Pediatric nephrology (Berlin, Germany) · 2025
Association of intrapatient tacrolimus variability and concentration-to-dose ratio with outcomes in pediatric kidney transplantation.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Baghai Arassi Maral, Fisch Nora, Feißt Manuel, Krupka Kai, Höcker Britta, Fichtner Alexander, Kanzelmeyer Nele, König Jens, Melk Anette, Oh Jun, Pape Lars, Weber Lutz T, Weitz Marcus, Tönshoff Burkhard, CERTAIN Research Network, the ESPN working group on transplantation
Аннотация
BACKGROUND: Data on the relevance of tacrolimus intrapatient variability (TacIPV) and concentration-to-dose ratio (C/D ratio) as an approximation of tacrolimus metabolism for predicting outcomes in pediatric kidney transplant (pKTx) recipients are scarce.
METHODS: We conducted a multicenter retrospective study of 255 pKTx recipients from the CERTAIN registry. TacIPV was quantified as the coefficient of variation (CV%) during months 6-12 post-transplant. In addition, the C/D ratio, corrected for body surface area, was calculated for the first 6 months post-transplant. Cutoffs were determined by minimization of log-rank P values: 23% for TacIPV and 1.0 for C/D ratio. Rejection episodes were classified according to the Banff criteria in the period following marker quantification.
RESULTS: A total of 13,159 tacrolimus trough blood levels were analyzed, with a median of 52 (IQR, 41-63) measurements per patient. High TacIPV (> 23%) during months 6-12 post-transplant was associated with an increased risk of rejection beyond 12 months post-transplant (hazard ratio (HR) 1.04, 95% CI 1.01-1.06, P = 0.002; Kaplan-Meier analysis P = 0.002). Similarly, a low C/D ratio (< 1.0), i.e., rapid tacrolimus metabolism, during the first 6 months was associated with a higher risk of rejection between months 6 and 12 (inverse HR 3.13, 95% CI 1.01-9.09, P = 0.04; Kaplan-Meier analysis P = 0.011).
CONCLUSIONS: This largest to date multicenter study determines pediatric-specific cutoff values for TacIPV and tacrolimus C/D ratio as a predictive marker for graft rejection. Patients with these risk factors should be closely monitored and their immunosuppressive therapy adjusted accordingly.
METHODS: We conducted a multicenter retrospective study of 255 pKTx recipients from the CERTAIN registry. TacIPV was quantified as the coefficient of variation (CV%) during months 6-12 post-transplant. In addition, the C/D ratio, corrected for body surface area, was calculated for the first 6 months post-transplant. Cutoffs were determined by minimization of log-rank P values: 23% for TacIPV and 1.0 for C/D ratio. Rejection episodes were classified according to the Banff criteria in the period following marker quantification.
RESULTS: A total of 13,159 tacrolimus trough blood levels were analyzed, with a median of 52 (IQR, 41-63) measurements per patient. High TacIPV (> 23%) during months 6-12 post-transplant was associated with an increased risk of rejection beyond 12 months post-transplant (hazard ratio (HR) 1.04, 95% CI 1.01-1.06, P = 0.002; Kaplan-Meier analysis P = 0.002). Similarly, a low C/D ratio (< 1.0), i.e., rapid tacrolimus metabolism, during the first 6 months was associated with a higher risk of rejection between months 6 and 12 (inverse HR 3.13, 95% CI 1.01-9.09, P = 0.04; Kaplan-Meier analysis P = 0.011).
CONCLUSIONS: This largest to date multicenter study determines pediatric-specific cutoff values for TacIPV and tacrolimus C/D ratio as a predictive marker for graft rejection. Patients with these risk factors should be closely monitored and their immunosuppressive therapy adjusted accordingly.