (p = 0.016 for tacrolimus C_min values; p = 0.022 for tacrolimus dose-adjusted values); the coefficient of variation (p = 0.021 for C_min; p = 0.031 for dose-adjusted values); and the mean absolute deviation (MAD) (p = 0.043 for C_min; p = 0.033 for dose-adjusted values). Those patients with a MAD ≥ 16.47% had a higher risk of renal impairment (p = 0.045). In our study, different Tac-IPV measures were associated with arterial hypertension in lung transplantation follow-up. Patients with a high Tac-IPV, using the MAD as a measurement, showed a higher risk for renal impairment. No other statistically significant associations were found for the other studied events.