Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

Hou, Yi; Zheng, Cai Mei; Yen, Tzung Hai; Lu, Kuo Cheng

doi:10.3390/ijms21217833

Cited by 55 publications

(46 citation statements)

References 165 publications

(184 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another possible explanation is that SGLT2-sympathetic inhibition was mediated by the central autonomic system, as suggested by the recent findings. By fact, SGLT2is inhibit central sympathetic as well as autonomic activity; however, the underlying mechanisms have not yet been clarified [ 50 , 51 ].…”

Section: Mechanisms Of Renal Protection With Sglt2mentioning

confidence: 99%

“…In the first SGLT2is CVOT EMPA–REG OUTCOME [ 51 , 55 ], patients with type 2 diabetes at high-risk of CV were required to have an estimated glomerular filtration rate (eGFR) above 30 mL/min/1.73 m 2 ; the mean eGFR was 74 ± 21 mL/min/1.73 m 2 and 25.9% of patients had eGFR < 60 mL/min/1.73 m 2 . As for albuminuria, 59.4% patients were normoalbuminuric, 29% microalbuminuric, and 11% macroalbuminuric.…”

Section: Renal Protection By Sglt2is: Data From Cvotsmentioning

confidence: 99%

See 1 more Smart Citation

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

Leoncini

Russo

Bussalino

et al. 2021

IJMS

View full text Add to dashboard Cite

In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs.

show abstract

Section: Mechanisms Of Renal Protection With Sglt2mentioning

confidence: 99%

Section: Renal Protection By Sglt2is: Data From Cvotsmentioning

confidence: 99%

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

Leoncini

Russo

Bussalino

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…It is located in the S1–2 segment of the proximal convoluted tubules and is responsible for reabsorption of 90% of glucose filtered through the glomerulus ( 125 ). Multiple mechanisms are explored involving the kidney protection of SGLT2 inhibition, mainly characterized into (1) attenuation of proximal tubular oxidative stress, mitochondrial morphology, modulation of key metabolism and reabsorptive proteins, pro-inflammatory and profibrotic cytokines, and improvement of tubulointerstitial fibrosis; (2) through activation of tubuloglomerular feedback to regulate glomerular hemodynamic stability and metabolic effects ( 126 , 127 ). Table 2 summarizes the underlying mechanism of kidney protection by SGLT2 inhibition in DM reported in recent years.…”

Section: Renal Tubule-targeting Therapeutics: a New Era For Dkd Managementmentioning

confidence: 99%

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

et al. 2021

View full text Add to dashboard Cite

Over decades, substantial progress has been achieved in understanding the pathogenesis of proteinuria in diabetic kidney disease (DKD), biomarkers for DKD screening, diagnosis, and prognosis, as well as novel hypoglycemia agents in clinical trials, thereby rendering more attention focused on the role of renal tubules in DKD. Previous studies have demonstrated that morphological and functional changes in renal tubules are highly involved in the occurrence and development of DKD. Novel tubular biomarkers have shown some clinical importance. However, there are many challenges to transition into personalized diagnosis and guidance for individual therapy in clinical practice. Large-scale clinical trials suggested the clinical relevance of increased proximal reabsorption and hyperfiltration by sodium-glucose cotransporter-2 (SGLT2) to improve renal outcomes in patients with diabetes, further promoting the emergence of renal tubulocentric research. Therefore, this review summarized the recent progress in the pathophysiology associated with involved mechanisms of renal tubules, potential tubular biomarkers with clinical application, and renal tubular factors in DKD management. The mechanism of kidney protection and impressive results from clinical trials of SGLT2 inhibitors were summarized and discussed, offering a comprehensive update on therapeutic strategies targeting renal tubules.

show abstract

“… 9 , 12 SGLT2 inhibitors have been shown to inhibit the sodium proton channel (NHE) in the cardiac myocytes that eventually leads to the reduction in intracellular calcium and mitochondria-induced cellular damage that lies at the heart of myocardial remodeling. 13 , 14 …”

Section: Molecular Mechanisms Of Dapagliflozinmentioning

confidence: 99%

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence

Gupta¹,

Rao²,

Manek³

et al. 2021

TCRM

View full text Add to dashboard Cite

The burden and cost of heart failure management, primarily in the form of hospitalization in the setting of decompensated heart failure, continue to be some of the biggest clinical challenges in cardiovascular medicine. In recently published randomized controlled trials, including DAPA-HF, sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin was shown to reduce hospitalization from heart failure or mortality associated with cardiovascular causes, when added to existing guideline-directed medical therapy. The American College of Cardiology (ACC) released a Clinical Pathway guideline that recommends the use of dapagliflozin in clinical management of heart failure, with or without diabetes. Furthermore, the results of the DAPA-CKD trial broaden the utility of dapagliflozin as a therapeutic option in patients with advanced kidney disease. In this article, the authors explore the existing evidence on dapagliflozin in heart failure with reduced ejection fraction and highlight the need for further research on uses of dapagliflozin in the world of heart failure.

show abstract

Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

Cited by 55 publications

References 165 publications

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence

Contact Info

Product

Resources

About