Introduction. Chronic active antibody mediated rejection (caABMR) is one of the major causes of long-term kidney graft loss. It is hypothesized that frequent underexposure and suboptimal trough levels of immunosuppressive drugs, in particular CNI, are risk factors for the development of caABMR. Previously, it was found that high intra-patient variability in tacrolimus exposure is associated with poor long-term outcome in kidney transplantation and may serve as a substitute parameter for frequent underexposure and/or non-adherence. In this study we investigated the association between tacrolimus exposure and the development of caABMR.

Methods. To investigate the possible association between tacrolimus exposure and the development of caABMR, we retrospectively included 58 biopsy proven caABMR patients and compared them to 192 matched controls. Control cases were matched for age, year of transplantation and type of kidney donor. All patients were on a standard regimen of tacrolimus and MMF. The intra-patient variability (IPV) was calculated from pre-dose tacrolimus concentrations measured in the 3 years prior to caABMR diagnosis. The tacrolimus IPV for the matched controls was measured over a similar period of time dependent on the case's time to caABMR diagnosis. Besides IPV also mean trough tacrolimus levels and duration of tacrolimus underexposure were compared between both groups.

Results. The median time after transplantation to caABMR diagnosis was 6 years [range 2-14 years]. The tacrolimus IPV was relatively high in both groups with 24.0% [range 9.1%-48.3%] for the caABMR patients versus 23.6% [range 3.3%-45.8%] for the controls (p=0.68). However, the mean tacrolimus trough levels showed a small but statistically significant difference with a tacrolimus concentration of 5.8 ng/mL for the caABMR patients and 6.3 ng/mL for the controls (P=0.03).

Conclusion. A lower mean exposure to tacrolimus but not a high intra-patient variability is associated with the development of caABMR.

CITATION INFORMATION: Sablik K, Clahsen–van Groningen M, Van Gelder T, Betjes M. A Lower Mean Exposure to Tacrolimus, Not Intra-Patient Variability Is Associated with Chronic Active Antibody Mediated Rejection. Am J Transplant. 2017;17 (suppl 3).

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