Abstract 15879: LCZ696, an Angiotensin-receptor Neprilysin Inhibitor, Attenuates Cardiac Hypertrophy and Fibrosis in a Rat Model of Chronic Kidney Disease
Introduction: Chronic kidney disease (CKD) is associated with significant cardiovascular disease including uremic cardiomyopathy. LCZ696 (sacubitril/valsartan), is a promising new agent which has shown significant potential in treatment of chronic heart failure with reduced ejection fraction. We evaluated the effects of LCZ696 on cardiac tissue in a rat model of CKD.
Methods: Male Sprague Dawley rats underwent sham surgery or 5/6 nephrectomy and after two weeks the CKD animals were randomized to no treatment (CKD), valsartan (30 mg/kg) (VAL), or LCZ696 (60 mg/kg) (LCZ) by gavage. After 8 weeks of treatment, serum creatinine, tail cuff blood pressure (BP), heart weight, cardiomyocyte cross-sectional area (CSA) and the ratio of fibrotic area were evaluated and compared in all animals.
Results: As expected, animals with CKD had a significantly elevated serum creatinine (p<0.001) and BP (p<0.001) both of which were improved with LCZ696 treatment (creatinine: p<0.05, BP: p<0.001). While the serum creatinine was significantly better in the LCZ group compared to VAL (p<0.05), both groups had similar blood pressures by the end of the study. The ratio of heart weight to body weight was significantly less in the LCZ group when compared to nontreated CKD (p<0.01). While the CSA was reduced in both LCZ and VAL group when compared with untreated CKD (LCZ: p<0.001, VAL: p<0.05), the LCZ696- treated animals had a lower CSA compared to animals treated with valsartan alone (p<0.05). Meanwhile, both LCZ and VAL groups had significantly lower fibrotic index compared to untreated CKD (LCZ: p<0.05, VAL: p<0.01).
Conclusions: LCZ696 therapy in a rat model of CKD was associated with reduced myocardial hypertrophy and fibrosis in addition to improved renal function. Antihypertrophic benefit of LCZ over VAL was independent of a further BP reduction. Future clinical studies are needed to evaluate the role of this promising agent in treatment of CKD-associated cardiovascular remodeling.
Author Disclosures: Y. Suematsu: None. A. Nunes: None. M. Khazaeli: None. W. Jing: None. M.L. Kashyap: None. N.D. Vaziri: None. H. Moradi: None.
- © 2016 by American Heart Association, Inc.