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Abstract: PO2539

High Intrapatient Variability of Tacrolimus in Pediatric and Adolescent Renal Transplant Recipients Is Associated with Worse Graft Outcomes

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Piburn, Kim H., Stanford University School of Medicine, Stanford, California, United States
  • Maestretti, Lynn K., Lucile Salter Packard Children's Hospital at Stanford, Palo Alto, California, United States
  • Patton, Mary Victoria, Lucile Salter Packard Children's Hospital at Stanford, Palo Alto, California, United States
  • Mcgrath, Anne Marie, Lucile Salter Packard Children's Hospital at Stanford, Palo Alto, California, United States
  • Shetty, Rajesh R., Lucile Salter Packard Children's Hospital at Stanford, Palo Alto, California, United States
  • Chaudhuri, Abanti, Stanford University School of Medicine, Stanford, California, United States
  • Grimm, Paul C., Stanford University School of Medicine, Stanford, California, United States
  • Sigurjonsdottir, Vaka Kristin, Stanford University School of Medicine, Stanford, United States
Background

High intra-patient variability (IPV) in tacrolimus (TAC) levels has been associated with the development of de novo donor-specific antibodies. The degree of TAC IPV in relation to poor graft outcomes in pediatric kidney transplant patients is unknown.

Methods

Patients ages 0-25 years who were transplanted from 01/01/2010-01/01/2018 at a single center were considered for inclusion. Minimum required follow-up time was 12 months. Primary outcomes were formation of C1q+ de novo DSAs (dnDSAs) and graft loss. dnDSAs were identified by routine screening or at investigation of allograft dysfunction. TAC IPV was determined using the mean coefficient of variation (CV) over the immediate 6-month time period prior to each TAC level. All available TAC levels were included in the analysis. Mean CV was calculated using CV from 10 months post-transplant until end of follow-up. Patients were followed until 01/03/2019 or until graft loss. Analyses were performed using descriptive statistics and the Mann-Whitney U test.

Results

225 pediatric kidney transplant patients met inclusion criteria. Median age was 12.5 years (range 15 mo.-21 yrs.). 46% were female, and 24% received a living donor transplant. 51 formed C1q+ dnDSA, and 174 did not. Among patients who formed C1q+ dnDSA, 13/51 (25.5%) lost their graft, compared to 2/174 (1.1%) in patients who did not form dnDSA by C1q. C1q+ dnDSA formers had higher mean CVs compared to patients who did not form dnDSA by C1q (median CV 33.9% vs 26.1%, p<0.0001), including when stratified by age subgroups of 0-12 years (p=0.0217) and 13-25 years (p=0.0001) [Figure 1]. Patients with graft loss had higher mean CVs compared to those who did not have graft loss (median CV 39.0% vs 25.8%, p=0.0006).

Conclusion

High tacrolimus IPV was associated with C1q+ dnDSA formation and graft loss. Tacrolimus IPV is a potential prognostic tool for optimizing transplantation outcomes.