Noels Heidi, van der Vorst Emiel P C, Rubin Sébastien, Emmett Amber, Marx Nikolaus, Tomaszewski Maciej, Jankowski Joachim
Institute for Molecular Cardiovascular Research (H.N., E.P.C.v.d.V., J.J.), Uniklinik RWTH Aachen, RWTH Aachen University, Germany.
Aachen-Maastricht Institute for Cardiorenal Disease (H.N., E.P.C.v.d.V., J.J.), Uniklinik RWTH Aachen, RWTH Aachen University, Germany.
Circ Res. 2025 May 23;136(11):1306-1334. doi: 10.1161/CIRCRESAHA.124.325488. Epub 2025 May 22.
Chronic kidney disease (CKD) represents a global health issue with a high socioeconomic impact. Beyond a progressive decline of kidney function, patients with CKD are at increased risk of cardiovascular diseases, including heart failure (HF) and sudden cardiac death. HF in CKD can manifest both as HF with reduced ejection fraction and HF with preserved ejection fraction, with the latter further increasing in relative importance in the more advanced stages of CKD. Typical cardiac remodeling characteristics in uremic cardiomyopathy include left ventricular hypertrophy, myocardial fibrosis, cardiac electrical dysregulation, capillary rarefaction, and microvascular dysfunction, which are triggered by increased cardiac preload, cardiac afterload, and preload and afterload-independent factors. The pathophysiological mechanisms underlying cardiac remodeling in CKD are multifactorial and include neurohormonal activation (with increased activation of the renin-angiotensin-aldosterone system, the sympathetic nervous system, and mineralocorticoid receptor signaling), cardiac steroid activation, mitochondrial dysfunction, inflammation, innate immune activation, and oxidative stress. Furthermore, disturbances in cardiac metabolism and calcium homeostasis, macrovascular and microvascular dysfunction, increased cellular profibrotic responses, the accumulation of uremic retention solutes, and mineral and bone disorders also contribute to cardiovascular disease and HF in CKD. Here, we review the current knowledge of HF in CKD, including the clinical characteristics and pathophysiological mechanisms revealed in animal studies. We also elaborate on the detrimental impact of comorbidities of CKD on HF using hypertension as an example and discuss the clinical characteristics of hypertensive heart disease and the genetic predisposition. Overall, this review aims to increase the understanding of HF in CKD to support future research and clinical translational approaches for improved diagnosis and therapy of this vulnerable patient population.
慢性肾脏病（CKD）是一个具有高度社会经济影响的全球性健康问题。除了肾功能进行性下降外，CKD患者患心血管疾病的风险增加，包括心力衰竭（HF）和心源性猝死。CKD中的HF可表现为射血分数降低的HF和射血分数保留的HF，后者在CKD更晚期阶段的相对重要性进一步增加。尿毒症心肌病的典型心脏重塑特征包括左心室肥厚、心肌纤维化、心脏电调节异常、毛细血管稀疏和微血管功能障碍，这些是由心脏前负荷、心脏后负荷以及与前负荷和后负荷无关的因素增加所触发的。CKD中心脏重塑的病理生理机制是多因素的，包括神经激素激活（肾素 - 血管紧张素 - 醛固酮系统、交感神经系统和盐皮质激素受体信号激活增加）、心脏类固醇激活、线粒体功能障碍、炎症、固有免疫激活和氧化应激。此外，心脏代谢和钙稳态紊乱、大血管和微血管功能障碍、细胞促纤维化反应增加、尿毒症潴留溶质的积累以及矿物质和骨紊乱也促成了CKD中的心血管疾病和HF。在此，我们综述了当前关于CKD中HF的知识，包括动物研究中揭示的临床特征和病理生理机制。我们还以高血压为例阐述了CKD合并症对HF的有害影响，并讨论了高血压心脏病的临床特征和遗传易感性。总体而言，本综述旨在增进对CKD中HF的理解，以支持未来针对这一脆弱患者群体进行改善诊断和治疗的研究及临床转化方法。
