Renal Dysfunction in Cardiometabolic Disease: Implications of Inflammation and Oxidative Stress

Endothelial dysfunction is a major pathological mechanism implicated in the development and progression of cardiometabolic disease (CMD). Beyond the detrimental effects of endothelial dysfunction, inflammation, and oxidative stress have emerged as critical features of CMD that define chronic kidney disease, which is called cardiovascular-kidney-metabolic (CKM) syndrome. Predominant markers of inflammation, such as C-reactive protein, tumor necrosis factor-alpha, and interleukin-1β, are consistently associated with kidney failure in preclinical models and people with CKM. Similarly, important markers of oxidative stress, such as increased reactive oxygen species and depleted intracellular antioxidants, are consistent with pancreatic kidney damage in conditions of CKM. To improve CKM health and related outcomes in the population, there is a critical need for: (1) More clarity on the definition of CKM syndrome; (2) An approach to CKM staging that promotes prevention across the life course; (3) Prediction algorithms that include the exposures and outcomes most relevant to CKM health; and (4) Strategies for the prevention and management of cardiovascular disease in relation to CKM health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence.

The current topic explores preclinical and clinical research on the pathological implications of inflammation and oxidative stress during the development of renal dysfunction in CKM. Moreover, important molecular mechanisms and relevant biomarkers involved in this process will be discussed to divulge a pathological link between inflammation and oxidative stress during kidney failure in CKM.

Our research topic will cover the following key areas but is not limited to:

• Investigation of potentially novel mechanisms and associations between oxidative stress, inflammation, and CKM
• Machine learning as a tool for the identification and experimental validation of potential novel molecular biomarkers of CKM
• Use of combinations of biomarkers and panels of biomarkers for CKM risk prediction, diagnosis, and prognosis
• Efforts in targeting inflammation and oxidative stress for the management of CKM aim to provide unified and personalized care for those dealing with these conditions.
• Customized treatment plans for CKM, with a special focus on controlling inflammation and oxidative stress and improving health outcomes in people living with CKM (PLWCKM).
• Investigating lifestyle interventions, pharmacological treatments, and regular monitoring methods is essential for effective management in PLWCKM.
• Research and Innovation, supporting ongoing research endeavors aimed at advancing understanding and developing innovative interventions for PLWCKM, with a particular emphasis on reducing inflammation and oxidative stress.