Effects of tacrolimus intrapatient variability and CYP3A5 polymorphism on the outcomes of pediatric kidney transplantation.

Abstract

The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long-term outcome of kidney transplantation. The CYP3A single-nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. The group with high IPV had a significantly higher rate of de novo donor-specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p=.003). The high IPV group also had a higher incidence of T-cell-mediated rejection (TCMR; p<.001). The high IPV had no significant influence on Epstein-Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p=.003). Overall, the graft survival rate was inferior in the high IPV group (p<.001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR-free survival rate (p<.001). The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac.