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

Abstract

Tacrolimus intrapatient variability (IPV) has been proposed as a predictor of adverse outcomes after kidney transplantation, but the magnitude and consistency of this association across IPV measurement methods remain unclear. We conducted a systematic review and meta-analysis of cohort studies evaluating the association between tacrolimus IPV and clinical outcomes in adult kidney transplant recipients. MEDLINE, CENTRAL, Scopus, and Embase were searched from inception through October 2025. The primary outcome was death-censored graft loss (DCGL). Random-effects meta-analyses used a three-level model to account for dependence among multiple effect sizes within studies. Ten studies involving 11,647 patients were included. High tacrolimus IPV was associated with increased risk of DCGL (HR 2.13, 95% CI 1.37–3.32; I2 = 69.3%) and rejection (HR 2.05, 95% CI 1.24–3.41; I2 = 0.0%). Point estimates were similar across IPV calculation methods, geographic regions, and assessment timeframes, although subgroup analyses were exploratory and imprecise. The reported prevalence of high IPV ranged from 11 to 69%, reflecting differences in the variability metric, threshold, and measurement window. Taken together, high tacrolimus IPV is associated with graft loss and rejection after kidney transplantation. Whether IPV can serve as a clinical monitoring tool will require standardized measurement, validated thresholds, and prospective evidence.

The authors' abstract, as published at the source. Scientific Reports, 2026 · DOI ↗