Abstract: FR-PO757
Protective Effect of AT1R Antibodies in Patients With ESKD on Hemodialysis
Session Information
- Hypertension and CVD: Clinical, Outcomes, Trials
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1502 Hypertension and CVD: Clinical‚ Outcomes‚ and Trials
Authors
- Gonzalez Suarez, Maria Lourdes, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Fedarko, Neal S., Johns Hopkins University, Baltimore, Maryland, United States
- Hwang, Seungyoung, Boston Strategic Partners Inc, Boston, Massachusetts, United States
- Tin, Adrienne, The University of Mississippi Medical Center, Jackson, Mississippi, United States
- Shafi, Tariq, The University of Mississippi Medical Center, Jackson, Mississippi, United States
Background
The renin-angiotensin system (RAS) is one of the major contributors to accelerated CVD. Angiotensin II binds to its type 1 receptor (AT1R) contributing to the clinical phenotype characterized by hypertension, and CVD outcomes. Autoantibodies to AT1R (AT1RAb) mimic angiotensin II effects by binding to its receptor active site. AT1RAb have been described in severe preeclampsia, malignant hypertension, and kidney allograft failure. We assessed the association of AT1RAb with mortality in patients with ESKD on hemodialysis (HD).
Methods
Using serum samples from a national prospective cohort study of ESKD patients on HD, we measured AT1RAb by quantitative ELISA using two methods: a) a novel purified antigen sequence AFHYESQ (active site) assay; b) a commercial full length AT1R assay. We assessed the association of AT1RAb with mortality using Cox models adjusting for demographic and clinical factors.
Results
A total of 443 samples were measured by both ELISAs. Mean age was 61 (SD±13.9), 45% were women and 39% were Black. Charlson score was 5.7±1.9. Mean number of years on dialysis was 6 (SD±4.3). 211 patients died during follow-up. Compared to the lowest tertile of AT1RAb, the highest tertile was associated with a 42% lower risk of death using the novel assay (HR 0.58; 95% CI, 0.41-0.82; p=0.002). Comparison of both assays is presented in the Table 1.
Conclusion
Our findings of a protective effect by AT1RAb that activate AT1 receptor are intriguing. The use of angiotensin receptor blockers, which can elevate circulating levels of AT1RAb may be a possible explanation. Larger population studies are needed to determine ARBs association with AT1RAb.
Association of AT1R Levels with All-Cause Mortality
| Events/N (IR per 1000 PY) | Model 1 Unadjusted 211/443 (27.0) HR (95% CI) | . p | Model 2 Adjusted* 202/433 (26.0) HR (95%CI) | . p |
| Novel Assay (AFHYESQ), ug/ml Tertile 1, lowest Tertile 2 Tertile 3, highest | . Reference 0.93 (0.68-1.28) 0.64 (0.45-0.90) | . — 0.665 0.01 | . Reference 0.98 (0.71-1.35) 0.58 (0.41-0.82) | . — 0.905 0.002 |
| Commercial assay, ug/ml Tertile 1, lowest Tertile 2 Tertile 3, highest | . Reference 0.99 (0.71-1.37) 0.64 (0.45-0.89) | . — 0.951 0.009 | . Reference 1.00 (0.72-1.39) 0.69 (0.49-0.97) | . — 0.986 0.03 |
*Adjusted for age, sex, race, Charlson score, diabetes, albumin, hemoglobin, phosphorus, PTH and spKtv
Funding
- Other NIH Support