Angiotensin-converting enzyme 2 activity in patients with chronic kidney disease

Background. Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of the renin-angiotensin system that counteracts the adverse effects of angiotensin II. In heart failure patients, elevated plasma ACE2 activity predicted adverse events and greater myocardial dysfunction. We aimed to describe plasma ACE2 activity and its clinical associations in patients with kidney disease. Methods. Patients recruited from a single centre comprised of chronic kidney disease Stage III/IV (CKD), haemodialysis patients and kidney transplant recipients (KTRs). Plasma ACE2 enzyme activity was measured using a fluorescent substrate assay in plasma, collected at baseline and stored at -80°C. Linear regression was performed in both males and females separately to determine the covariates associated with log-transformed ACE2. Results. The median (interquartile range) plasma ACE2 activity in pmol/mL/min was 15.9 (8.4-26.1) in CKD (n = 59), 9.2 (3.9-18.2) in haemodialysis (n = 100) and 13.1 (5.7-21.9) in KTR (n = 80; P < 0.01). In male haemodialysis patients, ACE2 activity was 12.1 (6.8-19.6) compared with 4.4 (2.5- 10.3) in females (P < 0.01). Log-transformed ACE2 plasma activity was associated with post-haemodialysis systolic blood pressure in females [β-coefficient 0.04, 95% confidence interval (95% CI) 0.01-0.06, P = 0.006]. In males, log-transformed ACE2 plasma activity was associated with B-type natriuretic peptide (β-coefficient 0.39, 95% CI 0.19-0.60, P < 0.001). Plasma ACE2 activity was not associated with mortality. Conclusions. Plasma ACE2 activity is reduced in haemodialysis patients compared with CKD patients, and in female haemodialysis patients compared with male. The different associations of plasma ACE2 activity between male and female haemodialysis patients indicate that the role of ACE2 in cardiovascular disease may differ by gender.