Published online Jul 15, 2022. doi: 10.4239/wjd.v13.i7.471
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
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.
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.