Protection of kidney function and tissue integrity by pharmacologic use of natriuretic peptides and neprilysin inhibitors

Juan Brignone*, Kasper Bostlund Assersen, Mia Jensen, Boye L. Jensen, Brian Kloster, Morten Jønler, Lars Lund

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

With variable potencies atrial-, brain-type and c-type natriuretic peptides (NP)s, best documented for ANP and its analogues, promote sodium and water excretion, renal blood flow, lipolysis, lower blood pressure, and suppress renin and aldosterone secretion through interaction predominantly with cGMP-coupled NPR-A receptor. Infusion of especially ANP and its analogues up to 50 ng/kg/min in patients with high risk of acute kidney injury (cardiac vascular bypass surgery, intraabdominal surgery, direct kidney surgery) protects kidney function (GFR, plasma flow, medullary flow, albuminuria, renal replacement therapy, tissue injury) at short term and also long term and likely additively with the diuretic furosemide. This documents a pharmacologic potential for the pathway. Neprilysin (NEP, neutral endopeptidase) degrades NPs, in particular ANP, and angiotensin II. The drug LCZ696, a mixture of the neprilysin inhibitor sacubitril and the ANGII-AT1 receptor blocker valsartan, was FDA approved in 2015 and marketed as Entresto®. In preclinical studies of kidney injury, LCZ696 and NPs lowered plasma creatinine, countered hypoxia and oxidative stress, suppressed proinflammatory cytokines, and inhibited fibrosis. Few randomized clinical studies exist and were designed with primary cardiac outcomes. The studies showed that LCZ696/entresto stabilized and improved glomerular filtration rate in patients with chronic kidney disease. LCZ696 is safe to use concerning kidney function and stabilizes or increases GFR. In perspective, combined AT1 and neprilysin inhibition is a promising approach for long-term renal protection in addition to AT1 receptor blockers in acute kidney injury and chronic kidney disease.

OriginalsprogEngelsk
TidsskriftPflugers Archiv European Journal of Physiology
Vol/bind473
Udgave nummer4
Sider (fra-til)595-610
ISSN0031-6768
DOI
StatusUdgivet - apr. 2021

Bibliografisk note

Funding Information:
Authors were supported by the Region of Southern Denmark/Region Sjælland; Karen Elise Jensen Foundation; Novo Nordisk Foundation, The Danish National Research Foundation. Conflicts of interest: at time of submission of the manuscript, the authors declare that there are noconflicts of interest related to the project.

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