Aletras Georgios, Bachlitzanaki Maria, Stratinaki Maria, Petrakis Ioannis, Georgopoulou Theodora, Pantazis Yannis, Foukarakis Emmanuel, Hamilos Michael, Stylianou Kostas
Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece.
School of Medicine, University of Crete, 70013 Heraklion, Greece.
J Clin Med. 2025 Jul 24;14(15):5230. doi: 10.3390/jcm14155230.
Chloride, long considered a passive extracellular anion, has emerged as a key determinant in the pathophysiology and management of heart failure (HF) and cardiorenal syndrome. In contrast to sodium, which primarily reflects water balance and vasopressin activity, chloride exerts broader effects on neurohormonal activation, acid-base regulation, renal tubular function, and diuretic responsiveness. Its interaction with With-no-Lysine (WNK) kinases and chloride-sensitive transporters underscores its pivotal role in electrolyte and volume homeostasis. Hypochloremia, frequently observed in HF patients treated with loop diuretics, is independently associated with adverse outcomes, diuretic resistance, and arrhythmic risk. Conversely, hyperchloremia-often iatrogenic-may contribute to renal vasoconstriction and hyperchloremic metabolic acidosis. Experimental data also implicate chloride dysregulation in myocardial electrical disturbances and an increased risk of sudden cardiac death. Despite mounting evidence of its clinical importance, serum chloride remains underappreciated in contemporary risk assessment models and treatment algorithms. This review synthesizes emerging evidence on chloride's role in HF, explores its diagnostic and therapeutic implications, and advocates for its integration into individualized care strategies. Future studies should aim to prospectively validate these associations, evaluate chloride-guided therapeutic interventions, and assess whether incorporating chloride into prognostic models can improve risk stratification and outcomes in patients with heart failure and cardiorenal syndrome.
长期以来，氯离子一直被视为一种被动的细胞外阴离子，如今已成为心力衰竭（HF）和心肾综合征病理生理学及管理中的关键决定因素。与主要反映水平衡和血管加压素活性的钠不同，氯离子对神经激素激活、酸碱调节、肾小管功能和利尿剂反应性具有更广泛的影响。它与无赖氨酸（WNK）激酶和氯敏感转运体的相互作用突出了其在电解质和容量稳态中的关键作用。在接受袢利尿剂治疗的HF患者中经常观察到的低氯血症与不良结局、利尿剂抵抗和心律失常风险独立相关。相反，高氯血症（通常是医源性的）可能导致肾血管收缩和高氯性代谢性酸中毒。实验数据还表明氯离子失调与心肌电紊乱和心脏性猝死风险增加有关。尽管有越来越多的证据表明其具有临床重要性，但血清氯离子在当代风险评估模型和治疗算法中仍未得到充分重视。本综述综合了关于氯离子在HF中作用的新证据，探讨了其诊断和治疗意义，并主张将其纳入个体化护理策略。未来的研究应旨在前瞻性地验证这些关联，评估以氯离子为导向的治疗干预措施，并评估将氯离子纳入预后模型是否可以改善心力衰竭和心肾综合征患者的风险分层及预后。
