Endocrinology and Metabolism

Review Articles

Diabetes, obesity and metabolism
Intrarenal Hemodynamic Mechanisms of Kidney Protection by Nonsteroidal Mineralocorticoid Receptor Antagonists: Eun Sil Koh, So Young Lee, Doan Thi Thien Hao, Sungjin Chung; Endocrinol Metab. 2026;41(3):337-350. Published online June 16, 2026; DOI: https://doi.org/10.3803/EnM.2026.3093

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Abstract PDF PubReader ePub: Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), especially finerenone, have shown significant cardiorenal benefits in patients with chronic kidney disease (CKD). Clinical trials consistently report reductions in albuminuria and improved renal outcomes; however, the specific intrarenal hemodynamic mechanisms remain partially understood. nsMRAs lower albuminuria, a critical surrogate marker for CKD progression, with early reductions contributing significantly to renal benefits. These agents produce mild natriuretic effects by inhibiting aldosterone-mediated sodium reabsorption in the distal nephron, resulting in a slight reduction in extracellular volume. Additionally, nsMRAs may impact glomerular hemodynamics by mitigating aldosterone-induced constriction of the efferent arterioles and restoring tubuloglomerular feedback, while also modulating connecting tubule glomerular feedback. Collectively, these effects may contribute to lowering intraglomerular pressure and attenuating glomerular hyperfiltration. However, current evidence does not definitively show that nsMRAs are superior to steroidal mineralocorticoid receptor antagonists in correcting hyperfiltration. Their clinical benefits seem to arise from enhanced safety, tolerability, and sustained therapeutic use. This narrative review synthesizes existing clinical and experimental evidence on the intrarenal hemodynamic effects of nsMRAs, emphasizing their roles in sodium handling, natriuresis, and regulation of intraglomerular pressure.

Diabetes, obesity and metabolism
Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis: Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung; Endocrinol Metab. 2023;38(4):359-372. Published online July 24, 2023; DOI: https://doi.org/10.3803/EnM.2023.1764

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When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.

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