Anam Sutewala1,2, Rachael Kermond1,2, Anne Durkan1,2, Deirdre Hahn1,2, Deborah Lewis1,2, Hugh McCarthy1,3, Stephen Alexander1,3, Siah Kim3,4
1Department of Nephrology, The Children’s Hospital At Westmead, Westmead, Australia, 2The Children’s Hospital at Westmead Clinical School, Sydney University, Westmead, Australia , 3Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Australia, 4Sydney School of Public Health, Sydney University, Camperdown, Australia
Background: Adequate immunosuppression is essential for long term graft outcomes after kidney transplantation (KT). High intra-patient variability (IPV) in tacrolimus trough levels (TTL) is associated with acute rejection, graft loss, and de novo donor-specific antibody (dnDSA) development in adult KT recipients (KTR).
Aim: Our study aimed to determine the effect of tacrolimus IPV on acute rejection and dnDSA development in paediatric kidney transplant recipients (KTR).
Methods: This retrospective cohort study evaluated paediatric KTR at The Children’s Hospital at Westmead. We collected TTL one to five years post KT and calculated coefficient of variance (CV = standard deviation/mean x 100). We examined its association with acute rejection and dnDSA development using Cox-proportional hazard models.
Results: Thirty paediatric KTR (16 males; 54%) with a mean age of 6.0 (s.d.) (4.0) years were included. Of 28 patients, acute graft rejection occurred in 6 patients (21%). The mean tacrolimus CV was 43%(18.6%) compared to 30%(8.1%) in patients who did not experience acute rejection. Univariate cox-proportional hazards model found a 1% increase in tacrolimus IPV resulted in a 7% increased risk of acute rejection (HR: 1.07, 95% CI: 1.02–1.14). dnDSA were detected in 13 (48%) of 27 patients. The mean tacrolimus CV was 36% (16%) compared to 28%(8.3%) in patients who did not develop dnDSA. Univariate cox-proportional hazards models found a 1% increase in tacrolimus IPV resulted in a 3.0% increased risk of dnDSA development (HR: 1.03, 95% CI: 0.99–1.07).
Conclusion: Acute rejection in paediatric KTR is associated with increased levels of tacrolimus IPV. An association between development of dnDSA and high tacrolimus IPV was not demonstrated in this study.
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