Background and Objectives: Differentiating between hypovolemic (HH) and euvolemic hyponatremia (EH) is crucial for correct diagnosis and therapy, but can be a challenge. We aim to ascertain whether changes in serum creatinine (SC) can be helpful in distinguishing HH from EH. Materials and Methods: Retrospective analysis of patients followed in a monographic hyponatremia outpatient clinic of a tertiary hospital during 1 January 2014–30 November 2019. SC changes during HH and EH from eunatremia were studied. The diagnostic accuracy of the SC change from eunatremia to hyponatremia (∆SC) was analyzed. Results: A total of 122 hyponatremic patients, median age 79 years (70–85), 46.7% women. In total, 70/122 patients had EH, 52/122 HH. During hyponatremia, median SC levels increased in the HH group: +0.18 mg/dL [0.09–0.39, p < 0.001], but decreased in the EH group: −0.07 mg/dL (−0.15–0.02, p < 0.001), as compared to SC in eunatremia. HH subjects presented a higher rate of a positive ∆SC than EH (90.4% vs. 25.7%, p < 0.001). EH subjects presented a higher rate of a negative/null ∆SC than HH (74.3% vs. 9.6%, p < 0.001). ROC curve analysis found an AUC of 0.908 (95%CI: 0.853 to 0.962, p < 0.001) for ∆SC%. A ∆SC% ≥ 10% had an OR of 29.0 (95%CI: 10.3 to 81.7, p < 0.001) for HH. A ∆SC% ≤ 3% had an OR of 68.3 (95%CI: 13.0 to 262.2, p < 0.001) for EH. Conclusions: The assessment of SC changes from eunatremia to hyponatremia can be useful in distinguishing between HH and EH.

We evaluated the hospital evolution of hyponatremia and inflammation markers in patients with coronavirus disease 2019 (COVID-19). The hospital evolutions of a cohort of adult patients with COVID-19 pneumonia and hyponatremia were retrospectively analyzed. Data of the admission day, 2nd–3rd and 7th–10th day of hospitalization, and of the discharge day were collected. Comparative and multivariate analyzes were developed, and Hazzard ratio (HR) with 95% confidence intervals (95% CI) were calculated. Of the 172 hospitalized patients with COVID-19, 49 of them (28.5%) had hyponatremia, which were analyzed. A total of 32/49 (65.3%) patients were male, and 22/49 (44.9%) euvolemic. Mean age: 69.9 ± 14.7 years. All patients had high inflammatory markers at admission. Of the total patients with hyponatremia at admission, only 26.2% remained hyponatremic at the 7th–10th day of hospitalization. Improvement in serum sodium (SNa) coincided with improvement in inflammatory markers during hospitalization, in both euvolemic and hypovolemic hyponatremic patients. A higher serum creatinine at admission was independently associated with mortality (HR: 12.23, 95% CI: 2 to 25.6) in hyponatremic COVID-19 patients. In conclusion, both hypovolemic and euvolemic hyponatremia in COVID-19 patients occurred in an inflammation status, and improved as inflammation decreased.