Editorial
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2022; 13(7): 471-481
Published online Jul 15, 2022. doi: 10.4239/wjd.v13.i7.471
Renin-angiotensin system blockers-SGLT2 inhibitors-mineralocorticoid receptor antagonists in diabetic kidney disease: A tale of the past two decades!
Awadhesh Kumar Singh, Ritu Singh
Awadhesh Kumar Singh, Ritu Singh, Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata 700013, West Bengal, India
Author contributions: Singh AK designed the research; Singh R performed the research, Singh AK and Singh R analyzed the data; Singh AK wrote the editorial; Singh R revised the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Awadhesh Kumar Singh, MBBS, MD, DM, Consultant Physician-Scientist, Intermediate Editor, Senior Postdoctoral Fellow, Senior Researcher, Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, 133A, Lenin Sarani, Kolkata 700013, West Bengal, India. draksingh_2001@yahoo.com
Received: March 11, 2022
Peer-review started: March 11, 2022
First decision: April 18, 2022
Revised: April 19, 2022
Accepted: June 18, 2022
Article in press: June 18, 2022
Published online: July 15, 2022
Processing time: 121 Days and 15.2 Hours
Abstract

Several pharmacological agents to prevent the progression of diabetic kidney disease (DKD) have been tested in patients with type 2 diabetes mellitus (T2DM) in the past two decades. With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001, no other pharmacological agent tested in the past two decades have shown any clinically meaningful result. Recently, the sodium-glucose cotransporter-2 inhibitor (SGLT-2i), canagliflozin, has shown a significant reduction in the composite of hard renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of renin-angiotensin system blocker use. Another SGLT-2i, dapagliflozin, has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease (CKD), regardless of T2DM status. Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM. However, the full results of this trial have not yet been published. While the use of older steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes, a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM, with reasonably acceptable side effects.

Keywords: Renin-angiotensin system blockers; SGLT-2 inhibitors; Mineralocorticoid receptor antagonist; Diabetic kidney disease; Chronic kidney disease; Renal outcomes; Cardiovascular outcomes

Core Tip: Angiotensin receptor blockers were the first drug class to show a conclusive benefit in preventing diabetic kidney disease (DKD) progression through two randomized trials IDNT and RENAAL in 2001. Several newer pharmacological agents have been tested in DKD in the past 20 years without much success. Notably, recently conducted renal outcome trials of sodium-glucose cotransporter-2 inhibitors in patients with DKD such as CREDENCE, DAPA-CKD, and EMPA-KIDNEY have shown significant improvement in disease progression. Similarly, recent trials of the non-steroidal mineralocorticoid receptor antagonist finerenone (FIDELIO-DKD and FIGARO-DKD) have shown significant improvement in both renal and cardiac endpoints in DKD.