Efficacy and outcomes of CYP3A5 genotype-based tacrolimus dosing compared to conventional body weight-based dosing in living donor kidney transplant recipients
Indian Journal of Nephrology, ISSN: 1998-3662, Vol: 32, Issue: 3, Page: 240-246
2022
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Article Description
Introduction: Clinical use of tacrolimus has been challenging due to its narrow therapeutic index and highly variable pharmacokinetics. In this study, we compared patients who received body weight-based tacrolimus dosing pre-transplant (transplanted from 2016 to 2018) with those who received CYP3A5 genotype-based dosing (2018 to 2020). Methods: Eighty-two renal transplant recipients were non-randomly assigned to genotype-adapted or bodyweight-based tacrolimus dosing groups. The primary end point was to study the proportion of subjects who achieved the target tacrolimus C 0 on post-op day 4. Secondary end points included clinical outcomes and safety. Results: The proportion of subjects who achieved the target tacrolimus C 0 on postoperative days 4 and 10 were significantly higher in the adapted group, 53.6% and 47.5%, compared to 24.3% and 17% in controls, respectively (P = 0.01). Adapted group subjects achieved their first target tacrolimus C 0 significantly earlier (4 days) compared to 25 days in controls (P = 0.01). The total number of tacrolimus dose modifications required in the first postop month were lower in the adapted group; 47 compared to 68 in the controls (P = 0.05). The proportion of subjects with sub-therapeutic tacrolimus exposure on postoperative day 4 was significantly higher in the controls, 56% versus 10% in the adapted group (P < 0.001). There were no significant differences between the groups in the rate of biopsy proven acute rejections, adverse events, and graft function at the end of 3 months follow up. Conclusion: Genotype-based tacrolimus dosing leads to more subjects achieving the target tacrolimus C 0 earlier. However, there may be a higher risk of tacrolimus nephrotoxicity.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85132414214&origin=inward; http://dx.doi.org/10.4103/ijn.ijn_278_20; http://www.ncbi.nlm.nih.gov/pubmed/35814319; https://indianjnephrol.org/efficacy-and-outcomes-of-cyp3a5-genotype-based-tacrolimus-dosing-compared-to-conventional-body-weight-based-dosing-in-living-donor-kidney-transplant-recipients/; https://dx.doi.org/10.4103/ijn.ijn_278_20; https://journals.lww.com/ijon/fulltext/2022/32030/efficacy_and_outcomes_of_cyp3a5_genotype_based.8.aspx
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