Meta-analysis links high tacrolimus variability with kidney graft loss and rejection

A systematic review and meta-analysis of cohort studies found that high tacrolimus intrapatient variability was associated with death-censored graft loss and rejection among adult kidney transplant recipients. The review, reported in Scientific Reports, included 10 studies involving 11,647 patients.

Researchers searched MEDLINE, CENTRAL, Scopus and Embase from database inception through October 2025. The primary outcome was death-censored graft loss, and random-effects meta-analyses used a three-level model to account for dependence among multiple effect sizes reported within studies. Based on the supplied abstract, the pooled association between high tacrolimus intrapatient variability and death-censored graft loss was a hazard ratio of 2.13 (95% confidence interval, 1.37–3.32), with substantial heterogeneity across studies indicated by an I² value of 69.3%.

High variability was also associated with rejection, with a pooled hazard ratio of 2.05 (95% confidence interval, 1.24–3.41) and no detected heterogeneity for that outcome (I² = 0.0%). Point estimates were similar across intrapatient-variability calculation methods, geographic regions and assessment timeframes. However, the subgroup analyses were exploratory and imprecise, so those comparisons should not be treated as definitive evidence of equivalence.

The reported prevalence of high intrapatient variability ranged from 11% to 69%. The abstract attributes this variation to differences in the variability metric, threshold and measurement window, illustrating how the studies defined and measured the exposure. The analysis is limited to observational cohort evidence, and the observed associations do not establish that variability causes graft loss or rejection. The authors stated that whether intrapatient variability can serve as a clinical monitoring tool will require standardized measurement, validated thresholds and prospective evidence.

Subject of Research: Association of tacrolimus intrapatient variability with graft loss and rejection in adult kidney transplant recipients

Article Title: High tacrolimus intrapatient variability is associated with graft loss after kidney transplantation: a systematic review and meta-analysis

Article References: Chienwichai, K., Mongkolrattanakul, P., & Chang, A. (2026). High tacrolimus intrapatient variability is associated with graft loss after kidney transplantation: a systematic review and meta-analysis. Scientific Reports. https://doi.org/10.1038/s41598-026-75230-8

Image Credits: AI Generated

DOI: 10.1038/s41598-026-75230-8

Keywords: tacrolimus, kidney transplantation, intrapatient variability, graft loss, rejection, systematic review, meta-analysis, cohort studies, immunosuppression, High, intrapatient, variability