An observational retrospective study involving 195 lung transplant recipients suggests that tacrolimus intra-patient variability (Tac-IPV) may serve as a biomarker for post-transplantation complications, with several measures of Tac-IPV statistically associated with de novo arterial hypertension and high Tac-IPV as measured by MAD associated with higher risk for renal impairment.
Key Findings
Results
Standard deviation of tacrolimus Cmin values and dose-adjusted values were statistically associated with development of de novo arterial hypertension in univariate analysis.
Standard deviation of tacrolimus Cmin values was associated with de novo arterial hypertension (p = 0.016)
Standard deviation of tacrolimus dose-adjusted values was associated with de novo arterial hypertension (p = 0.022)
Study population comprised 195 lung transplant recipients in an observational retrospective design
Results
Coefficient of variation of tacrolimus Cmin and dose-adjusted values were statistically associated with development of de novo arterial hypertension.
Coefficient of variation for Cmin values was associated with de novo arterial hypertension (p = 0.021)
Coefficient of variation for dose-adjusted values was associated with de novo arterial hypertension (p = 0.031)
Associations were identified in univariate analysis
Results
Mean absolute deviation (MAD) of tacrolimus Cmin and dose-adjusted values were statistically associated with development of de novo arterial hypertension.
MAD for Cmin values was associated with de novo arterial hypertension (p = 0.043)
MAD for dose-adjusted values was associated with de novo arterial hypertension (p = 0.033)
MAD was one of three Tac-IPV calculation measurements found to be associated with this outcome
Results
Patients with a MAD of tacrolimus intra-patient variability ≥ 16.47% had a higher risk of renal impairment.
The threshold for elevated Tac-IPV associated with renal impairment was MAD ≥ 16.47%
Association between high Tac-IPV by MAD and renal impairment was statistically significant (p = 0.045)
This finding applied to dose-adjusted tacrolimus values
Results
No statistically significant associations were found between Tac-IPV and other studied toxicity events beyond arterial hypertension and renal impairment.
The study examined cardiovascular toxicities and renal impairment as post-transplantation outcomes
Only de novo arterial hypertension and renal impairment showed statistically significant associations with Tac-IPV measures
No other events reached statistical significance in the analyses performed
Methods
The study was designed as an observational retrospective study in lung transplant recipients to evaluate Tac-IPV as a biomarker for post-transplant toxicities.
Total sample size was 195 lung transplant recipients
Tac-IPV was calculated using multiple methods: standard deviation, coefficient of variation, and mean absolute deviation (MAD)
Both tacrolimus Cmin values and dose-adjusted values were used in IPV calculations
Outcomes assessed included cardiovascular toxicities and renal impairment
Nogueiras-Álvarez R, Mora-Cuesta V, Cifrián-Martínez J, García-Saiz M. (2026). Impact of Tacrolimus Intra-Patient Variability on Toxicity Development Among Lung Transplant Recipients.. Basic & clinical pharmacology & toxicology. https://doi.org/10.1111/bcpt.70229