Protective effect of sacubitril/valsartan (Entresto®) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy

Juan Brignone*, Mia Jensen, Boye L. Jensen, Kasper Bostlund Assersen, Jens P. Goetze, Lars Jødal, Trine Borup Andersen, Sigriður Olga Magnusdottir, Brian Kloster, Morten Jønler, Lars Lund

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)


Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n = 8), PN + vehicle (n = 8), sham + Entresto (49/51 mg/day; n = 4) and sham + vehicle (n = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 ± 6 mL/min, left 31 ± 7 mL/min) accounted for the total GFR (56 ± 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 ± 6 mL/min, P < .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.

Original languageEnglish
Article numbergfac200
JournalNephrology, Dialysis, Transplantation
Issue number1
Pages (from-to)80-92
Number of pages13
Publication statusPublished - Jan 2023

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.


  • Aminobutyrates
  • Animals
  • Biphenyl Compounds
  • Drug Combinations
  • Glomerular Filtration Rate
  • Kidney
  • Nephrectomy
  • Swine
  • Tetrazoles
  • Valsartan
  • partial nephrectomy
  • albuminuria
  • natriuretic peptides
  • GFR
  • acute kidney injury


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