Introduction Nonadherence to immunosuppressive medication can start any time after transplantation and is associated with rejection and graft loss. We have previously shown that high intrapatient variability (IPV) of tacrolimus levels 6-12mths post-transplant (PT) can be used as a surrogate marker for adherence and that a high IPV can predict early and late rejection and graft loss. In this study we compare IPV of tacrolimus levels 6-12mths PT with IPV 6mths preceding an episode of late first episode rejection (>18mths).

Method We retrospectively analysed 668 patients who received a low risk kidney transplant between Nov 05-Dec 14. Patients who developed rejection in the first 18mths PT or had less than 4 tacrolimus levels in the 6mths prior to rejection were excluded. All patients received alemtuzumab induction and tacrolimus monotherapy with a steroid sparing protocol and target tacrolimus level of 5-8ng/ml. Controls were chosen as patients transplanted within 1 month before and after each rejection case (N=59). Tacrolimus levels at matched time intervals to the rejection cases were used for analysis.

Results 39 cases of late rejection were identified. Mean time to rejection was 3.35±1.99 yrs.

There was no difference in IPV at 6-12mths PT and 6mths prior to rejection in those that developed late rejection (p=0.32). There was no difference in IPV at 6-12mths PT and 6mths prior to the matched time interval in those that did not develop late rejection (p=0.71)

Conclusion This study shows that patients who experience late rejection have significantly higher IPV at both 6-12mths post-transplant and 6 mths preceding the rejection episode compared to the IPV at similar time points of patients who do not develop late rejection. The study suggests that patients who have a high IPV at 6-12mths post-transplant may sustain this high IPV while those with a low IPV at 6-12mths may sustain a low IPV. Patients with a high IPV at 6-12mths post-transplant should be targeted for intervention to reduce IPV and prevent rejection. This analysis supports the use of IPV of tacrolimus levels as a tool to assess patients at risk of developing rejection throughout their transplant lifetime.

CITATION INFORMATION: Goodall D, Willicombe M, Swerdlow D, McLean A, Taube D. Early and Late High Intrapatient Variability of Tacrolimus Levels Can Predict Late Renal Allograft Rejection. Am J Transplant. 2017;17 (suppl 3).

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