Association between the CYP3A5*1 Allele, Tacrolimus Concentrations and Renal Function in Lung Transplant Recipients
Pharmacy, University of Colorado Hospital, Aurora, CO
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO
Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO
Meeting: 2013 American Transplant Congress
Abstract number: B904
Dose-adjusted tacrolimus (TAC) trough levels (ng/ml per mg/day, L/D) are significantly lower in lung transplant recipients (LTxR) who are CYP3A5 expressors (*1/*1 or *1/*3) versus non-expressors (*3/*3). This may result in higher TAC dosing and peak levels. Since TAC exposure is linked to renal insufficiency, we sought to determine if glomerular filtration rate (eGFR) differed between LTxR who possess the CYP3A5*1 allele versus those who do not.
LTxR on TAC were included in this cross-sectional study. The primary outcome was the difference in estimated eGFR (MDRD) between CYP3A5 *1/*1 or *1/*3 genotypes (expressors) versus the *3/*3 genotype (non-expressors). eGFR was also compared between LTxR who had a low TAC L/D (at or below median) and high TAC L/D (above median). Trough TAC levels were assessed at the time of sample collection for genotyping. The Mann-Whitney U test was used to compare continuous variables between groups.
The study included 10 CYP3A5 expressors (all *1/*3) and 41 non-expressors (*3/*3). Median TAC L/D was 1.3 ng/mL per mg/day. CYP3A5 expressors had a significantly lower TAC L/D and eGFR than non-expressors (Table). All 10 expressors had a low TAC L/D. There were no significant differences in age, sex, weight, time post-LTx, race, or interacting medications (i.e., diltiazem) between expressors and non-expressors.
| Expressor n=10 | Non-expressor n=41 | p | Low TAC L/D n=26 | High TAC L/D n=25 | p | |
| Age | 61 ± 10 | 60 ± 10 | 0.7 | 63 ± 7 | 56 ± 11 | 0.04 |
| Sex (F) | 6 (60%) | 15 (37%) | 0.3 | 12 (46%) | 9 (36%) | 0.8 |
| Weight (kg) | 75 ± 21 | 75 ± 16 | 0.7 | 76 ± 20 | 73 ± 12 | 0.4 |
| Time post-LTx (years) | 4.6 ± 4.1 | 4.1 ± 2.5 | 1.0 | 3.4 ± 3 | 5.0 ± 2.5 | 0.01 |
| TAC dose (mg/day) | 2.5 ± 2.3 | 1.3 ± 1.0 | 0.2 | 2.0 ± 1.8 | 1.1 ± 0.5 | 0.1 |
| TAC level (ng/mL) | 1.4 ± 1.3 | 2.3 ± 1.6 | 0.04 | 1.5 ± 1.3 | 2.8 ± 1.6 | < 0.001 |
| TAC L/D (ng/mL per mg/day) | 0.6 ± 0.3 | 2.0 ± 1.4 | < 0.001 | 0.9 ± 0.3 | 2.7 ± 1.3 | < 0.001 |
| Scr (mg/dL) | 1.7 ± 0.8 | 1.3 ± 0.3 | 0.09 | 1.5 ± 0.5 | 1.3 ± 0.3 | 0.01 |
| eGFR (mL/min/1.73m2) | 40 ± 13 | 53 ± 15 | 0.02 | 44 ± 11 | 57 ± 17 | 0.004 |
In this univariate analysis, eGFR was lower in CYP3A5 expressors, and those with a low TAC L/D versus their respective comparator groups. This could be secondary to higher levels of toxic TAC metabolite
To cite this abstract in AMA style:
Schoeppler K, Kiser T, Aquilante C, Fish D, Zamora M. Association between the CYP3A5*1 Allele, Tacrolimus Concentrations and Renal Function in Lung Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/association-between-the-cyp3a51-allele-tacrolimus-concentrations-and-renal-function-in-lung-transplant-recipients/. Accessed November 22, 2024.« Back to 2013 American Transplant Congress