THERAPEUTIC APPROACH TO HYPONATREMIA WITH ORAL UREA: BEYOND FLUID RESTRICTION. CASE SERIES FROM A MEDIUM-SIZED HOSPITAL IN SPAIN

According to various studies, the prevalence of hyponatremia range from 27% to 58% in congestive heart failure, up to 49% in cirrhosis, and 28% in pulmonary infections (1). An analysis of hospitalized and non-hospitalized individuals in a Spanish hospital found that hyponatremia occurs in about 9% of sodium measurements in both hospital and general population settings (2). Hyponatremia is associated with cognitive deficits, gait disturbances, falls, bone fractures (3), mortality (4), and has a significant clinical and economic burden (5). In patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), recent guidelines recommend, as a second-line treatment, increasing solute intake with 0.25-0.50 g/kg per day of urea, after fluid restriction with the same level of evidence (2D) (6). Evidence from randomized clinical trials regarding the treatment of chronic hyponatremia is limited (7). Here, we present a case series from the registry of hyponatremia treated with oral urea from a medium-sized hospital in Spain, aiming to explore its effectiveness and safety in patients with hyponatremia due to SIADH and other causes.

We conducted a cross-sectional retrospective observational study, involving adult diagnosed with hyponatremia for any reason and receiving chronic treatment with oral urea at the Hospital General Universitario Nuestra Señora del Prado (HGUNSP) in Talavera de la Reina, Spain, from January 2018 to October 2023. Data were extracted from electronic medical records. Urea treatment was prescribed by physicians from various specialties, including nephrology, internal medicine, oncology, hematology, neurology, cardiology, and gastroenterology. The analysis of categorical variables was performed using percentages and mean with standard deviation (SD) for quantitative variables. Normality of the sample distribution was assessed through the Kolmogorov-Smirnov test. Hypothesis testing was conducted using the chi-square, Wilcoxon, and Friedman tests. Survival analysis was used to evaluate the time to normonatremia. Statistical significance was set at P<0.05. The statistical analysis was performed using the SPSS v.23 software package.

We identified a total of 23 individuals (62.2% males) with an average age of 67.96 ± 15.34 years. The most prevalent etiology of hyponatremia was neoplasms (47.8%), followed by antiepileptic drugs (17.4%). Up to 82.6% of the patients met SIADH criteria. Also, urea treatment was used in hypervolemic patients (heart failure) and hyponatremia due to alcoholism (table 1). In the usual treatment of patients, drugs that could potentially induce hyponatremia were found, including diuretics (30.4%), proton pump inhibitors (78.3%), and antiepileptic drugs (52.2%). Whereas the sample showed normal distribution, non-parametric test were used due to small sample size (N<30). The average urea dose at the beginning of the treatment was 16.4 ± 4.3. Serum sodium was 122 ± 4.5 vs. 136.35 ± 3.9 with oral urea (P<0.05) (figure 1). The change in serum urea was 37.5 ± 25.8 (baseline) to 74.4 ± 28.2 (P<0.05) at six months (figure 2), with serum osmolarity increasing to 255.4 ± 122.3 (P>0.05). At six months of treatment, hyponatremia was corrected in all treated patients. The time from the start of treatment to normonatremia was 4.5 [95% CI 3.5-5.4] months (figure 3). Side effects were observed in 2 patients (8.7%), while 91.3% remained asymptomatic (P<0.05). In one case, asymptomatic transient hypernatremia was observed, while in another case, the patient discontinued treatment due to intractable gastrointestinal symptoms (constipation) (table 2).