Pediatric nephrology (Berlin, Germany) · 2025
Influence of intrapatient variability in tacrolimus trough levels on acute rejection in pediatric kidney transplant recipients.
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Fadel Fatina I, Makar Samuel H, Abbas Esraa Ehab, Mostafa Mahmoud Ibrahim, Mobarez Mohamed Ahmed, Othman Shorouk A
Аннотация
BACKGROUND: Tacrolimus is a cornerstone of lifelong immunosuppressive therapy to prevent acute rejection post-kidney transplantation. Tacrolimus intra-patient variability (IPV) is characterized by several pharmacokinetic metrics, including the standard deviation (SD) of tacrolimus troughs, coefficient of variation (CV%), dose-normalized concentration (DNC), and time in therapeutic range (TTR). This study aimed to investigate the influence of TTR, alongside other IPV metrics, on the incidence of acute rejection in the first year after kidney transplantation.
METHODS: This single-center retrospective study evaluated the relationship between IPV measures including coefficient of variation (CV%), standard deviation (SD), dose-normalized concentration (DNC), time in therapeutic range (TTR), and acute rejection during the first post-transplant year in 100 pediatric kidney recipients.
RESULTS: Patients were stratified by TTR into two subgroups: TTR < 78% (n = 80) and TTR ≥ 78% (n = 20). The mean CV% of tacrolimus concentration was 37.1 ± 16.6%, with significantly higher variability observed in those with rejection (p = 0.031). Longitudinal analysis showed that differences in trough levels between TTR groups became evident after 3 months (p < 0.001). Multivariable modeling demonstrated that rejection risk was independently associated with higher age (p = 0.002) and post-transplant period beyond 3 months (p = 0.004), rather than TTR itself.
CONCLUSIONS: In pediatric kidney transplant patients, the rejection risk was significantly associated with the magnitude of CV% rather than TTR. Special attention is warranted for therapeutic drug monitoring, especially beyond 3 months post-transplant, due to the increased risk of rejection compared to earlier stages post-transplantation.
METHODS: This single-center retrospective study evaluated the relationship between IPV measures including coefficient of variation (CV%), standard deviation (SD), dose-normalized concentration (DNC), time in therapeutic range (TTR), and acute rejection during the first post-transplant year in 100 pediatric kidney recipients.
RESULTS: Patients were stratified by TTR into two subgroups: TTR < 78% (n = 80) and TTR ≥ 78% (n = 20). The mean CV% of tacrolimus concentration was 37.1 ± 16.6%, with significantly higher variability observed in those with rejection (p = 0.031). Longitudinal analysis showed that differences in trough levels between TTR groups became evident after 3 months (p < 0.001). Multivariable modeling demonstrated that rejection risk was independently associated with higher age (p = 0.002) and post-transplant period beyond 3 months (p = 0.004), rather than TTR itself.
CONCLUSIONS: In pediatric kidney transplant patients, the rejection risk was significantly associated with the magnitude of CV% rather than TTR. Special attention is warranted for therapeutic drug monitoring, especially beyond 3 months post-transplant, due to the increased risk of rejection compared to earlier stages post-transplantation.