Background: Subtherapeutic tacrolimus trough concentrations are associated with donor specific antibody (DSA), acute rejection and shortened graft survival. The role of intrapatient variability in tacrolimus trough variability on graft outcomes is unclear.

Aim: To determine the effect of tacrolimus variability on DSA development, acute rejection, and graft outcomes in pediatric renal transplant recipients.

Methods: Single-center cohort of pediatric kidney recipients. Intrapatient tacrolimus variability was defined using the coefficient of variation (CV; defined as SD/Mean) for any values obtained after 3 months post-transplant. CV cutpoints of 30%, 40% and 50% were used in analyses. Patients on non-tacrolimus regimens were excluded.

Results: 52 (38.5% Hispanic, 29.9% African American (AA), 9.6% Caucasian and 23.1% Other) patients were included in our final analyses. The population median age was 12 years (6.3, 15.3). The median CV was 46% (35%,58%). Using CV cutpoints of 30% and 40%; DSA development, rejection and higher urinary tract infections (UTI) were associated with a higher CV but not graft function or loss.

AA race was significantly associated with a CV of ≥40% (p=0.007) and 50% (p=0.007) but not 30% (p=0.36). A CV ≥50% was associated with a higher frequency of de novo DSA. A CV ≥50% was associated a significantly UTI. A higher CV was associated a trend towards a significantly lower GFR at 1 and 3 years post-transplant. There were no differences in donor or recipient characteristics aside from Class I PRA [figure 1] When CV was used as a continuous variable, there was a significant correlation between increasing tacrolimus variability and GFR (r=-0.36; p=0.01). Graft loss was significantly higher if the CV was ≥50% (p=0.02) but not with the other CV cut offs.

Conclusion: African Americans demonstrated significantly more tacrolimus variability when compared to other racial groups. High intrapatient tacrolimus variability is associated with de novo DSA, rejection, UTI, lower GFR and a higher frequency of graft loss. Adding the assessment of tacrolimus variability to current monitoring methods is an important step towards improving graft outcomes.

CITATION INFORMATION: Solomon S., Del Rio M., Colovai A., Hayde N. High Tacrolimus Variability is Associated with Worse Outcomes in Pediatric Renal Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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