CYP3A5 Genotype Had No Influence on Renal Function after Renal Transplantation
Renal Medicine and Transplantation, St George’s University Hospitals NHS Foundation Trust, London, United Kingdom
Meeting: 2019 American Transplant Congress
Abstract number: A233
Keywords: FK506, Gene polymorphism, Immunosuppression, Kidney transplantation
Session Information
Date: Saturday, June 1, 2019
Session Name: Poster Session A: Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Tacrolimus metabolism rate has been reported to be associated with renal function after renal transplantation (Thölking et al., 2014); this study aimed to determine whether CYP3A5 genotype is a contributory factor.
*Methods: We performed a retrospective observational analysis of 295 patients who underwent renal transplantation between 1995 and 2017. CYP3A5 genotypes of *1/*1, *1/*3 or *1/*3 were determined. Serum creatinine, trough tacrolimus concentration and tacrolimus dose were recorded at day 7, day 14 and 3 months post-transplantation. Glomerular filtration rate was estimated using the CKD-EPI equation (eGFR). Groups were compared by the Kruskal-Wallis H test.
*Results:
Table 1. Mean blood tacrolimus trough concentrations, tacrolimus doses and concentration/dose ratios by CYP3A5 genotype across all time points.
| *1/*1 (n=27) | *1/*3 (n=81) | *3/*3 (n=187) | P value | |
| Tacrolimus mean concentration (ng/ml) | 10.94±4.66 | 11.73±4.29 | 13.94±6.05 | <0.0001 |
| Tacrolimus mean daily dose (mg) | 19.33±6.20 | 15.41±5.81 | 11.00±4.93 | <0.0001 |
| Mean concentration/dose ratio (ng/mL*1/mg) | 0.78±0.82 | 0.90±0.48 | 1.53±0.72 | <0.0001 |
Table 2. Mean eGFR (ml/min/1.73m2) by CYP3A5 genotype at day 7, day 14 and 3 months after renal transplantation.
| *1/*1 (n=27) | *1/*3 (n=81) | *3/*3 (n=187) | P-value | |
| Day 7 | 29.22±30.81 | 31.05±24.93 | 30.48±24.99 | 0.82 |
| Day 14 | 36.41±29.41 | 37.05±25.81 | 36.57±24.73 | 0.91 |
| 3 months | 52.67±21.12 | 50.53±23.01 | 46.69±19.07 | 0.31 |
*Conclusions: As expected, individuals with CYP3A5 expressor genotypes (CYP3A5*1/*1 and *1/*3) were shown to require higher daily doses of tacrolimus and had lower tacrolimus trough concentrations than nonexpressors (CYP3A5*3/3) (Table 1). Despite this, CYP3A5 genotype did not influence renal function at any time point (Table 2). CYP3A5 genotype does not appear to be a risk factor for predicting the development of tacrolimus nephrotoxicity.
To cite this abstract in AMA style:
Kimpton JE, Hughes AJ, MacPhee I. CYP3A5 Genotype Had No Influence on Renal Function after Renal Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/cyp3a5-genotype-had-no-influence-on-renal-function-after-renal-transplantation/. Accessed February 27, 2021.« Back to 2019 American Transplant Congress