Session Time: 3:15pm-4:45pm
Presentation Time: 4:15pm-4:27pm
*Purpose: High intra-patient variability (IPV) in tacrolimus (TAC) levels is associated with de novo donor-specific antibodies (dnDSA) and graft loss. We examined the natural history of TAC variability in pediatric renal transplant patients and the degree of variability in relation to poor graft outcomes.
*Methods: Children transplanted from 2010-2018 at a single center were considered for inclusion. dnDSA were identified by routine screening or at investigation of graft dysfunction. Patients with follow-up time of 12+ months were included. Primary outcome was development of C1q+ dnDSA >12 months post-transplant. All TAC levels in patients age 0-25 years transplanted from 2004-2019, with 2+ levels were analyzed. IPV was determined using the coefficient of variation (CV) over a 6-month time period for each TAC level.
*Results: A total of 251 pediatric renal transplant recipients were included. Median age was 11 years (range 11 months-24 years); 46% were female, and 23% received a living donor transplant. Median follow-up time was 88 months (range 12-122). 57 formed dnDSA by C1q, and 194 did not. 22.8% of patients with dnDSA by Cq1 lost their graft. In patients without dnDSA by C1q, 2.6% lost their graft (p<0.001). For baseline CV determination among the pediatric renal transplant population, a total of 31125 TAC levels (median 64.5, range 2-428) for 426 patients were analyzed. TAC was highly variable immediately post‑transplant and plateaued by 1 year post-transplant [Figure 1]. CV varied with age [Figure 2]. Median CV for the entire population was 29.5% (range 0.54-173.2%). Median CV for patients who developed dnDSA by C1q was 48.0% (range 19.3-97.5%). CV in dnDSA formers was compared to baseline CV by age subgroups, 0-12 years and 13-25 years (p<0.0001 for both comparisons) using the Mann-Whitney test [Figure 3].
*Conclusions: High TAC IPV was associated with dnDSA formation. Understanding patterns in IPV may allow for targeted interventions to improve long-term graft survival and outcomes.
To cite this abstract in AMA style:Piburn K, Maestretti L, Shetty R, Patton MV, McGrath A, Concepcion W, Chaudhuri A, Grimm PC, Sigurjonsdottir VK. High Intra-Patient Variability of Tacrolimus in Pediatric and Adolescent Renal Transplant Recipients is Associated with Worse Graft Outcomes [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/high-intra-patient-variability-of-tacrolimus-in-pediatric-and-adolescent-renal-transplant-recipients-is-associated-with-worse-graft-outcomes/. Accessed May 18, 2021.
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