Review links higher tacrolimus variability with kidney graft loss
Among adult kidney transplant recipients, greater changes in tacrolimus blood levels were associated with graft loss and rejection, but prospective studies are still needed.
Moderate evidenceReviewSome caution advised
Medical disclaimer: This article summarizes research findings and is for informational purposes only. It is not medical advice.
Editorial illustration — not from the study.
Researchers combined results from studies of adult kidney transplant recipients taking tacrolimus-based immunosuppressive regimens. Most of the studies were retrospective, and each used its own method and threshold to define high variability in tacrolimus levels.
Higher tacrolimus variability was associated with more than twice the risk of death-censored graft loss and rejection in the pooled analyses. However, the results differed in precision across analyses, and the researchers said that standardized measures, agreed thresholds, and prospective research are needed before variability can be evaluated as a clinical monitoring tool.
The question reviewed
The researchers conducted a systematic review and meta-analysis of cohort studies involving adults aged 18 or older who had received a kidney transplant and were taking tacrolimus-based treatment. They searched four medical databases through October 2025 and included 10 studies with 11,647 participants: nine retrospective cohort studies and one prospective cohort study. The main outcome was death-censored graft loss, meaning permanent loss of kidney graft function that was assessed without counting deaths as graft losses. Other outcomes included rejection, development of donor-specific antibodies, mortality, and the reported prevalence of high tacrolimus variability. The studies used several measures of variability, including the coefficient of variation, standard deviation, time-weighted coefficient of variation, mean absolute deviation, and a tacrolimus variability score.
What the review concluded
In the pooled analysis, high tacrolimus variability was associated with a higher risk of death-censored graft loss: hazard ratio 2.13, with a 95% confidence interval of 1.37 to 3.32. It was also associated with a higher risk of rejection: hazard ratio 2.05, with a 95% confidence interval of 1.24 to 3.41. The reported prevalence of high variability ranged from 11% to 69%, largely because studies used different measures, thresholds, and time periods. Results for mortality were based on only two studies and were too imprecise to support a conclusion. The associations do not establish that tacrolimus variability caused graft loss or rejection.
Where this may apply
These findings may apply to adults who have received a kidney transplant and are taking tacrolimus-based immunosuppressive regimens, particularly populations resembling those represented in the included studies. They should not automatically be applied to children, people with multiorgan transplants, people not taking tacrolimus, or other transplant populations because those groups were not evaluated here. The findings also do not by themselves establish a monitoring threshold or a beneficial intervention.
The significance
Kidney transplant recipients were the population studied, so the findings are directly relevant to understanding factors associated with transplant outcomes in that group. The analysis suggests that changes in tacrolimus levels may be a useful subject for further research, but it does not establish that measuring or reducing variability improves outcomes. The researchers specifically identified the need for standardized measurement, validated thresholds, and prospective evidence.
Limitations & evidence assessment
Most included studies were retrospective cohort studies, so differences between people with higher and lower tacrolimus variability could have contributed to the results. The studies used different variability measures, thresholds, and measurement windows, and the reported prevalence varied widely. There was substantial heterogeneity for the main graft-loss outcome, while subgroup analyses were exploratory and imprecise. Only two studies contributed to the mortality analysis, which was too uncertain to interpret. The researchers also noted that the estimate of between-study variation was imprecise because only seven studies contributed to that analysis. As an observational evidence base, the review shows associations rather than causation, and it does not show that changing tacrolimus variability improves graft outcomes.
Why this evidence level: This was a systematic review and meta-analysis of 10 cohort studies involving 11,647 adult kidney transplant recipients. The results were consistent with an association, but most included studies were retrospective and the researchers reported important differences in how tacrolimus variability was measured.
Evidence levels are editorial estimates derived from study metadata — they are not clinical appraisals.
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