Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) offer a novel approach to cancer treatment by enhancing immune responses against malignant cells. However, ICIs are associated with immune-related adverse events (irAEs), including hyponatremia, a potentially severe electrolyte disturbance. The risk of hyponatremia increases further when ICIs are combined with cisplatin, a nephrotoxic chemotherapy agent widely used in treating respiratory and intrathoracic cancers. This study investigated the incidence, severity, and temporal dynamics of hyponatremia in patients treated with ICIs alone or in combination with cisplatin. METHODS: A retrospective cohort study was conducted using data from the TriNetX global health research network. Patients with respiratory or intrathoracic malignancies (n = 14,026) were divided into two groups: ICI-only (n = 7013) and ICI with cisplatin combination (n = 7013), matched using propensity scores. Hyponatremia was categorized into mild (130-134 mmol/L), moderate (125-129 mmol/L), and severe (<125 mmol/L). Temporal trends and cumulative incidence over 90 days were analyzed using Poisson regression. RESULTS: The combination group exhibited a higher cumulative incidence of hyponatremia across all severity levels, with early-phase risk peaking within 20 days of treatment. Rate ratios for mild, moderate, and severe hyponatremia were significantly elevated in the combination group (p < 0.01). CONCLUSIONS: Hyponatremia is a significant complication in patients receiving ICIs, particularly when combined with cisplatin. Early monitoring and tailored management are essential to mitigate risks and optimize treatment outcomes.