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5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
[Neprilysin inhibition and chronic kidney disease]
Luca Di Lullo1, Claudio Ronco2, Antonio Bellasi3
1UOC Nefrologia e Dialisi, Ospedale "L. Parodi"Delfino:, Colleferro, Roma, Italy.
Insights
Neprilysin inhibition, using sacubitril/valsartan, may improve cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. This approach enhances natriuretic peptides and inhibits the RAAS, potentially benefiting those with heart failure and proteinuria.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Patients with chronic kidney disease (CKD) face increased cardiovascular events and risk of end-stage renal disease (ESRD).
- Cardiovascular and renal complications are significant concerns in CKD patients.
Purpose of the Study:
- To explore neprilysin inhibition as a strategy to improve cardiovascular and renal outcomes in CKD.
- To evaluate the potential benefits of sacubitril/valsartan (LCZ696) in CKD patients, especially those with macroproteinuria.
Main Methods:
- Inhibition of neprilysin increases natriuretic peptide bioavailability, promoting diuresis and natriuresis.
- Simultaneous inhibition of the renin-angiotensin-aldosterone system (RAAS) may counteract adverse effects in CKD and heart failure (HF).
- Investigating novel dual neprilysin and angiotensin II receptor blockers like sacubitril/valsartan.
Main Results:
- Sacubitril/valsartan has demonstrated benefits in arterial hypertension and heart failure.
- Previous neprilysin inhibitors were associated with angioedema, limiting their use.
- LCZ696 combines neprilysin inhibition with angiotensin II receptor blockade.
Conclusions:
- Neprilysin inhibition presents a potential therapeutic avenue for improving cardiovascular and renal outcomes in CKD.
- Sacubitril/valsartan shows promise for CKD patients, particularly those with significant proteinuria.
- Further research is warranted to confirm the efficacy and safety of neprilysin inhibition in CKD management.
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.
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