High intrapatient variability of tacrolimus concentrations predicts accelerated progression of chronic histologic lesions in renal recipients

High intrapatient variability (IPV) of tacrolimus concentrations is increasingly recognized as a predictor of poor outcome in solid organ recipients. How it relates to evolution of histology has not been explored. We analyzed tacrolimus IPV using coefficient of variability (CV) from months 6-12 posttransplant in a cohort of 220 renal recipients for whom paired protocol biopsies at 3 months and 2 years were available. Recipients in the highest CV tertile had an increased risk of moderate to severe fibrosis and tubular atrophy by 2 years compared with the low IPV tertile (OR 2.47 [1.09-5.60], p = 0.031 and OR 2.40 [1.03-5.60], p = 0.043, respectively). Other predictors were donor age, severity of chronic lesions at 3 months and presence of borderline or subclinical rejection at 3 months. Chronicity score increased significantly more in the high CV tertile group than in the middle and low tertiles (mean increase 1.97 ± 2.03 vs. 1.18 ± 2.44 and 1.12 ± 1.80, respectively; p < 0.05). CV did not predict evolution of renal function, which did not deteriorate within the 2-year follow-up period. These results indicate that high IPV is related to accelerated progression of chronic histologic lesions, before any evidence of renal dysfunction. This article is protected by copyright. All rights reserved.