Treatment of Type 2 diabetic nephropathy mice with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) and/or angiotensin receptor blocker (ARB)

Abstract

In diabetes, glomerular hyper-filtration appears to be driven by SGLT2. Hyper-reabsorption of glucose and sodium in the proximal tubule remarkably reduces sodium delivery to the distal tubule, which is incorrectly sensed by the JGA and consequently leads to limited tubuloglomerular feedback, resulting in increased intraglomerular pressure and glomerular hyper-filtration.

Increasing evidence has reported renal protection after kidney disease-targeted interventions, such as RAAS modulators and SGLT2i, indicating the importance of reducing intraglomerular pressure, which is essential for the preservation of kidney function. This study aims to underlie the mechanism behind the renal protective benefits of SGLT2i and RAAS modulators.

The major findings of this study are summed up as following: 1.12-weeks SGLT2i and/or ARB treatments showed tendencies to attenuate the albuminuria progression in DN mice. 2. Primary snRNA-seq data were generated with 5 female DN kidneys (n=1 per condition). 3. Differential expression analysis suggested that the SGLT2i and/or ARB treatments had significant effects on different cell types in the kidney. 4. Combined treatment showed stronger effects on kidney cells compared to SGLT2i treatment.