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A Retrospective Observational Analysis of Tacrolimus Metabolism Rate: No Evidence for Impact on Renal Function

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

Renal Medicine and Transplantation, St George’s University Hospitals NHS Foundation Trust, London, United Kingdom

Meeting: 2019 American Transplant Congress

Abstract number: A252

Keywords: FK506, Immunosuppression, Kidney transplantation, Nephrotoxicity

Session Information

Session Name: Poster Session A: Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: A previous publication found that fast metabolisers of tacrolimus had inferior renal function compared to slow metabolisers in a Caucasian population (Thölking et al., 2014); the purpose of this study was to assess if this could be replicated in an ethnically diverse renal transplant population.

*Methods: We performed a retrospective observational analysis of 295 participants from previous genotyping studies who underwent renal transplantation between 1995 and 2017. Patients were assigned a tacrolimus metabolism rate as defined by the mean of their trough blood tacrolimus concentrations normalised by their tacrolimus doses (C/D ratios) at day 7, day 14 and 3 months post-transplantation. Participants were stratified into slow, intermediate or fast metaboliser groups (mean C/D ratio of ≥1.55, 1.05-1.54 or <1.05 respectively). Glomerular filtration rate was estimated using the CKD-EPI equation (eGFR). Groups were compared by the Kruskal-Wallis H test.

*Results:

Table 1. Participant numbers by ethnicity and metaboliser group.

Fast Metabolisers Intermediate Metabolisers Slow Metabolisers
Black 38 3 3
Caucasian 74 63 57
South Asian 17 12 16
Other 6 3 3

Table 2. Mean eGFR (ml/min/1.73m2) by metaboliser group at day 7, day 14 and 3 months after renal transplantation.

Time Fast Metabolisers (n=135) Intermediate Metabolisers (n=81) Slow Metabolisers (n=79) P value
Day 7 28.27±26.57 32.79±22.91 32.03±26.01 0.12
Day 14 33.73±25.94 39.42±22.68 38.94±26.81 0.07
3 months 46.46±21.40 49.44±17.57 50.24±21.52 0.23

*Conclusions: Tacrolimus metabolism rate did not influence renal function after renal transplantation at any time point (Table 2). This is in contrast to previously published data which came from a Caucasian population. Given the ethic heterogeneity in our population (Table 1), we analysed our Caucasian data separately (n=194) but remained unable to demonstrate an impact. These data do not support tacrolimus metabolism rate, defined as mean C/D ratio, as a suitable risk factor for predicting tacrolimus nephrotoxicity.

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To cite this abstract in AMA style:

Hughes AJ, Kimpton JE, MacPhee I. A Retrospective Observational Analysis of Tacrolimus Metabolism Rate: No Evidence for Impact on Renal Function [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/a-retrospective-observational-analysis-of-tacrolimus-metabolism-rate-no-evidence-for-impact-on-renal-function/. Accessed May 17, 2025.

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