Abstract: SA-PO643

Intrapatient Tacrolimus Variability Has Similar Outcomes on Kidney Allograft Function between UK Transplant Centers

Session Information

Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

  • 1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics

Author

  • Ghita, Ryan, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom

Group or Team Name

  • UK Transplant Audit Collaborative
Background

Tacrolimus based immunosuppression regimes are the mainstay of treatment for transplant patients in the United Kingdom. High intrapatient variability (IPV) of tacrolimus levels has been associated with poorer kidney allograft function. A retrospective study looked at the effects of high IPV on eGFR in five transplant centers across the UK (Glasgow, Oxford, King’s London, Liverpool, Manchester).

Methods

Data was collected from patients who received a kidney transplant between 2009 and 2014 in one of the 5 UK centers. Tacrolimus trough levels were recorded at two time points - 6-12 months post transplant (T1) and most recent 12 months (T2). Exclusion criteria included patients that received dual-organ transplants or if death or graft loss occurred within two years of transplantation, or if their immunosuppression regimens included modified release tacrolimus.

For each transplant center, patients that fell into the highest and lowest IPV quartiles were identified and their MDRD eGFR were compared using a Mann-Whitney U-test. The results are in table1.

Results

Three of the comparisons between the high and low variability groups had a U-value lower than the critical value suggesting a significant difference in MDRD eGFR. In all other groups the median eGFR was lower in the high IPV group however this was not found to be statistically significant.

Conclusion

The results suggest a correlation between high IPV and worse allograft function, as determined by eGFR, throughout the UK transplant centers. However the small patient cohort in each center limits analysis. Further analysis will be performed merging the data from all centers which to the best of our knowledge will be the largest study looking at IPV with over 1000 patients.

Table 1: eGFR comparison between patients with high and low tacrolimus variability in UK Transplant Centers
 Glasgow (n=168)Oxford (n=284)Liverpool (n=171)Manchester (n=313)King's London (n=134)
T1
MEDIAN (IQR) eGFR of low IPV patients
62
(49-77)
54
(45-64)
51.5
(38-57.3)
49
(38.5-61)
56
(48.3-73.3)
T1
MEDIAN (IQR) eGFR of high IPV patients
46
(34.3-58.6)
50
(35.5-58)
44
(36-52)
48.5
(39.3-59.3)
55
(43-67)
P – value0.0010.020.190.590.52
T2
MEDIAN (IQR) eGFR of low IPV patients
55
(47-73)
52
(39-65)
50
(36-56)
48
(38-56.5)
58.5
(48-73.8)
T2
MEDIAN (IQR) eGFR of high IPV patients
53.5
(28-64.8)
47
(37.5-64)
46
(33.5-58)
44
(30-60.6)
51
(28.8-63.8)
P – value0.130.260.470.690.03