The effects of sacubitril/valsartan compared to valsartan in experimentally induced chronic kidney disease

Abstract

Sacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker which simultaneously potentiates the beneficial effects of natriuretic peptides while blocking angiotensin II accumulation. Numerous studies suggest that sacubitril/valsartan has better renal protective effects compared to valsartan but the evidence remains inconsistent. This study compared renal and blood pressure (BP)-lowering effects of sacubitril/valsartan versus valsartan in rats with adenine-induced chronic kidney disease (CKD). This model replicates slow progression and structural and functional characteristics of human CKD. Male Wistar rats (n = 24) were divided into four groups and treated for 35 days as follows: group 1 served as control; group 2 received 0.25% adenine; group 3 received adenine plus sacubitril/valsartan; group 4 received adenine plus valsartan. Adenine significantly increased systolic BP. It also significantly increased the urinary albumin/creatinine ratio, N-acetyl-β-D-glucosaminidase (NAG), plasma urea, creatinine, uric acid, and neutrophil gelatinase-associated lipocalin (NGAL) while reducing creatinine clearance. Additionally, adenine significantly increased inflammatory markers, decreased antioxidant activity, and induced tubular necrosis, dilatation, and interstitial inflammation. Sacubitril/valsartan significantly reduced systolic BP, with greater effects than valsartan. Both treatments reversed adenine-induced alterations in urinary albumin/creatinine ratio, NAG, plasma urea, creatinine, NGAL, and creatinine clearance, with more pronounced improvements in urea, NAG, and creatinine clearance observed with valsartan. Furthermore, both treatments ameliorated inflammatory and antioxidant changes to a comparable extent. Both treatments showed histopathological improvements, but these were more marked with valsartan. To conclude, both sacubitril/valsartan and valsartan effectively mitigated adenine-induced CKD changes, with sacubitril/valsartan producing greater systolic BP reduction and valsartan showing more pronounced renoprotective effects.