Tacrolimus variability score outperforms coefficient of variation in predicting clinical outcomes of living kidney transplantation

Intrapatient variability (IPV) was previously defined as coefficient of variation (CV) or standard deviation of tacrolimus (Tac) exposure while none of them was easily being interpreted and translated into clinical practice after kidney transplantation.We developed a novel Tac variability score (TVS) to evaluate IPV by calculating the frequency of clinically significant changes of Tac trough levels after kidney transplantation. Multivariate Cox proportional analyses were conducted to compare the impact of TVS and CV on transplant outcomes.A total of 1343 patients were divided into high TVS (0.30) and low TVS (0.30) groups, and low CV (0.30) and high CV (0.30) groups. Univariate analyses showed that high TVS (hazard ratio [HR]: 2.323, 95% confidence interval [CI]: 1.455-3.709) and high CV (HR: 1.606, 95%CI: 1.044-2.471) were associated with inferior graft survival. However, only TVS was an independent predictor for graft failure in multivariate analyses (HR: 1.972, 95%CI: 1.2-3.24), and the correlation maintained in high CV (P = .020) and low CV (P = .037) subgroups, while CV failed to predict graft loss in neither low (P = .387) nor high TVS (P = .600) subgroups. In addition, TVS had a higher correlation with graft survival in patients with Tac exposure within the therapeutic range and the correlation was less influenced by mean Tac trough levels.TVS is a novel measure of Tac IPV with higher correlation with graft survival and more convenience in clinical use than CV after kidney transplantation.