Lu Yue, Meng Linlin, Wang Xinlu, Zhang Yun, Zhang Cheng, Zhang Meng
State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Int J Mol Sci. 2025 Aug 17;26(16):7938. doi: 10.3390/ijms26167938.
Chronic kidney disease (CKD) is associated with a significantly elevated mortality rate, primarily due to cardiovascular disease (CVD), highlighting a complex bidirectional relationship between the two conditions. Life-threatening cardiovascular events occur despite control of the traditional risk factors, emphasizing the underlying role of non-traditional risk factors. CKD, causing mineral imbalance and the accumulation of uremic toxins due to a compromised ability to excrete waste products, imposes extra pressure on the cardiovascular system. The retention of mineral and uremic toxins, in turn, aggravates the progression of CKD. This review aims to elucidate the pathophysiological connections between CKD and CVD, with a particular focus on the metabolic regulatory mechanisms influenced by minerals such as calcium and phosphate, as well as uremic toxins. We review how these factors contributed to accelerated multi-organ damage through mechanisms such as inflammation, endothelial dysfunction, oxidative stress, and vascular calcification. In addition, we discuss the therapeutic strategies for specific uremic toxins and proposed directions for future investigations. This review provides insights into the complex interplay between metabolic dysregulation and cardiovascular outcomes in CKD patients, promoting the development of innovative therapeutic interventions, ultimately improving the prognosis and quality of life for patients affected by these interconnected conditions.
慢性肾脏病(CKD)与死亡率显著升高相关,主要原因是心血管疾病(CVD),这凸显了这两种疾病之间复杂的双向关系。尽管传统危险因素得到了控制,但仍会发生危及生命的心血管事件,这强调了非传统危险因素的潜在作用。CKD由于排泄废物的能力受损,导致矿物质失衡和尿毒症毒素蓄积,给心血管系统带来额外压力。而矿物质和尿毒症毒素的潴留反过来又会加重CKD的进展。本综述旨在阐明CKD与CVD之间的病理生理联系,特别关注钙和磷等矿物质以及尿毒症毒素所影响的代谢调节机制。我们回顾了这些因素如何通过炎症、内皮功能障碍、氧化应激和血管钙化等机制导致多器官损害加速。此外,我们还讨论了针对特定尿毒症毒素的治疗策略以及未来研究的方向。本综述深入探讨了CKD患者代谢失调与心血管结局之间的复杂相互作用,推动创新治疗干预措施的发展,最终改善受这些相互关联疾病影响患者的预后和生活质量。