title: Higher calcineurin inhibitor levels predict better kidney graft survival in patients with de novo donor-specific anti-HLA antibodies: a cohort study.
abstract: The development of de novo anti-HLA donor-specific antibodies (dnDSA) is associated with poorer outcomes in kidney transplant recipients. Despite this, antibody screening post-transplant is not widespread, largely because the optimal management of patients with dnDSA remains undetermined. We hypothesized that in this population, calcineurin inhibitor blood levels would be an independent predictor of graft loss. We analyzed a cohort of unsensitized patients for whom anti-HLA antibody screening was performed prospectively post-transplant. During the screening period between January 2005 and April 2016, 42 patients developed dnDSA. There was no difference in the clinical characteristics or the histological scores of patients biopsied for clinical indication versus those biopsied solely due to detection of dnDSA. 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 loss. These data suggest that anti-HLA antibody monitoring post-transplant could guide maintenance immunosuppression and improve graft outcomes.
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Béland
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lapointe
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Réal
authors.initials: R
authors.lastname: Noël
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Côté
authors.affiliation: Immunology and Histocompatibility Laboratory, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Wagner
authors.affiliation: Department of Pathology, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Riopel
authors.affiliation: Department of Pathology, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Latulippe
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Olivier
authors.initials: O
authors.lastname: Désy
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Béland
authors.affiliation: Department of Nephrology & Renal Transplantation, UCL Centre for Nephrology, Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Ciara N
authors.initials: CN
authors.lastname: Magee
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Houde
authors.affiliation: Transplantation Unit, Renal Division, Department of Medicine, Faculty of Medicine, University Health Center of Quebec, Laval University, Quebec, QC, Canada.
authors.forename: Sacha A
authors.identifier: http://orcid.org/0000-0002-7862-4935
authors.initials: SA
authors.lastname: De Serres
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood*
chemical_list: D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D016559:Tacrolimus
keywords: HLA-antibody post-transplantation; calcineurins antagonists; histocompatibility; immunogenetics; immunosuppression clinical; immunosuppression kidney clinical