Lidia Anguiano1, Marta Riera1, Julio Pascual1, José Manuel Valdivielso2, Clara Barrios1, Angels Betriu3, Sergi Clotet1, Sergi Mojal4, Elvira Fernández3, María José Soler5. 1. Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain. 2. Nephrology Research Laboratory, Institute for Biomedical Research, IRB, Lleida, Spain. 3. Nephrology Research Laboratory, Institute for Biomedical Research, IRB, Lleida, Spain; Department of Nephrology and UDETMA, University Hospital Arnau de Vilanova, Lleida, Spain. 4. Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain. 5. Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain. Electronic address: 92844@parcdesalutmar.cat.
Abstract
BACKGROUND AND AIMS: Circulating Angiotensin Converting Enzyme 2 (ACE2) activity in chronic kidney disease (CKD) patients without previous history of cardiovascular disease (CVD) has been associated with classical risk factors (older age, diabetes and male gender). Furthermore, silent atherosclerosis has been described as a pathological link between CKD and CVD. We analyzed baseline ACE2 activity in non-dialysis CKD stages 3-5 (CKD3-5) patients as a biomarker of renal progression, silent atherosclerosis and CV events after 2 years of follow-up. METHODS: Prospective study of 1458 CKD3-5 subjects without any previous CV event included in the Spanish multicenter NEFRONA study. Association between baseline circulating ACE2 activity and renal parameters, carotid/femoral echography, atheromatous disease, ankle-brachial index, intima-media thickness, need of renal replacement therapy, cardiovascular events and mortality at 24 months of follow-up were analyzed. RESULTS: Patients with an increase in the number of territories with plaques at 24 months showed significantly higher levels of baseline ACE2 activity as compared to stable patients (29.6 (20.6-47.6)RFU/μL/h versus 35.7 (24.5-56), p < 0.001). Multivariate linear regression analysis showed that male gender, pathological ankle-brachial index and progressive silent atherosclerosis defined as an increased number of territories with plaques at 24 months were associated with increased baseline ACE2 activity. Male gender, older age, diabetes, smoking and increased baseline circulating ACE2 were independent predictors of atherosclerosis at 24 months of follow-up. CONCLUSIONS: In CKD3-5 patients, higher circulating ACE2 activity at baseline is associated with higher risk for silent atherosclerosis, suggesting that ACE2 may serve as a biomarker to predict CV risk before CVD is established.
BACKGROUND AND AIMS: Circulating Angiotensin Converting Enzyme 2 (ACE2) activity in chronic kidney disease (CKD) patients without previous history of cardiovascular disease (CVD) has been associated with classical risk factors (older age, diabetes and male gender). Furthermore, silent atherosclerosis has been described as a pathological link between CKD and CVD. We analyzed baseline ACE2 activity in non-dialysis CKD stages 3-5 (CKD3-5) patients as a biomarker of renal progression, silent atherosclerosis and CV events after 2 years of follow-up. METHODS: Prospective study of 1458 CKD3-5 subjects without any previous CV event included in the Spanish multicenter NEFRONA study. Association between baseline circulating ACE2 activity and renal parameters, carotid/femoral echography, atheromatous disease, ankle-brachial index, intima-media thickness, need of renal replacement therapy, cardiovascular events and mortality at 24 months of follow-up were analyzed. RESULTS:Patients with an increase in the number of territories with plaques at 24 months showed significantly higher levels of baseline ACE2 activity as compared to stable patients (29.6 (20.6-47.6)RFU/μL/h versus 35.7 (24.5-56), p < 0.001). Multivariate linear regression analysis showed that male gender, pathological ankle-brachial index and progressive silent atherosclerosis defined as an increased number of territories with plaques at 24 months were associated with increased baseline ACE2 activity. Male gender, older age, diabetes, smoking and increased baseline circulating ACE2 were independent predictors of atherosclerosis at 24 months of follow-up. CONCLUSIONS: In CKD3-5 patients, higher circulating ACE2 activity at baseline is associated with higher risk for silent atherosclerosis, suggesting that ACE2 may serve as a biomarker to predict CV risk before CVD is established.
Authors: María José Soler; Marta Riera; Heleia Roca-Ho; Vanesa Palau; Javier Gimeno; Julio Pascual Journal: Lab Invest Date: 2020-05-29 Impact factor: 5.662