[Neprilysin inhibition and chronic kidney disease].

Abstract

Patients with chronic kidney disease (CKD) have a higher incidence of cardiovascular (acute and chronic) events, which in turn have an increased risk of progression to end-stage renal disease (ESRD) Inhibition of neprilysin, in addition to offering a new therapeutic target in patients with heart failure, could represent a potential improvement strategy in cardiovascular and renal outcome of patients with CKD. Inhibition of neprilysin by inhibiting the breakdown of natriuretic peptides, increases their bioavailability resulting in an increase in diuresis and sodium excretion and, in addition to exerting an inhibition of the renin-angiotensin-aldosterone (RAAS) system. Inhibition of RAAS, in turn, generates a series of counter-regulations that can balance the adverse effects present in CKD and heart failure (HF). The idea of blocking neprilysin is not very recent, but the first drugs used as inhibitors had an inadmissible incidence of angioedema. Among the latest generation molecules that can perform a specific inhibitory action on the neprilysin receptor and, at the same time, on the angiotensin II receptor thanks to the association with valsartan there is the LCZ696 (sacubitril / valsartan). This drug has shown promising benefits both in the treatment arterial hypertension and heart failure. It is hoped that equally positive effects may occur in CKD patients, particularly those with macroproteinuria.

• Authors: Luca Di Lullo, Claudio Ronco, Antonio Bellasi, Mario Cozzolino, Fulvio Floccari, Vincenzo Barbera, Simone Verdesca, Rodolfo Rivera, Antonio De Pascalis, Anna Mudoni, Antonio Santoro
• Journal: Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia (G Ital Nefrol) Vol. 34 Issue 5 Pg. 102-112 (Sep 28 2017) ISSN: 1724-5990 [Electronic] Italy
• Vernacular Title: Gli inibitori della Neprilisina nei pazienti affetti da Malattia Renale Cronica e Sindrome Cardio:Renale.
• PMID: 28963831 (Publication Type: Journal Article, Review)
• Copyright: Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Biphenyl Compounds
• Drug Combinations
• Natriuretic Peptides
• Tetrazoles
• Valsartan
• Neprilysin
• sacubitril and valsartan sodium hydrate drug combination

Topics

• Aminobutyrates (therapeutic use)
• Angioedema (chemically induced)
• Angiotensin Receptor Antagonists (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Biphenyl Compounds
• Cardiovascular Diseases (etiology, prevention & control)
• Clinical Trials as Topic
• Disease Progression
• Diuresis (drug effects)
• Drug Combinations
• Heart Failure (drug therapy)
• Humans
• Hypertension (drug therapy)
• Kidney Failure, Chronic (etiology, prevention & control)
• Models, Biological
• Molecular Targeted Therapy
• Natriuresis (drug effects)
• Natriuretic Peptides (metabolism)
• Neprilysin (antagonists & inhibitors)
• Proteinuria (drug therapy)
• Renal Insufficiency, Chronic (complications, drug therapy, metabolism)
• Renin-Angiotensin System (drug effects)
• Tetrazoles (therapeutic use)
• Valsartan