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CYP3A5 Genotype Had No Influence on Renal Function after Renal Transplantation

J. E. Kimpton, A. J. Hughes, I. MacPhee

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

Related Abstracts
  • Tacrolimus Dose Requirement Based on the CYP3A5 Genotype in Renal Transplant Patients.
  • A Randomized-Controlled Trial Comparing the Efficacy of CYP3A5 Genotype-Based with Bodyweight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation.

*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.

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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.

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