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

Area of Science:

• Transplantation immunology
• Pharmacogenomics
• Nephrology

Background:

• Immunosuppressive therapy is crucial post-transplantation to prevent organ rejection.
• Tacrolimus (Tac) is a primary calcineurin inhibitor used in immunosuppression.
• Tacrolimus intra-patient variability (Tac-IPV) is emerging as a potential biomarker for transplant outcomes.

Purpose of the Study:

• To investigate the association between Tac-IPV and cardiovascular toxicities, specifically de novo arterial hypertension.
• To assess the impact of Tac-IPV on renal impairment following lung transplantation.
• To evaluate different Tac-IPV calculation methods as predictive biomarkers.

Main Methods:

• Observational retrospective study involving 195 lung transplant recipients.
• Analysis of tacrolimus trough concentrations (Cmin) and dose-adjusted values.
• Calculation and statistical analysis of various Tac-IPV metrics: standard deviation, coefficient of variation, and mean absolute deviation (MAD).

Main Results:

• Several Tac-IPV measures (standard deviation, coefficient of variation, MAD) were significantly associated with de novo arterial hypertension in univariate analysis.
• Patients with a MAD ≥ 16.47% demonstrated a higher risk of developing renal impairment (p=0.045).
• No significant associations were found for other cardiovascular events or outcomes.

Conclusions:

• Different Tac-IPV measurements are linked to arterial hypertension in lung transplant recipients.
• High Tac-IPV, measured by MAD, is a predictor of increased renal impairment risk.
• Tac-IPV serves as a valuable biomarker for monitoring post-lung transplant complications.