Sessa Concetto, Granata Antonio, Gaudio Agostino, Xourafa Anastasia, Malatino Lorenzo, Lentini Paolo, Fatuzzo Pasquale, Rapisarda Francesco, Castellino Pietro, Zanoli Luca
U.O.C Nefrologia e Dialisi, P.O. "Maggiore" di Modica, Ragusa.
U.O.C di Nefrologia, Azienda Ospedaliera per l'Emergenza "Cannizzaro" - Catania.
G Ital Nefrol. 2020 Feb 12;37(1):2020-vol1.
The Cardiorenal Syndrome type 4 (CRS-4) defines a pathological condition in which a primary chronic kidney disease (CKD) leads to a chronic impairment of cardiac function. The pathophysiology of CRS-4 and the role of arterial stiffness remain only in part understood. Several uremic toxins, such as uric acid, phosphates, advanced glycation end-products, asymmetric dimethylarginine, and endothelin-1, are also vascular toxins. Their effect on the arterial wall may be direct or mediated by chronic inflammation and oxidative stress. Uremic toxins lead to endothelial dysfunction, intima-media thickening and arterial stiffening. In patients with CRS-4, the increased aortic stiffness results in an increase of cardiac workload and left ventricular hypertrophy whereas the loss of elasticity results in decreased coronary artery perfusion pressure during diastole and increased risk of myocardial infarction. Since the reduction of arterial stiffness is associated with an increased survival in patients with CKD, the understanding of the mechanisms that lead to arterial stiffening in patients with CRS4 may be useful to select potential approaches to improve their outcome. In this review we aim at discussing current understanding of the pathways that link uremic toxins, arterial stiffening and impaired cardiac function in patients with CRS-4.
4型心肾综合征(CRS-4)定义了一种病理状态,即原发性慢性肾脏病(CKD)导致心脏功能的慢性损害。CRS-4的病理生理学以及动脉僵硬度的作用仅部分为人所知。几种尿毒症毒素,如尿酸、磷酸盐、晚期糖基化终产物、不对称二甲基精氨酸和内皮素-1,也是血管毒素。它们对动脉壁的作用可能是直接的,也可能是由慢性炎症和氧化应激介导的。尿毒症毒素会导致内皮功能障碍、内膜中层增厚和动脉僵硬。在CRS-4患者中,主动脉僵硬度增加会导致心脏工作负荷增加和左心室肥厚,而弹性丧失会导致舒张期冠状动脉灌注压降低和心肌梗死风险增加。由于降低动脉僵硬度与CKD患者生存率提高相关,了解导致CRS4患者动脉僵硬的机制可能有助于选择改善其预后的潜在方法。在本综述中,我们旨在讨论目前对CRS-4患者中连接尿毒症毒素、动脉僵硬和心脏功能受损的途径的理解。