HIGH tacrolimus intrapatient variability (IPV) was associated with increased risks of graft loss and rejection following kidney transplantation, according to a systematic review and meta-analysis of 11,647 adult kidney transplant recipients. The findings highlight the potential significance of fluctuations in tacrolimus exposure when assessing long term transplant outcomes, although further evidence is needed before variability can be adopted as a standard clinical monitoring tool.
Tacrolimus IPV has been proposed as a predictor of adverse outcomes after kidney transplantation, but uncertainty has remained regarding the strength and consistency of this association across different measurement methods. To investigate this, researchers conducted a systematic review and meta-analysis of cohort studies examining tacrolimus IPV and clinical outcomes in adult kidney transplant recipients.
The analysis included 10 studies identified through searches of MEDLINE, CENTRAL, Scopus, and Embase, covering evidence published up to October 2025. The primary outcome was death censored graft loss. A random effects meta-analysis using a three-level model accounted for the dependence of multiple effect estimates within individual studies.
High tacrolimus IPV was associated with more than twice the risk of death censored graft loss (hazard ratio: 2.13; 95% confidence interval: 1.37–3.32). The analysis also identified an association with rejection (hazard ratio: 2.05; 95% confidence interval: 1.24–3.41).
However, the findings showed considerable variability between studies for graft loss, with an I² value of 69.3%. By contrast, heterogeneity for rejection was 0.0%, indicating greater consistency in the reported effect estimates for this outcome.
The reported prevalence of high tacrolimus IPV ranged from 11% to 69%. Differences in the metrics used to calculate variability, the thresholds applied and the periods assessed may explain this wide range. Point estimates remained similar across measurement methods, geographical regions and assessment timeframes, although these subgroup analyses were exploratory and imprecise.
The findings suggest that tacrolimus IPV could have potential value in identifying kidney transplant recipients at increased risk of graft loss and rejection. Nevertheless, the observed associations do not establish that variability directly causes these outcomes or that monitoring IPV would improve clinical results.
Before tacrolimus IPV can be implemented as a reliable clinical monitoring tool, researchers emphasised the need for standardised measurement methods and validated thresholds. Prospective evidence will also be required to establish its practical value in clinical care.
For healthcare professionals involved in kidney transplantation, the findings identify tacrolimus variability as a potentially important area for further investigation. Establishing consistent approaches to measuring IPV and determining its predictive value could help clarify whether it can meaningfully support the assessment of transplant outcomes.
Reference
Chienwichai K et al. High tacrolimus intrapatient variability is associated with graft loss after kidney transplantation: a systematic review and meta-analysis. Sci Rep. 2026;DOI:10.1038/s41598-026-75230-8.
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