Novel Pathophysiologic Mechanisms and Reno-Protective Pharmacotherapies in Diabetic Kidney Disease – Volume 2

Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease worldwide. Its progression is driven by a constellation of intertwined pathophysiologic mechanisms, including glomerular hyperfiltration, activation of the renin–angiotensin–aldosterone system (RAAS), accumulation of advanced glycation end products, polyol pathway activation, epithelial–mesenchymal transition, thrombomodulin receptor signaling, and metabolic memory resulting from epigenetic alterations. These diverse molecular pathways have provided multiple therapeutic targets; however, for decades, RAAS inhibition remained the only clinically effective intervention for DKD.

The therapeutic landscape has since evolved dramatically. In 2019, sodium–glucose cotransporter-2 inhibitors emerged as the first agents to confer both renal and cardiovascular protection in DKD. Subsequently, the FIDELIO-DKD trial (2020) revitalized interest in mineralocorticoid receptor blockade with finerenone, demonstrating robust cardiorenal benefits. The recent FLOW trial (2024) on glucagon-like peptide-1 (GLP-1) receptor agonists has further expanded the therapeutic armamentarium, and several ongoing mechanistic and clinical trials continue to reshape the field.

Building upon the success of Volume 1, this second volume of the Research Topic aims to advance understanding of the complex molecular underpinnings of DKD and the development of next-generation reno-protective pharmacotherapies. We welcome manuscripts encompassing original research, systematic reviews, mini-reviews, hypotheses, theories, clinical trials, and perspectives, covering (but not limited to) the following themes:

1. Novel pathogenic mechanisms in DKD – insights from animal and human studies.

2. Non-diabetic kidney disease in patients with diabetes – diagnostic challenges and prognostic implications.

3. Pharmacokinetics, safety, and efficacy of newer agents in DKD.

4. Emerging reno-protective therapies in DKD – mechanistic Phase 2 and clinical Phase 3 trials.

This collection seeks to foster translational dialogue between basic scientists, pharmacologists, and clinicians toward redefining therapeutic strategies for diabetic kidney disease.

Topic Coordinator, Dr. Elenjickal, is supported by an educational grant from Pfizer.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: reno-protective therapies, Diabetic kidney disease, cardiorenal outcomes, RAAS, ACE inhibitors, mineralocorticoid receptor antagonists, oxidative stress, inflammation, epigenetic alterations, biomarkers, precision medicine, network pharmacology

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.