Renal intrinsic cells remodeling in diabetic kidney disease and the regulatory effects of SGLT2 Inhibitors

Diabetic kidney disease (DKD) is a prevalent complication of diabetes and a major secondary factor leading to end-stage renal disease. The kidney, a vital organ, is composed of a heterogeneous group of intrinsic cells, including glomerular endothelial cells, podocytes, mesangial cells, tubular epithelial cells, and interstitial fibroblasts. In the context of DKD, hyperglycemia elicits direct or indirect injury to these intrinsic cells, leading to their structural and functional changes, such as cell proliferation, apoptosis, and transdifferentiation. The dynamic remodeling of intrinsic cells represents an adaptive response to stimulus during the pathogenesis of diabetic kidney disease. However, the persistent stimulus may trigger an irreversible remodeling, leading to fibrosis and functional deterioration of the kidney. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of hypoglycemic drugs, exhibit efficacy in reducing blood glucose levels by curtailing renal tubular glucose reabsorption. Furthermore, SGLT2 inhibitors have been shown to modulate intrinsic cell remodeling in the kidney, ameliorate kidney structure and function, and decelerate DKD progression. This review will elaborate on the intrinsic cell remodeling in DKD and the underlying mechanism of SGLT2 inhibitors in modulating it from the perspective of the renal intrinsic cell, providing insights into the pathogenesis of DKD and the renal protective action of SGLT2 inhibitors.