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Kovarik JJ, Kaltenecker CC, Domenig O, et al. Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study. Diabetes Ther. 2021;12(9):2485-2498doi: 10.1007/s13300-021-01118-7.
Kovarik, J. J., Kaltenecker, C. C., Domenig, O., Antlanger, M., Poglitsch, M., Kopecky, C., & Säemann, M. D. (2021). Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study. Diabetes therapy : research, treatment and education of diabetes and related disorders, 12(9), 2485-2498. https://doi.org/10.1007/s13300-021-01118-7
Kovarik, Johannes J, et al. "Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study." Diabetes therapy : research, treatment and education of diabetes and related disorders vol. 12,9 (2021): 2485-2498. doi: https://doi.org/10.1007/s13300-021-01118-7
Kovarik JJ, Kaltenecker CC, Domenig O, Antlanger M, Poglitsch M, Kopecky C, Säemann MD. Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study. Diabetes Ther. 2021 Sep;12(9):2485-2498. doi: 10.1007/s13300-021-01118-7. Epub 2021 Aug 05. PMID: 34351585; PMCID: PMC8384966.
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Diabetes Ther. 2021 Sep;12(9):2485-2498. doi: 10.1007/s13300-021-01118-7. Epub 2021 Aug 05.

Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study.

Diabetes therapy : research, treatment and education of diabetes and related disorders

Johannes J Kovarik, Christopher C Kaltenecker, Oliver Domenig, Marlies Antlanger, Marko Poglitsch, Chantal Kopecky, Marcus D Säemann

Affiliations

  1. Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. [email protected].
  2. Department of Pathology, Medical University Vienna, Vienna, Austria.
  3. Attoquant Diagnostics GmbH, Vienna, Austria.
  4. 2nd Department of Internal Medicine, Kepler University Hospital, Med Campus III, Linz, Austria.
  5. School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
  6. 6th Medical Department with Nephrology and Dialysis, Clinic Ottakring, Vienna, Austria.
  7. Sigmund-Freud University, Vienna, Austria.

PMID: 34351585 PMCID: PMC8384966 DOI: 10.1007/s13300-021-01118-7

Abstract

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.

© 2021. The Author(s).

Keywords: Aldosterone; Angiotensin; Diabetes mellitus; Mineralocorticoid receptor antagonist; Renin; Renin–angiotensin–aldosterone system

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