Early CYP3A5 Genotype-Based Adjustment of Tacrolimus Dosage Reduces Risk of De Novo Donor-Specific HLA Antibodies and Rejection among CYP3A5-Expressing Renal Transplant Patients

被引:0
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作者
Schoenfelder, Kristina [1 ]
Moehlendick, Birte [2 ]
Eisenberger, Ute [1 ]
Kribben, Andreas [1 ]
Siffert, Winfried [2 ]
Heinemann, Falko M. [3 ]
Gaeckler, Anja [1 ]
Wilde, Benjamin [1 ]
Friebus-Kardash, Justa [1 ]
机构
[1] Univ Duisburg Essen, Univ Hosp Essen, Dept Nephrol, D-45147 Essen, Germany
[2] Univ Duisburg Essen, Univ Hosp Essen, Inst Pharmacogenet, D-45147 Essen, Germany
[3] Univ Duisburg Essen, Univ Hosp Essen, Inst Transfus Med, Transplantat Diagnost, D-45147 Essen, Germany
关键词
tacrolimus dosage; tacrolimus trough levels; anti-HLA antibodies; DSAs; renal transplant rejection; renal transplant; calcineurin inhibitor nephrotoxicity; TROUGH LEVELS; PHARMACOGENETICS; IMPLEMENTATION; POLYMORPHISMS; METAANALYSIS; ASSOCIATION; GUIDELINES; VARIANTS; EFFICACY; TRIAL;
D O I
10.3390/diagnostics14192202
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background/Objectives: Our previous retrospective single-center cohort study found, at 3-year follow-up, a trend toward low tacrolimus trough levels and an increased risk of de novo donor-specific anti-HLA antibodies (DSAs) and of antibody-mediated rejection (ABMR) in CYP3A5-expressing patients. Determining CYP3A5-expression status immediately after renal transplant would allow early genotype-based dosage adjustment of tacrolimus and might prevent the occurrence of de novo DSAs and ABMR, improving transplant outcome. Methods: 160 renal allograft recipients who underwent renal transplant at the University Hospital Essen between May 2019 and May 2022 were genotyped for the CYP3A5 rs776746 polymorphism within the first two weeks after transplant, and genotype-based dose adjustment of tacrolimus was performed for the follow-up of 2 years. Results: CYP3A5 expression was detected in 33 (21%) of the 160 patients. Tacrolimus trough levels were similar in CYP3A5 expressers and nonexpressers over the entire 2-year follow-up period. However, we observed a trend toward slightly higher tacrolimus trough levels in CYP3A5 expressers, who, as expected, required tacrolimus dosages twice as high as did nonexpressers during follow-up. Calcineurin inhibitor (CNI) nephrotoxicity-free survival rates were comparable between CYP3A5 expressers and nonexpressers (p = 0.49). Rejection-free survival rates (p = 0.89), de novo anti-HLA antibody-free survival rates (p = 0.57) and de novo DSA-free survival rates (p = 0.61) did not differ between the two groups. Conclusions: Early detection of CYP3A5-expression status and resultant genotype-based adjustment of tacrolimus dosage after renal transplant protected patients from transplant rejection and de novo DSA formation and was not associated with increased incidence of CNI toxicity among CYP3A5 expressers.
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页数:16
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