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

Clin Nephrol. 2020 Nov;94(5):245-251. doi: 10.5414/CN110250.

Abstract

Background: There is conflicting data regarding the association of pre-transplant AT1R antibody levels and long-term outcomes following kidney transplantation.

Materials and methods: 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.

Results: 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 > 17 U/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 > 10 U/mL (HR 2.64, 95% Cl 1.35 - 5.17, p = 0.04) and AT1R antibodies > 17 U/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).

Conclusion: Our study indicates that in patients with a functioning kidney allograft > 5 years, pre-transplant AT1R antibodies may be associated with a greater risk of rejection and late graft failure.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Female
  • Graft Rejection / etiology*
  • HLA Antigens / immunology
  • Humans
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / mortality
  • Male
  • Middle Aged
  • Receptor, Angiotensin, Type 1 / immunology*
  • Time Factors
  • Transplantation, Homologous

Substances

  • Autoantibodies
  • HLA Antigens
  • Receptor, Angiotensin, Type 1