Background: De novo anti-HLA donor specific antibodies (dnDSA) are associated with poorer outcomes in kidney transplant recipients. Nonetheless, their monitoring post transplant is not widespread, in large part because the management of patients with dnDSA remains undetermined. We hypothesized that in this population, calcineurin inhibitor (CNI) levels would be an independent predictor of graft loss.

Methods: We analyzed a cohort of unsensitized patients for whom anti-HLA antibody screening was performed prospectively posttransplant. During the screening period between January 2005 and April 2016, 42 patients developed dnDSA. We used Cox modeling to measure the association between tacrolimus exposure (mean of levels at 1,3 ,6, 12 and 24mo post DSA detection) and graft loss. We progressively adjusted the model for independent predictors reported recently: DGF, nonadherence, tubulitis and transplant glomerulopathy. We conducted sensitivity analyses using all tacrolimus levels available between 1 and 24mo post DSA detection.

Results: There was no difference in the clinical characteristics nor in the histological scores of patients biopsied for clinical indication versus those biopsied solely because of positive dnDSA detection. Cox modeling revealed a strong relationship between mean tacrolimus levels following dnDSA detection and graft loss, with a hazard ratio of 0.49 (95% CI, 0.33–0.75) which persisted following adjustment for established independent predictors (HR, 0.52, 95% CI, 0.30–0.89). Kaplan Meier analysis by tertiles of tacrolimus levels and receiver operating curve analysis concurred to show that a threshold of 5.3 ng/ml could be predictive of graft survival (AUC 0.75; p=0.01; sens 80%, spec 67%).

Conclusion: These data are highly relevant, because they suggest that anti-HLA antibody monitoring and identification of dnDSA post transplant would be useful to optimize maintenance immunosuppression and improve graft outcomes.

CITATION INFORMATION: Béland M.-A, Noël R, Côté I, Lapointe I, Wagner E, Riopel J, Latulippe E, Désy O, Béland S, Houde I, De Serres S. Higher Tacrolimus Blood Levels Predict Better Graft Survival in Kidney Recipients with De Novo DSA. Am J Transplant. 2017;17 (suppl 3).

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