The Dynamics and Plasticity of Epigenetics in Diabetic Kidney Disease: Therapeutic Applications Vis-a-Vis

Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid retention, electrolyte imbalance, and an increased cardiovascular risk compared to those with normal renal function. The triggers for the irreversible renal function deterioration are multifactorial, and diabetes mellitus serves as a major contributor to the development of CKD, namely diabetic kidney disease (DKD). Recently, epigenetic dysregulation emerged as a pivotal player steering the progression of DKD, partly resulting from hyperglycemia-associated metabolic disturbances, rising oxidative stress, and/or uncontrolled inflammation. In this review, we describe the major epigenetic molecular mechanisms, followed by summarizing current understandings of the epigenetic alterations pertaining to DKD. We highlight the epigenetic regulatory processes involved in several crucial renal cell types: Mesangial cells, podocytes, tubular epithelia, and glomerular endothelial cells. Finally, we highlight epigenetic biomarkers and related therapeutic candidates that hold promising potential for the early detection of DKD and the amelioration of its progression.

Automated summary

Chronic kidney disease (CKD) is characterized by a gradual decline in glomerular filtration rate, resulting in adverse consequences such as fluid retention, electrolyte imbalance, and increased cardiovascular risk. Diabetes mellitus is a major contributor to the development of CKD, particularly diabetic kidney disease (DKD), which is influenced by epigenetic dysregulation triggered by metabolic disturbances, oxidative stress, and inflammation. This review provides an overview of the major epigenetic molecular mechanisms and summarizes current knowledge about epigenetic alterations in DKD. It highlights the importance of epigenetic regulation in various renal cell types and explores potential epigenetic biomarkers and therapeutic agents for early detection and management of DKD.