Transplant Trial Watch

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.

Andrews LM, de Winter BCM, et al.

Transplantation Direct 2017; 3(2): e129.


Aims
To investigate whether a Tacrolimus (Tac) starting dose based on bodyweight leads to the achievement of Tac target whole-blood predose concentrations (C0) in overweight patients on day 3 after transplantation.

Interventions
Participants were randomized to receive Tac in either the standard, bodyweight-based dose of 0.20 mg/kg per day, versus a dose based on their CYP3A5 genotype. CYP3A5 expressers received 0.30 mg/kg per day, whereas the nonexpressers received 0.15 mg/kg per day.

Participants
203 kidney transplant recipients who participated in a previous randomized-controlled trial* who had Tac C0 available on day 3 after transplantation.

Outcomes
The primary outcome measured was Tac C0. Other outcomes measured were Tac overexposure, Tac underexposure and Tac on target.

Follow-up
Day 3

CET Conclusions
This paper represents a post hoc analysis of a previously published RCT, which had studied the interaction between CYP3A5 genotype and Tacrolimus clearance. This study aimed to investigate the relationship between bodyweight and Tacrolimus dose-response in overweight patients when commenced on bodyweight-calculated Tacrolimus dose. In the standard dosing group, overweight and obese patients had a significantly higher trough Tacrolimus level on Day 3. In fact, the median serum level was 15ng/ml, with 60% of these patients overexposed to Tacrolimus. The authors used their calculations to develop a dosing guideline considering BMI and CYP3A5 genotype, which was subsequently validated in another cohort. The new dosing guideline reduced the proportion of overexposed higher BMI patients significantly. This study is important with the increase in global obesity, however the population included were overwhelmingly of white ethnic origin, and the target Tacrolimus level may be considered high in some units (10-15ng/ml).

Jadad score
3

Data analysis
Modified intention-to-treat analysis

Allocation concealment
Yes

Quality notes
Previously assessed as *Shuker N, et al. A Randomized controlled trial comparing the efficacy of CYP3A5 genotype-based with body-weightbased tacrolimus dosing after living donor kidney transplantation. Am J Transplant. 2016;16:2085–2096.

Trial registration
None

Funding source
Not reported