Pre-transplant AT1R antibodies and long-term outcomes in kidney transplant recipients with a functioning graft for more than 5 years.

Abstract

There is conflicting data regarding the association of pre-transplant AT1R antibody levels and long-term outcomes following kidney transplantation. We examined the association between pre-transplant antibodies and long-term graft outcome by assaying pre-transplant sera from 125 kidney transplant recipients from 1999 to 2009. The mean age at transplant was 55.7±13 years; 67.2% were male, 87.2% were Caucasian, and 67.2% received a deceased donor transplant. Induction therapy included 44.8% thymoglobulin. Human leukocyte antigen (HLA) donor-specific antibodies (DSA) were present in 22 (17.6%) patients, while AT1R antibodies >17U/mL were present in 24 (19.2%). The mean AT1R antibodies level was 13±7.2 U/mL. Patients were followed-up for 7.1±1.9 years after transplant. Pre-transplant AT1R antibodies were associated with rejection (p<0.0001), antibody-mediated rejection (ABMR) (p<0.0001), and death-censored graft failure (DCGF) (p=0.01). This was confirmed by univariate Cox regression analyses for AT1R antibodies >10U/mL (HR 2.64, 95% Cl 1.35 - 5.17, p=0.04) and AT1R antibodies >17U/mL (HR=1.74, 95% Cl 1.061-2.98, p=0.04). Multivariable analyses did not retain AT1R antibodies as independent predictors of DCGF; however, pre-transplant HLA, DSA, and acute rejection during the first year were associated with DCGF (HR 2.07, 95% Cl 1.13 - 3.78, p=0.02 and HR 3.03, 95% Cl 1.13 - 3.78, p=0.0002, respectively). Our study indicates that in patients with a functioning kidney allograft >5years, pre-transplant AT1R antibodies may be associated with a greater risk of rejection and late graft failure.