Chronic kidney disease (CKD) affects millions of people globally and, for most patients, the risk of developing cardiovascular disease is higher than that of progression to kidney failure. Moreover, mortality owing to cardiovascular complications in patients with CKD is markedly higher than in matched individuals from the general population. This mortality was traditionally thought to be driven by coronary heart disease but >75% of patients with CKD have left ventricular hypertrophy, which contributes to mortality, particularly sudden cardiac death. The aetiology of cardiac complications in CKD is multifactorial. In addition to haemodynamic overload, uraemic toxin accumulation and altered ion homeostasis, which are known to underlie left ventricular hypertrophy in CKD and drive cardiac dysfunction, we examine the role of myocardial metabolic remodelling in CKD. Uraemic cardiomyopathy is characterized by myriad cardiac metabolic maladaptations, including altered mitochondrial function, changes in myocardial substrate utilization, altered metabolic transporter function and expression, and impaired insulin response and phosphoinositide-3 kinase–AKT signalling, which collectively lead to impaired cardiac energetics. Interestingly, none of the standard treatments used to treat CKD target the metabolism of the uraemic heart directly. An improved understanding of the cardiac metabolic perturbations that occur in CKD might allow the development of novel treatments for uraemic cardiomyopathy.

慢性肾脏病 (CKD) 影响着全球数百万人，对于大多数患者而言，患心血管疾病的风险高于进展为肾衰竭的风险。此外，CKD 患者因心血管并发症导致的死亡率明显高于一般人群中匹配的个体。这种死亡率传统上被认为是由冠心病引起的，但 >75% 的 CKD 患者有左心室肥大，这会导致死亡率，尤其是心源性猝死。CKD 心脏并发症的病因是多因素的。除了血液动力学超负荷、尿毒症毒素积累和改变的离子稳态外，已知这些是 CKD 左心室肥大和驱动心功能障碍的基础，我们检查了心肌代谢重塑在 CKD 中的作用。尿毒症心肌病的特征是多种心脏代谢适应不良，包括线粒体功能改变、心肌底物利用改变、代谢转运蛋白功能和表达改变以及胰岛素反应和磷酸肌醇 3 激酶-AKT 信号传导受损，这些共同导致心脏能量受损。有趣的是，用于治疗 CKD 的标准疗法都没有直接针对尿毒症心脏的新陈代谢。更好地了解 CKD 中发生的心脏代谢紊乱可能有助于开发尿毒症心肌病的新疗法。心肌底物利用的变化、代谢转运蛋白功能和表达的改变以及胰岛素反应和磷酸肌醇 3 激酶-AKT 信号传导受损，这些共同导致心脏能量受损。有趣的是，用于治疗 CKD 的标准疗法都没有直接针对尿毒症心脏的新陈代谢。更好地了解 CKD 中发生的心脏代谢紊乱可能有助于开发尿毒症心肌病的新疗法。心肌底物利用的变化、代谢转运蛋白功能和表达的改变以及胰岛素反应和磷酸肌醇 3 激酶-AKT 信号传导受损，这些共同导致心脏能量受损。有趣的是，用于治疗 CKD 的标准疗法都没有直接针对尿毒症心脏的新陈代谢。更好地了解 CKD 中发生的心脏代谢紊乱可能有助于开发尿毒症心肌病的新疗法。