Tacrolimus variability is associated with de novo donor-specific antibody development in pediatric renal transplant recipients.

backgroundDonor-specific antibody (DSA) is a risk factor for antibody-mediated rejection and shortened graft survival. We investigated the role of intrapatient variability in tacrolimus trough levels on graft outcomes (i.e., de novo DSA, rejection, graft loss) in pediatric renal transplant recipients.

methodsThis was a single-center retrospective study which included 38 pediatric renal transplant recipients. Intrapatient tacrolimus variability was defined using the coefficient of variation (CV; SD/Mean × 100) for all levels obtained after 3 months post-transplant. CV cut-points of 30%, 40%, and 50% were used in the analyses.

resultsThe median CV 43.1% (35.0%, 58.6%). Out of 38 patients, 19 (50%) developed de novo DSA. In the logistic regression model, after adjusting for age, rejection history, maintenance immunosuppression, and CV, for every 10% increase in tacrolimus variability, the odds of developing de novo DSA increased by 53% (p = 0.048, CI 1.0005, 1.11). Age at transplant was also an independent risk factor for DSA development; every 1 year increase in age was associated with a 31% increase in the odds of developing DSA (p = 0.03, CI 1.03, 1.67). At a CV cut-point ≥ 30%, higher tacrolimus variability was associated with an increased incidence of allograft rejection (0% vs 42%, < 30 and ≥ 30% respectively, p = 0.07). As there were few graft loss events (n = 4) in our study population, an association could not be determined between tacrolimus variability and graft loss.

conclusionTacrolimus variability and age at transplant were identified as independent risk factors for de novo DSA development. There was an association between tacrolimus variability and rejection in pediatric renal transplant recipients. Adding the assessment of tacrolimus variability to current monitoring methods may be an important step towards improving graft outcomes.