Abstract
Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients.Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events).Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = −2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 (p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events (p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37–4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33–5.56) after adjustment for multiple variables.Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events.
Highlights
Cardiovascular (CV) disease is a major cause of death in patients undergoing hemodialysis (HD) treatment, and an extremely high rate of CV complications has been reported in these patients [1, 2]
The neprilysin is anticipated to be a promising biotarget for the reduction of CV risk in patients with chronic kidney disease (CKD) and cross-sectional study showed the usefulness of neprilysin for heart failure diagnosis in dialysis patients [14,15,16,17,18]
Almost studies exploring the neprilysin in patients with CKD enrolled the patients who were not receiving dialysis, and no evidence exists on circulating neprilysin as a pathologic surrogate to predict the incident CV events in patients undergoing HD treatment
Summary
Cardiovascular (CV) disease is a major cause of death in patients undergoing hemodialysis (HD) treatment, and an extremely high rate of CV complications has been reported in these patients [1, 2]. Natriuretic peptides have been introduced into the dialysis setting, based on their pathophysiologic role in heart failure, to assess for myocardial ischemia, systolic dysfunction, and risk of future cardiac events [7, 8]. The neprilysin is anticipated to be a promising biotarget for the reduction of CV risk in patients with chronic kidney disease (CKD) and cross-sectional study showed the usefulness of neprilysin for heart failure diagnosis in dialysis patients [14,15,16,17,18]. Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. The role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients
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