CYCLOPHOSPHAMIDE-INDUCED HYPONATREMIA: EPIDEMIOLOGY, PATHOPHYSIOLOGY, DIAGNOSTICS AND TREATMENT (A NARRATIVE REVIEW)

DOI: 10.22138/2500-0918-2026-23-1-112-133

D.A. Oberiukhtin¹, A.P. Sarapultsev¹, A.E. Chernitskiy²

¹Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russian Federation;
²Ural Federal Agrarian Research Center of the Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russian Federation

Abstract. Background: Cyclophosphamide (CP) is a widely used alkylating agent in oncology and immunology; however, its administration may be complicated by hyponatremia, a potentially serious disorder of water–electrolyte balance. Objective: To synthesize current evidence on the epidemiology, pathophysiological mechanisms, diagnostic approach, and management of CP-induced hyponatremia. Materials and Methods: A narrative review of the recent literature was conducted, integrating data from retrospective and prospective clinical studies, experimental models, and mechanistic investigations relevant to CP-associated hyponatremia. Results: Available clinical evidence indicates that hyponatremia may occur across a wide range of CP doses and clinical populations, with higher incidence reported at increased cumulative doses and in the presence of identifiable risk factors, including female sex, low baseline serum sodium, renal dysfunction, and concomitant administration of hypotonic fluids. The pathophysiology appears heterogeneous and may involve both central and renal mechanisms of impaired water excretion. These include vasopressin-mediated antidiuresis consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH), as well as a nephrogenic component of inappropriate antidiuresis (NSIAD-like mechanism), in which CP metabolites promote V2-receptor–dependent aquaporin-2 upregulation and enhanced renal free-water reabsorption. The coexistence of these mechanisms may contribute to interindividual variability in clinical presentation and the rapid development of dilutional hyponatremia following CP administration. Diagnosis is based on confirmation of hypotonic euvolemic hyponatremia and systematic exclusion of alternative etiologies. Conclusions: Management of CP-induced hyponatremia requires balancing the need for hydration to prevent hemorrhagic cystitis against the risk of exacerbating water retention. Current data support consideration of isotonic hydration strategies and, in selected cases, vasopressin V2-receptor antagonists with careful monitoring of sodium correction. Further prospective studies are needed to clarify individual susceptibility factors and to refine preventive and therapeutic approaches within this mechanistic framework

Keywords: cyclophosphamide, hyponatremia, SIADH, vasopressin V2 receptor, aquaporin-2, vaptans, cancer chemotherapy

The authors declare no conflict of interest.
Corresponding author:
Alexey P. Sarapultsev
a.sarapultsev@gmail.com
Received: 22.12.2025
For citation: Oberiukhtin D.A., Sarapultsev A.P., Chernitskiy A.E. Cyclophosphamide-induced hyponatremia: epidemiology, pathophysiology, diagnostics and treatment (a narrative review) [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2026, Vol. 23, no. 1, pp. 112–133. DOI: 10.22138/2500-0918-2026-23-1-112-133 (In Russ)

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Authors
Denis A. Oberiukhtin
Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences
Postgraduate Student
oberuhtindenis@gmail.com
ORCID ID: 0009-0006-1497-5740
eLibrary SPIN: 6105-8636
Yekaterinburg, Russian Federation

Alexey P. Sarapultsev
Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences
Doctor of Sciences (Biology), Head of the Laboratory of Immunopathophysiology
asarapultsev@gmail.com
ORCID ID: 0000-0003-3101-9655
eLibrary SPIN: 7212-5394
Yekaterinburg, Russian Federation

Anton E. Chernitskiy
Ural Federal Agrarian Research Center of the Ural Branch of the Russian Academy of Sciences
Doctor of Sciences (Biology), Chief scientific secretary, Leading researcher of Department of Reproductive Biology and Neonatology
ORCID ID: 0000-0001-8953-687X
eLibrary SPIN: 3776-3502
Yekaterinburg, Russian Federation