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Am J Transplant. 2013 Oct;13(10):2567-76. doi: 10.1111/ajt.12397. Epub 2013 Aug 6.

Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss.

Author information

1
Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France; LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France; Nantes University, Centre d'Investigation Clinique biothérapie, Nantes, France.

Abstract

The angiotensin II type 1 receptor (AT1R) is an emerging target of functional non-HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT1R as a risk factor for graft survival and acute rejection (AR). The study included 599 kidney recipients between 1998 and 2007. Serum samples were analyzed in a blinded fashion for anti-AT1R antibodies (AT1R-Abs) using a quantitative solid-phase assay. A threshold of AT1R-Ab levels was statistically determined at 10 U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT1R-Abs >10 U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT1R-Abs >10 U had a 2.6-fold higher risk of graft failure from 3 years posttransplantation onwards (p = 0.0005) and a 1.9-fold higher risk of experiencing an AR episode within the first 4 months of transplantation (p = 0.0393). Antibody-mediated rejection (AMR) accounted for 1/3 of AR, whereby 71.4% of them were associated with >10 U of pretransplant AT1R-Abs. Pretransplant anti-AT1R-Abs are an independent risk factor for long-term graft loss in association with a higher risk of early AR episodes.

KEYWORDS:

Acute allograft rejection; allosensitization; angiotensin II receptors; antibody mediated rejection; pretransplant; survival

PMID:
23919486
DOI:
10.1111/ajt.12397
[Indexed for MEDLINE]
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