Background: High intrapatient variability (IPV) of tacrolimus (Tac) is increasingly recognized as a risk factor for poor graft outcomes in kidney transplantation. The timing of onset of its impact on kidney histologic lesions has not been investigated.
Methods: We analyzed the adverse effect of Tac IPV using the coefficient of variability from 6 to 12 months posttransplantation on long-term outcomes in a cohort of 671 kidney recipients and on the evolution of chronic histologic lesions in a cohort of 212 recipients for whom paired protocol biopsies at 10 days and 1 year were available.
Results: High IPV of Tac (cutoff value of coefficient of variability = median of 20.5%) was associated with an increased risk of graft loss (hazard ratio, 3.28; 95% confidence interval, 1.090-9.849; P = 0.035) in the entire cohort. At 1 year, the high Tac IPV group showed a significantly deteriorated chronicity score (F = 5.912, P = 0.016) compared with the low Tac IPV group in the Histology cohort after controlling for the 10-day scores. In a multivariate analysis, a high IPV of Tac was predictive of the chronicity score (odds ratio, 1.91; 95% confidence interval, 0.215-1.075; P = 0.003) at 1 year posttransplant.
Conclusions: These data indicate that high IPV of Tac is associated with early deterioration of chronic histologic lesions as well as poorer long-term outcomes. Large prospective studies of Tac IPV usage as a clinical monitoring tool are needed in the future.