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Kidney Week

Abstract: TH-PO467

The Role of Neprilysin in CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • Emrich, Insa E., None, Haschbach, RP, Germany
  • Vodovar, Nicolas, Inserm UMR-S 942, Paris, France
  • Untersteller, Kathrin, None, Haschbach, RP, Germany
  • Nougué, Hélène, Inserm UMR-S 942, Paris, France
  • Seiler, Sarah, Saarland University Hospital, Homburg, Germany
  • Fliser, Danilo, Saarland University Medical Centre, Homburg/Saar, Germany
  • Mebazaa, Alexandre, Inserm UMR-S 942, Paris, France
  • Launay, Jean-Marie, Inserm UMR-S 942, Paris, France
  • Heine, Gunnar H., Saarland University Faculty of Medicine, Homburg, Germany
Background

Since the introduction of sacubitril in clinical cardiology, neprilysin has become a major treatment target for patients suffering from heart failure. Neprilysin inhibition with sacubitril prolongs survival of patients with systolic heart failure, and elevated plasma neprilysin concentrations predict adverse cardiac outcome in non-nephrological cohorts. However, natriuretic peptides were recently shown to inhibit plasma neprilysin. As natriuretic peptides accumulate in chronic kidney disease (CKD), we hypothesized that high plasma neprilysin loses its predictive role in patients with impaired renal function.

Methods

We measured plasma levels of neprilysin concentration, neprilysin activity and brain natriuretic peptide (BNP) in 542 CKD G2 - G4 patients within the CARE FOR HOMe study. Patients were followed annually for predefined endpoints (a) hospitalization for acute decompensated heart failure, and (b) atherosclerotic cardiovascular events.

Results

During 5.1 ± 2.1 years, 63 hospitalizations for acute decompensated heart failure and 125 incident atherosclerotic cardiovascular events occurred.
Plasma BNP was inversely correlated with neprilysin activity (before adjustment for glomerular filtration rate: r = -0.118; p = 0.006; after adjustment: r = -0.193; p < 0.001), but not with neprilysin concentration (r = -0.022; p = 0.603 and r = 0.065; p = 0.132, respectively).
Both in univariate Kaplan-Meier and in multivariate Cox regression analyses, high plasma BNP and low, rather than elevated, neprilysin activity predicted future hospitalization for acute decompensated heart failure, whereas neprilysin concentration was not predictive. Further, BNP was an independent predictor of incident atherosclerotic cardiovascular events, while neprilysin concentration and activity were not.

Conclusion

In line with experimental studies, high natriuretic peptides may inhibit neprilysin activity in CKD. In accordance, high neprilysin activity and concentrations are no predictors of adverse cardiovascular outcome in CKD patients. Thus, neprilysin inhibitors should be implemented with caution in patients with advanced CKD, and further studies are needed to better understand the benefits and risks of neprilysin inhibitors in these patients.