CYP3A5 genotyping-guided dosing versus weight-based dosing in a multi-ethnic population of kidney transplant recipients
Introduction Tacrolimus is the cornerstone of immunosuppression after kidney transplantation (KTx) and is characterized by a narrow therapeutic index and large inter-individual variability. Pre-transplant CYP3A5 genotyping to guide tacrolimus dosing may help achieve target levels more rapidly and im...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2025-07-01
|
| Series: | Proceedings of Singapore Healthcare |
| Online Access: | https://doi.org/10.1177/20101058251365300 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Introduction Tacrolimus is the cornerstone of immunosuppression after kidney transplantation (KTx) and is characterized by a narrow therapeutic index and large inter-individual variability. Pre-transplant CYP3A5 genotyping to guide tacrolimus dosing may help achieve target levels more rapidly and improve outcomes, but its impact remains unclear in our local multiethnic population where CYP3A5 expression may differ amongst ethnic groups. This pilot study aimed to investigate the impact of CYP3A5-guided tacrolimus dosing on target achievement after KTx in our multi-ethnic population. Methods This was a pilot single-centre study comparing CYP3A5-guided (0.20 mg/kg/day for normal and intermediate metabolizers and 0.15 mg/kg/day for poor metabolizers) with weight-based (0.10-0.20 mg/kg/day) tacrolimus dosing in living donor KTx recipients from January 2016 to June 2023. Primary outcomes were proportions of patients within target trough levels on day 3 and day 7 after tacrolimus initiation. Results The study included 51 patients (13 CYP3A5-guided, 38 weight-based). CYP3A5 expression differed between the Chinese and non-Chinese groups ( p = .02). Initial median tacrolimus dose was higher in the CYP3A5-guided group (0.16 vs 0.12 mg/kg/day, p < .001). Proportions of patients who achieved target levels did not differ between the two groups on day 3 (46.2% vs 18.4%, p = .07) and day 7 (50.0% vs 34.2%, p = .50) after tacrolimus initiation. Median days to target trough levels were shorter in the CYP3A5-guided group (5 vs 7, p = .03). Hyperkalemia (>5.5 mmol/L) was higher in the CYP3A5-guided group (53.8% vs 21.1%, p = .04). Conclusion CYP3A5 expression differed amongst ethnic groups. CYP3A5-guided tacrolimus dosing may lead to faster achievement of target trough levels but may increase risk of hyperkalemia. |
|---|---|
| ISSN: | 2059-2329 |