Circulating angiotensin converting enzyme 2 activity as a biomarker of silent atherosclerosis in patients with chronic kidney disease.
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.



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.



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.



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.
Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
Lidia
L
Anguiano
Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
Marta
M
Riera
Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
Julio
J
Pascual
Nephrology Research Laboratory, Institute for Biomedical Research, IRB, Lleida, Spain.
José Manuel
JM
Valdivielso
Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
Clara
C
Barrios
Nephrology Research Laboratory, Institute for Biomedical Research, IRB, Lleida, Spain; Department of Nephrology and UDETMA, University Hospital Arnau de Vilanova, Lleida, Spain.
Angels
A
Betriu
Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
Sergi
S
Clotet
Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
Sergi
S
Mojal
Nephrology Research Laboratory, Institute for Biomedical Research, IRB, Lleida, Spain; Department of Nephrology and UDETMA, University Hospital Arnau de Vilanova, Lleida, Spain.
Elvira
E
Fernández
Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain. Electronic address: 92844@parcdesalutmar.cat.
María José
MJ
Soler
D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D055109:Ankle Brachial Index; D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002339:Carotid Arteries / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D048909:Diabetes Complications / Q000097:blood; D005260:Female; D005263:Femoral Artery / Q000473:pathology; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality; D012307:Risk Factors; D012680:Sensitivity and Specificity
D015415:Biomarkers; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
Cardiovascular disease; Chronic kidney disease; Circulating ACE2; Subclinical atherosclerosis