Myocardial adaptations in advanced kidney disease. Myocardial adaptations in advanced kidney disease

Molecular changes underlying the failing heart in chronic kidney disease (CKD) remains largely undefined. To date, a severe paucity of translational studies investigating these changes utilizing human heart tissues from kidney failure patients exists. Moreover, no studies have examined alterations of the cardiac cytoskeleton in CKD, despite its central role in regulating organelle function, bioenergetics and myocardial remodeling. In this 3-arm cross-sectional controlled cohort study, we compared donor heart tissues from dialysis patients, to patients with hypertension with relatively preserved GFR, and healthy controls. We present evidence for transcriptomic changes in the hearts of dialysis patients, involving cytoskeletal dysregulation and dysfunction of mitochondrial bioenergetics. Overall design: We conducted a 3-arm observational cross-sectional controlled cohort study of explanted human heart tissues. 109 donor hearts were collected, 50 met eligibility criteria for inclusion from hemodialysis-dependent patients (HD), hypertension (HTN) with relatively preserved GFR and healthy controls. Left ventricular tissues were subjected to pathologic examination and RNA-sequencing.

慢性肾脏病（chronic kidney disease, CKD）患者衰竭心脏的分子机制迄今尚未完全阐明。迄今为止，利用肾衰竭患者的人类心脏组织开展此类分子变化相关转化研究的报道仍极为匮乏。此外，尽管心脏细胞骨架在调控细胞器功能、生物能代谢与心肌重构中发挥核心作用，但目前尚无针对慢性肾脏病中心脏细胞骨架改变的相关研究。本研究为一项三臂观察性横断面对照队列研究，将透析患者的供体心脏组织与肾小球滤过率（glomerular filtration rate, GFR）相对保留的高血压患者及健康对照者的供体心脏组织进行了对比分析。本研究揭示了透析患者心脏中的转录组学改变，其涉及细胞骨架失调与线粒体生物能代谢功能异常。
研究设计：我们针对离体获取的人类心脏组织开展了一项三臂观察性横断面对照队列研究。本研究共收集109例供体心脏，其中50例符合纳入标准，分别纳入依赖血液透析（hemodialysis, HD）的患者组、肾小球滤过率相对保留的高血压患者（hypertension, HTN）组以及健康对照者组。对所有入选样本的左心室组织进行了病理学检查与RNA测序（RNA-sequencing）。