Introduction: Non-adherence is an important risk factor for late rejection (rejection > 3 months post-transplant) and is the main reason why 17-29 year old kidney transplant recipients (KTRs) have the worst 5-year allograft survival rates compared with all other age categories. We investigated whether within-patient variability in Tacrolimus levels, a marker of non-adherence, predicts late rejection and graft loss in young adult KTRs.

Methods: Variability in Tacrolimus levels was calculated in young adult KTRs transplanted between January 2005 and May 2014 in a single center. The 5 most recent outpatient Tacrolimus levels > 6 months post-transplant (or the 5 most recent levels prior to the late rejection episode) were utilised for the analysis. Cox regression and ROC-curve analysis was used to evaluate the ability of variability in Tacrolimus levels to predict late rejection and graft-loss.

Results: Of 75 young adult KTRs (49m,26f;aged 17-29 yrs); 5 developed late rejection and 7 graft-loss (both 10-74 months post-transplant) during a median follow-up of 63 months. Patients with late rejection / graft loss had higher median variability in Tacrolimus levels compared to patients without late rejection (50% vs 20%, p = 0.02) / graft loss (50% vs 20%, p<0.001). Using the median of variability (21%) as a threshold, no late rejections were noted in the low variability group versus 5 in the high variability group (1 vs 6 for graft loss). In a Cox regression model adjusted for age at transplant, sex, living donor, previous transplant, pre-emptive transplant and total HLA mismatch, variability in Tacrolimus levels was the only variable significantly associated with late rejection (p=0.012) and graft loss (p=0.001) apart from age at transplant. Using a cut-off value of 21%, the AUC of the ROC-curve was 0.76 / 0.69 for predicting late rejection / graft loss.

Conclusion: Within-patient variability in Tacrolimus levels above 21% identifies young adult patients at increased risk of late rejection and graft loss. A potential strategy to improve adherence is a dedicated young adult service, previously shown to successfully reduce late rejection and graft loss.

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