Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115–2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457–3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299–2.545, p = 0.0005). Kaplan–Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients’ region of presentation suggests its general applicability across different ethnicities.
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