Diabetic Kidney Disease (DKD), a severe complication of diabetes mellitus, and a leading cause of end-stage kidney disease affecting more than 100 million people globally. The increasing prevalence of obesity and diabetes escalates the risks, underlining the interwoven complexities of chronic kidney disease (CKD) and cardiovascular diseases in these patients. Despite therapeutic advances like glucose regulation and hypertension management via renin-angiotensin-aldosterone system inhibitors, a significant proportion of diabetics progress towards kidney disease, underscoring a pressing need to delve deeper into the molecular underpinnings to curb this trajectory and improve patient outcomes.

This Research Topic aims to dissect the complex molecular pathways implicated in the development and aggravation of DKD. By focusing on the interplay of metabolic, hemodynamic, and inflammatory mechanisms and their role in the pathological landscape of DKD, we seek to unveil targeted therapeutic strategies that can dramatically alter the clinical outcomes for afflicted individuals.

To gather further insights into the molecular dimensions of DKD and their impacts on DKD pathogenesis, as well as highlight potential clinical applications and therapeutic targets, we welcome articles addressing, but not limited to, the following themes:

- Broadly, the molecular mechanisms leading to the development and progression of DKD.
- Role of circulating factors contributing to DKD.
- Epigenetic mechanisms causing dysfunction in DKD and targeting epigenetic modifications for therapeutic intervention.
- Role of cell-cell interactions and intercellular communication in kidney repair and regeneration in DKD progression.
- Innate immunity mechanisms involved in DKD pathogenesis, including macrophage infiltration, one of the hallmarks of DKD.
- Impacts of molecular pathways on oxidative stress and kidney function in DKK.
- Role of molecular pathways in protein modifications and cellular stress in DKD.
- Mechanisms of advanced glycation end products (AGEs) formation and their effects on kidney cells.
- Activation of protein kinase C (PKC) isoforms and their contributions to glomerulosclerosis.
- Effects of lipid accumulation in podocytes, endothelial cells, and proximal tubule cells.
- Mitochondrial dysfunction resulting from dysregulated lipid metabolism.
- Role of reactive oxygen species (ROS) in kidney damage and DKD progression.
- AMP-activated protein kinase (AMPK) signaling in regulating cellular energy homeostasis.
- Crosstalk between fibrotic and inflammatory pathways in DKD progression.
- Interventions targeting metabolic pathways to mitigate DKD progression.
- Mechanisms of RAAS in DKD and its therapeutic targeting.
- Benefits and limitations of sodium-glucose cotransporter inhibitors (SGLT2 inhibitors) in DKD.
- Novel drug targets identified through molecular pathway research.
- Advances in gene therapy and molecular interventions for DKD.
- Development of combination therapies addressing multiple pathways.

Dr Fedeles reports being employed by the Critical Path Institute; reports honoraria from Vertex; has filed patents and received royalties on inventions from Yale University; sits on the Scientific Advisory Boards of Retex Pharma and Renasant Bio; received research funding from Retex Pharma; owns equity in Targetsite Therapeutics. He reports no conflict with respect to the current Frontiers engagement.

Dr. Pedigo reports being employed by Omega Theraputics, but reports no conflicts of interest with respect to the current Frontiers Research Topic.

Dr. Ettou reports being employed by Ingenia Therapeutics, but reports no conflicts of interest with respect to the current Frontiers Research Topic.

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