Key result
Eplerenone on top of ACE inhibitor therapy significantly increased plasma Ang-(1-7) levels (median 22.2 vs 6.3 pmol/l) and upregulated renin, Ang I, and aldosterone in patients with diabetic kidney disease.
Why the study?
The detailed effects of adding mineralocorticoid receptor antagonists to conventional RAAS blockade on key RAAS effectors had not been elucidated.
Does eplerenone added to ACE inhibitor therapy alter systemic RAAS metabolism and angiotensin profiles in patients with diabetic kidney disease?
RCT (n=15)
Placebo-controlled
Randomized
No
Does eplerenone added to ACE inhibitor therapy alter systemic RAAS metabolism and angiotensin profiles in patients with diabetic kidney disease?
Absolute Event Rate: 22.2% vs 6.3%
p-value: p=<0.05
Adding eplerenone to ACE inhibitor therapy in diabetic kidney disease upregulates the nephroprotective alternative RAAS effector Ang-(1-7), providing a potential molecular mechanism for its renoprotective effects.
Supports adding eplerenone to ACE inhibitors in diabetic kidney disease; extends mechanistic evidence for alternative RAAS activation.
BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) is the cornerstone of antihypertensive treatment in patients with chronic kidney disease (CKD) and diabetes mellitus. Mineralocorticoid receptor antagonists (MRA) on top of conventional RAAS blockade confer cardio- and renoprotective effects. Yet, the detailed effects of this therapeutic approach on key RAAS effectors have not been elucidated to date. METHODS: In this exploratory placebo-controlled study, 15 patients with CKD stages 2-3 and albuminuria due to diabetic kidney disease (DKD) were randomized to receive the MRA eplerenone or placebo in addition to ACEi therapy. Employing mass-spectrometry, we quantified plasma angiotensin levels [Ang I, Ang II, Ang-(1-7), Ang-(1-5), Ang III, Ang IV], renin and aldosterone in patients before and after 8 weeks of MRA treatment. RESULTS: While blood pressure and kidney function were similar in the placebo and eplerenone treatment group during the study period, distinct differences in RAAS regulation occurred: eplerenone treatment resulted in an increase in plasma renin activity, Ang I and aldosterone concentrations, indicating global RAAS activation. In addition, eplerenone on top of ACEi profoundly upregulated the alternative RAAS effector Ang-(1-7). CONCLUSIONS: Combined eplerenone and ACEi therapy increases Ang-(1-7) levels in patients with CKD indicating a unique nephroprotective RAAS pattern with considerable therapeutic implications.
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Kovarík et al. (2021) conducted an RCT in Diabetic Kidney Disease (n=15). Eplerenone vs. Placebo was evaluated on Plasma Ang-(1-7) concentration (p=<0.05). Eplerenone on top of ACE inhibitor therapy significantly increased plasma Ang-(1-7) levels (median 22.2 vs 6.3 pmol/l) and upregulated renin, Ang I, and aldosterone in patients with diabetic kidney disease.
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