Gli inibitori della Neprilisina nei pazienti affetti da Malattia Renale Cronica e Sindrome Cardio-Renale

I pazienti affetti da malattia renale cronica (CKD) presentano una maggiore incidenza di eventi cardiovascolari (acuti e cronici) che, a loro volta, comportano un rischio aumentato di progressione verso la malattia renale cronica terminale (end – stage renal disease – ESRD) L’inibizione della neprilisina, oltre ad offrire un nuovo target terapeutico nei pazienti affetti da scompenso cardiaco, potrebbero rappresentare una strategia di potenziale miglioramento negli outcomes, sia cardio-vascolari che renali, dei pazienti affetti da CKD. L’inibizione della neprilisina, favorendo una maggiore biodisponibilità dei peptidi natriuretici atriali, determina un incremento della diuresi e della natriuresi, oltre ad esercitare un’azione di inibizione del sistema renina – angiotensina – aldosterone (RAAS). L’inibizione del RAAS, a sua volta, genera una serie di controregolazioni in grado di bilanciarne gli effetti sfavorevoli in corso di CKD e di insufficienza cardiaca (HF). L’idea del blocco della neprilisina non è recentissima, ma i primi farmaci impiegati, essendo molecole di associazione con antagonisti dell’angiotensina II (ARBs), risultavano gravati da un’incidenza inammissibile di angioedema. Tra le molecole di ultima generazione in grado di esercitare un’azione inibente specifica sul recettore della neprilisina e su quello dell’angiotensina II, grazie alla associazione con il valsartan, vi è l’LCZ696 (sacubitril/valsartan) che ha mostrato evidenti benefici sia nel trattamento dell’ipertensione arteriosa che nell’insufficienza cardiaca. PAROLE CHIAVE: Neprilisina, peptidi natriuretici, sacubitril/valsartan, ipertensione arteriosa, scompenso cardiaco, CKD 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 LCZ696Patients 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.