{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:37:11Z","timestamp":1791221831567,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"medical scientific society \u201cEMEKNNOK\u201d","award":["17\/31122024"],"award-info":[{"award-number":["17\/31122024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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\u2013base 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\u2014often iatrogenic\u2014may 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/jcm14155230","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T09:05:12Z","timestamp":1753347912000},"page":"5230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Role of Chloride in Cardiorenal Syndrome: A Practical Review"],"prefix":"10.3390","volume":"14","author":[{"given":"Georgios","family":"Aletras","sequence":"first","affiliation":[{"name":"Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"},{"name":"School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bachlitzanaki","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 70013 Heraklion, Greece"},{"name":"Second Department of Internal Medicine, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8720-1830","authenticated-orcid":false,"given":"Maria","family":"Stratinaki","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-9823","authenticated-orcid":false,"given":"Ioannis","family":"Petrakis","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 70013 Heraklion, Greece"},{"name":"Department of Nephrology, University General Hospital of Heraklion, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Georgopoulou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"},{"name":"School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannis","family":"Pantazis","sequence":"additional","affiliation":[{"name":"Institution of Applied and Computational Mathematics, Foundation of Research and Technology-Hellas, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1340-2282","authenticated-orcid":false,"given":"Emmanuel","family":"Foukarakis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hamilos","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 70013 Heraklion, Greece"},{"name":"Department of Cardiology, University General Hospital of Heraklion, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3678-9421","authenticated-orcid":false,"given":"Kostas","family":"Stylianou","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 70013 Heraklion, Greece"},{"name":"Department of Nephrology, University General Hospital of Heraklion, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e840","DOI":"10.1161\/CIR.0000000000000664","article-title":"Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement from the American Heart Association","volume":"139","author":"Rangaswami","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dutta, A., Saha, S., Bahl, A., Mittal, A., and Basak, T. 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