Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study.
Aldosterone
Angiotensin
Diabetes mellitus
Mineralocorticoid receptor antagonist
Renin
Renin–angiotensin–aldosterone system
Journal
Diabetes therapy : research, treatment and education of diabetes and related disorders
ISSN: 1869-6953
Titre abrégé: Diabetes Ther
Pays: United States
ID NLM: 101539025
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
29
05
2021
accepted:
07
07
2021
pubmed:
6
8
2021
medline:
6
8
2021
entrez:
5
8
2021
Statut:
ppublish
Résumé
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. 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. 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). Combined eplerenone and ACEi therapy increases Ang-(1-7) levels in patients with CKD indicating a unique nephroprotective RAAS pattern with considerable therapeutic implications.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 34351585
doi: 10.1007/s13300-021-01118-7
pii: 10.1007/s13300-021-01118-7
pmc: PMC8384966
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2485-2498Informations de copyright
© 2021. The Author(s).
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