Serotonergic dysregulation: a path to early diagnosis of cardiorenal syndrome
Abstract
Cardiorenal syndrome remains one of the most complex and unresolved challenges in modern clinical medicine, associated with high mortality, frequent complications, and an unfavorable long-term prognosis for patients. Existing clinical guidelines do not solve the main problem: the biomarkers currently used in routine practice—serum creatinine, estimated glomerular filtration rate, and natriuretic peptides—respond to already established organ damage, predominantly of a single organ, or reflect systemic pathology as a whole, but they do not allow detection of preclinical shifts in inter-organ regulation at early stages. In this context, serotonin (5-hydroxytryptamine, 5-HT) is considered a promising integrative biomarker potentially capable of filling the existing diagnostic niche. To analyze current data on peripheral 5-HT metabolism, its active involvement in endothelial dysfunction, platelet-dependent inflammation, myocardial and renal tissue remodeling, and atherogenesis, 39 full-text publications (2000–2025) were selected from eLibrary.Ru and PubMed using the keywords “серотонин” (serotonin), “хроническая сердечная недостаточность” (chronic heart failure), and “хроническая болезнь почек” (chronic kidney disease). Special attention in this review is given to the phenomenon of opposite-directional changes in 5-HT levels in chronic heart failure and chronic kidney disease—an apparent contradiction that, on closer examination, becomes a potentially valuable diagnostic resource. Serotonin itself, its specific receptors, and major metabolites (5-HIAA, SERT, 5-HT1B/2A/2B/4 receptors) are discussed as candidates for the role of early markers of cardiorenal syndrome. At the same time, the current evidence base remains fragmentary: prospective studies assessing serotonin dynamics at different stages of cardiorenal syndrome are lacking, clinical reference intervals have not been defined, and the comparative informative value of plasma and platelet pools has not been investigated. Further validation of serotonin as a biomarker and study of the possibilities of pharmacological modulation of its receptors may open new approaches to early diagnosis and pathogenetic therapy of cardiorenal syndrome.