Original Article
Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss

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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.

Key words:

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

Abbreviations

ACMR
acute cellular mediated rejection
AMR
antibody-mediated rejection
AR
acute rejection
ATG
antithymocyte-globulin
AT1R
angiotensin type 1 receptor
AT1R-Abs
anti-AT1R antibodies
CDC
complement dependent cytotoxicity
CHO
Chinese Hamster Ovary
DGF
delayed graft function
DSA
donor specific antibodies
eGFR
estimated glomerular filtration rate
ELISA
enzyme-linked immunosorbent assay
HLA
human leukocyte antigen
HR
hazard ratio
IF
indirect immunofluorescence
IL2
interleukin 2
LCT
micro-lymphocytotoxicity
MHC
major-histocompatibility-complex (MHC)
MICA
MHC class I-related molecules A
MMF
mycophenolate mofetil
PRA
panel reactive antibodies.

Cited by (0)

Both authors contributed equally.