Transplant Trial Watch

A Randomized controlled trial comparing the efficacy of CYP3A5 genotype-based with bodyweight-based tacrolimus dosing after living donor kidney transplantation.

Shuker N, Bouamar R, et al.

American Journal of Transplantation 2016;16(7):2085-96

To investigate whether CYP3A5 genotype-based Tacrolimus (Tac) dosing leads to earlier achievement of Tac target whole-blood exposure and therefore an increase in clinical outcomes after kidney transplantation.

Patients were randomized to receive either Tac in a standard, bodyweight-based dose of 0.2 mg/kg/day, or a dose determined by their CYP3A5 genotype.

240 living-donor renal transplant recipients aged ≥ 18 years

The primary measured outcome was the proportion of patients within the desired Tac whole-blood range. Secondary measured outcomes included the average Tac predose concentration(Co), time required to reach the target Co range, number of Tac dose modifications needed to reach the target Co range, number of markedly sub-therapeutic Tac and markedly supra-therapeutic Co measurements, delayed graft function, biopsy-proven acute rejection, clinically presumed acute rejection, and renal function.

3 months

CET Conclusions
Kidney transplant recipients expressing the CYP3A5 gene need a higher tacrolimus dose than non-expressers to reach therapeutic exposure. This interesting and well-written report of 240 living donor kidney recipients investigated whether a tacrolimus starting dose based on CYP3A5 genotype leads to earlier achievement of target tacrolimus concentrations compared to a starting dose based on bodyweight. A power analysis showed that 196 patients were needed to achieve a power of 80%. The randomisation sequence was computer-generated and allocation to groups was adequately concealed. The proportion of patients reaching the desired therapeutic tacrolimus dose was similar in the two groups at 3 days posttransplant as was the proportion of patients with sub- or supra-therapeutic tacrolimus concentrations. Clinical outcomes between groups were also similar. The authors correctly conclude that routinely genotyping renal transplant candidates for CYP3A5 cannot be recommended based on these data.

Jadad score

Data analysis
Modified intention-to-treat analysis

Allocation concealment

Trial registration
Dutch National Trial Registry - NTR2226

Funding source
Non-industry funded