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.
Chronic kidney disease (CKD) is the most common cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM). CKD increases the risk of cardiovascular diseases; therefore, its prevention and treatment are important. The prevention of diabetic kidney disease (DKD) can be achieved through intensive glycemic control and blood pressure management. Additionally, DKD treatment aims to reduce albuminuria and improve kidney function. In patients with T2DM, renin-angiotensin-aldosterone system inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists can delay the progression of DKD. Hence, there is a need for novel treatments that can effectively suppress DKD progression. Finerenone is a first-in-class nonsteroidal mineralocorticoid receptor antagonist with clinically proven efficacy in improving albuminuria, estimated glomerular filtration rate, and risk of cardiovascular events in early and advanced DKD. Therefore, finerenone is a promising treatment option to delay DKD progression. This article reviews the mechanism of renal effects and major clinical outcomes of finerenone in DKD.
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Over the last 5 years there have been many new developments in the management of diabetic kidney disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially used for glycemic control, but more recent studies have now shown that their benefits extend to cardiovascular and kidney outcomes. The recent addition of data on the novel mineralocorticoid receptor antagonist (MRA) gives us another approach to further decrease the residual risk of diabetic kidney disease progression. In this review we describe the mechanism of action, key studies, and possible adverse effects related to these three classes of medications. The management of type 2 diabetes now includes an increasing number of medications for the management of comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors, GLP-1 RA and MRAs in patients with type 2 diabetes for heart and kidney protection.
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