Recent Advancement of the Cardio-Renal Protective Effects of SGLT2 Inhibitors in People With and Without Diabetes

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Background

Diabetic kidney disease (DKD) has long been the center attention due to its progressive nature which determines patients’ prognosis. Indeed, DKD has become a main health concern in modern countries in the past decades. A plethora of evidence has emerged as to the cardio-renal protective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors as well as GLP-1 RA in the past several years. Together with the preceding clinical studies such as EMPA-REG OUTCOME and CREDENCE in diabetics, recent studies, DAPA-CKD, DAPA-HF and Emperor-Reduced and Emperor-Preserved have not only proven those previous findings but further extends its clinical indications to heart failure and CKD in the absence of diabetes mellitus (DM).

The underlying mechanisms of cardio-renal protective effects with SGLT2 inhibitors are multifactorial, and they are not always obviously clarified. The main mechanisms by which SGLT 2 inhibitors exert such beneficial effects may be accounted for by salt/water diuresis via SGLT2 and Na/H exchanger 3 (NHE3) inhibition, glucosuria-induced osmotic diuresis, and the subsequent optimization of the tubule-glomerular feedback (TGF) system in the kidney. Furthermore, improvement of renal interstitial congestion of the kidney with SGLT2 inhibitors undoubtedly contribute to renal protection. These results are suggestive that SGLT2 inhibitors may futuristically be classified as proximal tubules-acting diuretics. One can propose that we are obtaining another new efficacious therapeutic agents to retard the progression of DKD in addition to the already-known, and -established renal protective agents, ACE inhibitors and ARBs.

The aim and scope of this project is to discuss the presumable mechanisms of SGLT2 inhibitors exerting the cardio-renal protection not only in people with diabetes but those without, by addressing multiple different aspects mentioned hereafter. In order to fulfil the above-mentioned purpose, topics contributors may address include but are not limited to:

1. Discovery and identification of SGLT2 and its clinical application

2. Updating the large-scale studies of SGLT2 inhibitors in people with diabetes

3. Quoting the studies such as EMPA-REG, CANVAS, CREDENCE etc.

4. Mechanisms of Cardio protection with SGLT2 inhibitors

5. Mechanisms of Nephroprotection with SGLT2 inhibitors.

6. Possibilities of cardio-renal protection in people without diabetes

7. Current status of the multiple pharmacological interventions including SGLT2 inhibition, GLP-1 receptor agonism, RAS inhibition, MRA and ET antagonists in DKD.

8. Early application, primary prevention and/or dietary modulation of SGLT2 inhibition therapy beyond DM.

9. DAPA-CKD, and the therapeutic insights into non-diabetic CKD especially in patients with IgA nephropathy

Keywords: Diabetic Kidney Disease, SGLT2 Inhibitors, Cardio-Renal Protection

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