High Intrapatient Tacrolimus Variability and Increased Cell-Free DNA in Kidney Transplant Recipients.

An inverse relationship has been identified between tacrolimus serum concentrations and donor-derived cell-free DNA (dd-cfDNA) levels after lung transplant, but limited data exists on this relationship in the kidney transplant population. The purpose of this evaluation was to examine the relationship between high tacrolimus variability and elevated dd-cfDNA levels in kidney and simultaneous pancreas-kidney transplant recipients at a single center. Single-center, retrospective, descriptive comparative evaluation of kidney and pancreas-kidney transplant recipients who received longitudinal ddcfDNA surveillance. Intrapatient tacrolimus variability was assessed using the coefficient of variation (%CV) measured between 1 and 12 months posttransplant. Pediatrics, retransplant or multiorgan transplant recipients, and pregnant recipients were excluded. One hundred fifteen recipients with 518 dd-cfDNA levels and 3028 tacrolimus troughs were assessed. Pancreas-kidney recipients had significantly higher median dd-cfDNA (0.29% vs. 0.18%,  = .034) and were excluded from analysis. Ninety-nine kidney transplant recipients were included for analysis. Recipients with tacrolimus %CV ≥30 ( = 66) had significantly higher median dd-cfDNA than %CV <30 (0.22% vs. 0.17%,  = .031). Tacrolimus %CV ≥30 demonstrated higher median peak dd-cfDNA than %CV <30, though this was not statistically significant (0.36% vs. 0.28%,  = .058). These data demonstrated that high intrapatient tacrolimus variability may be associated with elevated dd-cfDNA in the first year after kidney transplant.