The predictive value of tacrolimus intrapatient variability and time in therapeutic range for renal transplant outcomes.

Background: Tacrolimus is key in renal transplantation. This study evaluated optimal intrapatient variability (IPV) and time in therapeutic range (TTR) thresholds and association with renal outcomes.

Methods: This single-center study (1999-2018) had a mean follow-up of 3 years. All patients received tacrolimus-based immunosuppression, and excluded those switching from cyclosporin. Receiver operating characteristic curves evaluated IPV and TTR cutoff values for biopsy-proved acute rejection (BPAR). Cox regression, -square, Mann-Whitney U, Kaplan-Meier, and log-rank tests were used for outcome analysis.

Results: The cohort included 463 patients (mean age 47.3 years; 44.1% female). Most received cadaveric grafts (66.4%) and ABO-compatible transplants (97.4%). Preexisting diabetes and hypertension were present in 14.7% and 63.7%, respectively. Mean tacrolimus trough level was 7.28 ± 1.92 ng/mL. Patients with IPV ≥25.6% had increased doubling of serum creatinine (DSCr) at 6-12 months ( = 0.007) and within 5 years ( < 0.001), and higher BPAR within 1 year ( = 0.025). Similarly, TTR <81.1% was associated with increased DSCr at 6-12 months ( = 0.015) and within 5 years ( = 0.009), and higher graft failure rates ( = 0.001). An IPV <25.6% was also associated with a lower risk of DSCr within 5 years (HR 0.11; 95% CI, 0.03-0.50) and BPAR within one year (HR 0.59; 95% CI, 0.35-0.98), as shown in the Cox proportional hazards analysis. Kaplan-Meier analysis demonstrated significantly lower survival in patients with IPV ≥25.6% compared to IPV <25.6% ( = 0.028), but no significant survival difference between TTR groups ( = 0.337).

Conclusion: IPV and TTR are valuable for predicting renal transplant outcomes, with IPV demonstrating stronger predictive ability. Minimizing IPV through frequent monitoring and adherence support could enhance graft survival.