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Background <p>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.</p> Methods <p>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&#xa0;months post-transplant. Cutoffs were determined by minimization of log-rank <i>P</i> 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.</p> Results <p>A total of 13,159 tacrolimus trough blood levels were analyzed, with a median of 52 (IQR, 41–63) measurements per patient. High TacIPV (&gt; 23%) during months 6–12 post-transplant was associated with an increased risk of rejection beyond 12&#xa0;months post-transplant (hazard ratio (HR) 1.04, 95% CI 1.01–1.06, <i>P</i> = 0.002; Kaplan–Meier analysis <i>P</i> = 0.002). Similarly, a low C/D ratio (&lt; 1.0), i.e., rapid tacrolimus metabolism, during the first 6&#xa0;months was associated with a higher risk of rejection between months 6 and 12 (inverse HR 3.13, 95% CI 1.01–9.09, <i>P</i> = 0.04; Kaplan–Meier analysis <i>P</i> = 0.011).</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

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Association of intrapatient tacrolimus variability and concentration-to-dose ratio with outcomes in pediatric kidney transplantation

  • 期刊论文

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  • 发表日期：

    2025年7月21日

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  • Maral Baghai Arassi,
  • Nora Fisch,
  • Manuel Feißt,
  • Kai Krupka,
  • Britta Höcker,
  • Alexander Fichtner,
  • Nele Kanzelmeyer,
  • Jens König,
  • Anette Melk,
  • Jun Oh,
  • Lars Pape,
  • Lutz T. Weber,
  • Marcus Weitz,
  • Burkhard Tönshoff

摘要

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.

Graphical Abstract