Combined sodium glucose co-transporter-2 inhibitor and angiotensin-converting enzyme inhibition upregulates the renin-angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double-blind, placebo-controlled exploratory trial.
ACE inhibition
SGLT-2 inhibition
angiotensins
chronic kidney disease
empagliflozin
renin-angiotensin system activation
type 2 diabetes mellitus
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
09
12
2021
received:
07
09
2021
accepted:
01
01
2022
pubmed:
6
1
2022
medline:
8
4
2022
entrez:
5
1
2022
Statut:
ppublish
Résumé
Sodium glucose co-transporter-2 inhibitors (SGLT-2i) improve cardiorenal outcomes in patients with chronic kidney disease (CKD), with and without type 2 diabetes. The molecular mechanisms underlying these pleiotropic effects remain unclear, yet it is speculated that SGLT-2i elicit a neurohormonal modulation resulting in renin-angiotensin system (RAS) activation. We hypothesized that combined SGLT-2 and angiotensin-converting enzyme inhibition (ACEi) favours RAS regulation towards the beneficial angiotensin-(1-7)-driven axis. This randomized controlled prospective study investigated the effect of 12 weeks treatment with the SGLT-2i empagliflozin on top of ACEi on the molecular RAS dynamics in 24 diabetic and 24 non-diabetic patients with CKD. Systemic RAS peptides were quantified by mass spectrometry. In patients with type 2 diabetes, combined SGLT-2i and ACEi significantly upregulated plasma renin activity [pre-treatment median and interquartile range 298.0 (43.0-672.0) pmol/L versus post-treatment 577.0 (95.0-1543.0) pmol/L; p = .037] and angiotensin I levels [pre-treatment 289.0 (42.0-668.0) pmol/L versus post-treatment 573.0 (93.0-1522.0) pmol/L; p = .037], together with a significant increase of angiotensin-(1-7) levels [pre-treatment 14.0 (2.1-19.0) pmol/L versus post-treatment 32.0 (5.7-99.0) pmol/L; p = .012]. Empagliflozin treatment resulted in a 1.5 to 2-fold increase in main RAS peptides in patients with diabetes compared with placebo. No significant effect of empagliflozin on top of ACEi on RAS peptides was found in patients with CKD without diabetes. A distinct RAS modulation by SGLT-2i occurs in diabetic kidney disease reflected by enhancement of the beneficial angiotensin-(1-7) providing a molecular background for this renoprotective therapeutic approach.
Identifiants
pubmed: 34984822
doi: 10.1111/dom.14639
pmc: PMC9305250
doi:
Substances chimiques
Angiotensins
0
Sodium-Glucose Transporter 2 Inhibitors
0
Sodium
9NEZ333N27
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
816-826Informations de copyright
© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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