About this Research Topic
Diabetic Kidney Disease (DKD) is a severe complication of diabetes mellitus and a leading cause of end-stage kidney disease affecting more than 100 million people worldwide. This number is expected to increase with the growing prevalence of obesity and diabetes, two major causes of chronic kidney disease (CKD). CKD and cardiovascular disease (CVD) have a significant inter-relationship in patients with diabetes. Controlling blood pressure, dyslipidemia, and glucose levels is a common treatment approach to managing CVD risk in patients with CKD and diabetes. Despite advances in diabetes management, including tight glucose control and blood pressure regulation through renin-angiotensin-aldosterone system inhibitors, the progression of kidney disease remains prevalent among diabetic patients. Indeed, about one-third of diabetic patients will develop kidney disease. Given the prevalence of DKD, understanding the molecular mechanisms underlying DKD is crucial for developing new therapeutic strategies and improving patient outcomes.
The pathogenesis of diabetic and obesity-related kidney disease evolved multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways and others play a vital role in the initiation and progression of DKD.
Hyperglycemia, insulin resistance, and dyslipidemia significantly stress the kidney, disrupting the metabolic balance in podocytes and endothelial cells, and imposing additional burdens on proximal tubule cells. Initially, cells adapt with hypertrophy and actin cytoskeleton rearrangement. As DKD progresses, mitochondrial dysfunction emerges, increasing oxidative stress and triggering inflammatory pathways, ultimately leading to declining kidney function and fibrosis. Interventions such as renin-angiotensin system blockade and sodium-glucose cotransporter targeting have shown benefits by offering cellular protection and slowing kidney function deterioration. Recent evidence highlights the roles of epigenetic changes, microvascular complications, and cellular metabolic dysfunction, suggesting that modulation of these pathways may prevent or slow kidney disease progression. This Research Topic aims to address the complex molecular pathways implicated in the pathogenesis of DKD.
We invite contributions that delve into the molecular signaling pathways involved in DKD. Authors are encouraged to submit manuscripts that advance our understanding of DKD pathogenesis and highlight potential clinical applications and therapeutic targets. The scope includes but is not limited to papers focusing on:
• 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 DKD.
• 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.
The pathogenesis of diabetic and obesity-related kidney disease evolved multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways and others play a vital role in the initiation and progression of DKD.
Hyperglycemia, insulin resistance, and dyslipidemia significantly stress the kidney, disrupting the metabolic balance in podocytes and endothelial cells, and imposing additional burdens on proximal tubule cells. Initially, cells adapt with hypertrophy and actin cytoskeleton rearrangement. As DKD progresses, mitochondrial dysfunction emerges, increasing oxidative stress and triggering inflammatory pathways, ultimately leading to declining kidney function and fibrosis. Interventions such as renin-angiotensin system blockade and sodium-glucose cotransporter targeting have shown benefits by offering cellular protection and slowing kidney function deterioration. Recent evidence highlights the roles of epigenetic changes, microvascular complications, and cellular metabolic dysfunction, suggesting that modulation of these pathways may prevent or slow kidney disease progression. This Research Topic aims to address the complex molecular pathways implicated in the pathogenesis of DKD.
We invite contributions that delve into the molecular signaling pathways involved in DKD. Authors are encouraged to submit manuscripts that advance our understanding of DKD pathogenesis and highlight potential clinical applications and therapeutic targets. The scope includes but is not limited to papers focusing on:
• 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 DKD.
• 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.
Keywords: Diabetic Kidney Disease, Diabetes Mellitus, Hyperglycemia, Renin-Angiotensin-Aldosterone System Inhibitors, Oxidative Stress, Mitochondrial Dysfunction, Sodium-Glucose Cotransporter Inhibitors, Podocyte dysfunction, Tubular dysfunction, EC dysfunction, Podocyte Injury, Innate immunity, Dyslipidemia
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
