Combined sEH inhibition and RAS blockade improved survival, reduced albuminuria and kidney injury, and attenuated creatinine clearance decline compared to RAS blockade alone in rats with CKD.
Does the addition of a soluble epoxide hydrolase (sEH) inhibitor to RAS blockade improve renoprotection and survival in 5/6 nephrectomized Ren-2 transgenic hypertensive rats with established CKD?
Adding a soluble epoxide hydrolase inhibitor to standard RAS blockade provides superior renoprotection and survival benefits in a rat model of established chronic kidney disease.
BACKGROUND/AIMS: We found recently that increasing renal epoxyeicosatrienoic acids (EETs) levels by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, shows renoprotective actions and retards the progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). This prompted us to examine if additional protection is provided when sEH inhibitor is added to the standard renin-angiotensin system (RAS) blockade, specifically in rats with established CKD. METHODS: For RAS blockade, an angiotensin-converting enzyme inhibitor along with an angiotensin II type receptor blocker was used. RAS blockade was compared to sEH inhibition added to the RAS blockade. Treatments were initiated 6 weeks after 5/6 NX in TGR and the follow-up period was 60 weeks. RESULTS: Combined RAS and sEH blockade exhibited additional positive impact on the rat survival rate, further reduced albuminuria, further reduced glomerular and tubulointerstitial injury, and attenuated the decline in creatinine clearance when compared to 5/6 NX TGR subjected to RAS blockade alone. These additional beneficial actions were associated with normalization of the intrarenal EETs deficient and a further reduction of urinary angiotensinogen excretion. CONCLUSION: This study provides evidence that addition of pharmacological inhibition of sEH to RAS blockade in 5/6 NX TGR enhances renoprotection and retards progression of CKD, notably, when applied at an advanced stage.
Chábová et al. (Mon,) conducted a other in Chronic Kidney Disease. Combined sEH inhibition and RAS blockade vs. RAS blockade alone was evaluated on Survival rate, albuminuria, glomerular and tubulointerstitial injury, and creatinine clearance. Combined sEH inhibition and RAS blockade improved survival, reduced albuminuria and kidney injury, and attenuated creatinine clearance decline compared to RAS blockade alone in rats with CKD.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: