ArticleCardiovascular diabetology2019
The combination of a neprilysin inhibitor (sacubitril) and angiotensin-II receptor blocker (valsartan) attenuates glomerular and tubular injury in the Zucker Obese rat.
Article in Cardiovascular diabetology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Optimizing diabetic kidney disease animal models: Insights from a meta-analytic approach.Animal models and experimental medicine · 2023Pooled it
- Association of angiotensin receptor-neprilysin inhibitor therapy with changes in eGFR slope and home blood pressure in patients with chronic kidney disease.Clinical and experimental nephrology · 2026Article
- Decoding cardiorenal crosstalk: Intercellular communication mechanisms and therapeutic insights in cardiorenal syndrome.iScience · 2026Review
- A State-of-the-Art Review Exploring the Cardiovascular Outcomes of Renin-Angiotensin Inhibitors in Acute Kidney Injury.Cardiorenal medicine · 2026Review
- Angiotensin receptor blocker ameliorates the development of tubulointerstitial injury and fibrosis associated with tubular proteinuria observed in subclinical diabetic kidney disease.Frontiers in pharmacology · 2026Article
- Class-Specific Effects of ARBs Versus ACE Inhibitors on Survival and Cardiovascular Outcomes in MASLD.International journal of molecular sciences · 2025Article
- Elucidating the function of clusterin in the progression of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- BOLD MRI to Evaluate the Effects of Sacubitril/Valsartan on Renal Protection in Type 2 Diabetics.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Sacubitril/Valsartan Combination Partially Improves Cardiac Systolic, but Not Diastolic, Function through β-AR Responsiveness in a Rat Model of Type 2 Diabetes.International journal of molecular sciences · 2024Article
- Role of angiotensin receptor-neprilysin inhibitor in diabetic complications.World journal of diabetes · 2024Review
- Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease.Diabetology & metabolic syndrome · 2024Article
- Impact of sacubitril/valsartan on cardiac and systemic hypoxia in chronic heart failure.iScience · 2024Article
- Potential renoprotective effects and possible underlying mechanisms of angiotensin receptor-neprilysin inhibitors in cardiorenal syndrome.Frontiers in medicine · 2024Review
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Updates for Cardio-Kidney Protective Effects by Angiotensin Receptor-Neprilysin Inhibitor: Requirement for Additional Evidence of Kidney Protection.Journal of the American Heart Association · 2023Review
- Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review.Frontiers in endocrinology · 2023Review
- Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions.JACC. Basic to translational science · 2023Review
- The history and mystery of sacubitril/valsartan: From clinical trial to the real world.Frontiers in cardiovascular medicine · 2023Review
- Article
- Potential Impacts of Hydralazine as a Novel Antioxidant on Cardiovascular and Renal Disease-Beyond Vasodilation and Blood Pressure Lowering.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveDiabetic nephropathy (DN) is characterized by glomerular and tubulointerstitial injury, proteinuria and remodeling. Here we examined whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses renal injury in a pre-clinical model of early DN more effectively than valsartan monotherapy.
methodsSixty-four male Zucker Obese rats (ZO) at 16 weeks of age were distributed into 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val) (68 mg kg
resultsMean arterial pressure (MAP) increased in ZOC (+ 28%), but not in ZOSV (- 4.2%), ZOV (- 3.9%) or ZOH (- 3.7%), during the 10 week-study period. ZOC were mildly hyperglycemic, hyperinsulinemic and hypercholesterolemic. ZOC exhibited proteinuria, hyperfiltration, elevated renal resistivity index (RRI), glomerular mesangial expansion and podocyte foot process flattening and effacement, reduced nephrin and podocin expression, tubulointerstitial and periarterial fibrosis, increased NOX2, NOX4 and AT
conclusionsCompared to val monotherapy, sac/val was more effective in reducing proteinuria, renal ultrastructure and tubular injury in a clinically relevant animal model of early DN. More importantly, these renoprotective effects were independent of improvements in blood pressure, glycemia and nitroso-oxidative stress. These novel findings warrant future clinical investigations designed to test whether sac/val may offer renoprotection in the setting of DN.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.