Predictions of Cisplatin-induced Hyponatremia in patients with malignancy: A retrospective cohort survey of all cisplatin administration in clinical practice

Background: Despite the rise of cancer immunotherapy, cisplatin remains a cornerstone in chemotherapy. Hyponatremia is a common but under-recognized adverse event of cisplatin. Previous studies on cisplatin-induced hyponatremia (CIH) are limited and mostly focus on the initial administration. This study aimed to assess the overall incidence of CIH and identify significant predictive factors. Methods: We conducted a single-center, retrospective cohort study of patients who received intravenous cisplatin at Juntendo University Hospital between 2018 and 2020. The occurrence and severity of CIH were assessed across all administrations. Predictive factors were analyzed using multiple linear regression and linear mixed-effects models. Results: Among 706 patients, 340 (48.2%) experienced CIH during the study period, with 103 (14.6%) developing Grade 3 or higher severity. Across 1,939 total cisplatin administrations, CIH occurred in 585 (30.2%) cases, including 135 (7.0%) with Grade ≥3 severity. CIH was most common at first administration (38.8%), with severe cases occurring in 11.9%. Linear Mixed Effects Model results that the significant prognostic factors for cisplatin-induced Hyponatremia were age (OR: 1.41, p = 0.00), last cisplatin dose (OR: 1.74, p = 0.00), serum albumin (OR: 0.65, p = 0.00), serum sodium (OR: 0.35, p = 0.00), WBC (OR: 1.26, 9p = 0.01), and concomitant 5FU administration (OR: 3.91, 9p = 0.00). Conclusions: CIH is a frequent and potentially serious complication of cisplatin therapy. Older age, high-dose cisplatin, hypoalbuminemia, hyponatremia, leukocytosis, and 5-FU co-administration significantly increase the risk. These findings highlight the importance of proactive monitoring and management strategies to mitigate CIH risk.