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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
The systemic nature of CKD
Carmine Zoccali1, Raymond Vanholder2, Ziad A Massy3,4,5,6,7
1CNR-IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension Unit, Ospedali Riuniti 89124 Reggio Calabria, Italy.
Abstract:
The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.
Insights
Chronic kidney disease (CKD) is a systemic condition affecting multiple organs. Understanding these complex interactions using systems biology can reveal new targets for CKD prevention and treatment.
Area of Science:
- Nephrology
- Systems Biology
- Genomics
Background:
- Chronic kidney disease (CKD) definition and staging are key nephrology advancements.
- Previous research on CKD's organ interactions used a limited, two-organ approach due to technological constraints.
- Emerging evidence points to CKD's complex, systemic nature involving integrated biological processes.
Purpose of the Study:
- To highlight the complex and systemic nature of chronic kidney disease.
- To discuss how a diseased kidney disrupts integrated biological systems.
- To advocate for a systems biology approach to study CKD pathophysiology.
Main Methods:
- Review of experimental and clinical studies from the last two decades.
- Analysis of organ interactions, focusing on energy balance, innate immunity, and neuroendocrine signaling.
- Discussion of omics techniques for a systems biology approach.
Main Results:
- CKD disrupts integrated biological systems, leading to a high-risk phenotype.
- This phenotype includes inflammation, protein-energy wasting, and nervous system dysfunction.
- CKD is associated with cardiopulmonary, vascular, and bone diseases.
Conclusions:
- CKD is a systemic disease with widespread effects beyond the kidneys.
- A systems biology approach is crucial for understanding CKD's complex pathophysiology.
- Targeting disrupted pathways identified through systems biology may lead to novel CKD prevention and therapies.
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