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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
JournalPflugers Archiv European Journal of Physiology
Volume473
Issue number4
Pages (from-to)595-610
ISSN0031-6768
DOIs
Publication statusPublished - Apr 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • Acute kidney injury
  • Chronic kidney disease
  • Entresto®
  • Ischemia–reperfusion
  • Kidney
  • Partial nephrectomy
  • Valsartan

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