Introduction:
Tacrolimus, is a calcineurin inhibitor, used as an immunosuppressive, post renal transplant. The dosing of tacrolimus is usually done, based on the body weight as well as CYP3A5 genotyping. It has been studied that expressors (CYP3A5*1/1, *1/3) require higher doses of the drug in view of faster metabolism. However, the CYP3A5*3/3 is known to require lower doses. In view of the higher dosing required in expressors, it is postulated that they develop more complications, especially tacrolimus related complications, including post transplant diabetes mellitus.
Concentration to dose ratio (C0/D ratio) is a useful marker as studied in previous studies and ascertained that those with C0/D <1.5, tend to develop more complications, due to the requirement of higher tacrolimus dose to maintain the concentrations. So, we need to study the association of CYP3A5 genotyping and C0/D with regards to the development of post transplant diabetes mellitus (PTDM).
AIM: To study the association of CYP3A5 genotyping (expressors or non-expressors) and Concentration to dose ratio (C0/D) with the development of Post transplant diabetes mellitus.
Methods:
It is a retrospective study in which, all the patients who underwent renal transplant in our centre from 2019 to 2023, in whom CYP3A5 genotyping was done, pre-transplant were analysed. The patients were routinely given triple immunosuppression, including tacrolimus, mycophenolate mofetil and steroid. The basic demographic details were analysed.
Based on the CYP3A5 genotyping, the patients were grouped into expressors and non-expressors (CYP3A5 1/1,1/3 and 3/3,respectively). Tacrolimus level at day 3, post transplant and daily tacrolimus dose were studied.
Concentration to dose ratio (C0/D) was calculated by dividing tac level at day 3 by the daily dose at day 3 and is expressed as ng/ml/mg. C0/D ratio is categorized into those with <1.5 and those with ≥1.5.
The data was analysed for the association of CYP3A5 genotyping and C0/D ratio with the development of PTDM.
Results:
A total of 89 post renal transplant patients were included in the study, among which 34.83% were females and 65.17% were males (n=31and 58 respectively). Mean age of the subjects was 37.71±12.8 years, with median (25th-75th percentile) of 37 (28-49)years (fig 1). On categorising the patients into expressors and non- expressors, there were 47 (52.81%) of expressors and 42 (47.19%) of non- expressors (table 2). Among the C0/D values, 55 (61.80%) had C0/D of ≥1.5, while 34 (38.20%) had C0/D of <1.5. Mean value of C0/D among the study subjects was 2.22±1.34. with median of 2 (1.16-2.98).
On studying the distribution of complications among the expressors and non expressors, there was a comparable distribution of tacrolimus related complications, including post transplant diabetes mellitus among the two groups, which included 26.19% in non-expressors vs. 38.30% in expressors with p value of 0.224 (table 3)
Among the distribution of post transplant diabetes mellitus with C0/D, it was observed that there was a non significant distribution with 35.29% vs 30.19 % in patients with C0/D <1.5 and ≥1.5, respectively (p value-0.571).
Conclusions:
• The CYP3A5 genotyping characterized by expressors or non-expressors, is not associated with the development of PTDM.
• On the other hand, Concentration to dose ratio (C0/D) also, does not show a significant association with the development of PTDM.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.