Impact of tacrolimus trough level variability on graft outcomes in low-immunological risk kidney transplantation

Abstract

Tacrolimus is the foundation of maintenance immunosuppression post renal transplantation, but its small therapeutic index and intra-patient variability (IPV) can affect the graft prognosis. The effect of early tacrolimus IPV in low immunological risk living-donor recipients is not clearly defined yet. We aimed to determine the association between early tacrolimus IPV with renal allograft outcomes in low-risk living donor recipients. The present single-center prospective trial used 95 adult low-risk living-donor kidney transplant recipients as their test subjects, with a 12-month follow-up time. The tacrolimus trough levels were determined as per the institutional protocol and IPV was determined as the coefficient of variation (CV%) of trough levels recorded by month 1 onwards. The primary outcome was the estimated glomerular filtration rate (eGFR) after 12 months; the secondary outcomes were Doppler-derived resistive index (RI), renal strain elastography, and indicated biopsy results. Greater tacrolimus IPV had a significant, albeit weak, relationship with a reduced eGFR at 12 months (r = -0.22, <i>p</i> = 0.033). Directional tendencies of increased RI and stiffness of the grafts were detected but not at the level of statistical significance. No significant correlation was observed between IPV and biopsy-proven rejection but only a small number of biopsy was obtained. Higher tacrolimus variability was linked with reduced early graft function in this low-risk cohort. Although causality cannot be inferred, exposure instability may represent a relevant marker of graft performance. Larger multicenter studies are needed to confirm its clinical utility.