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Introduction: Hyponatremia is a common cause of hospital and ICU admissions. Correcting sodium levels should be done gradually to avoid complications like osmotic demyelination syndrome. Desmopressin can be used to prevent rapid sodium fluctuations. While effective, limited evidence exists regarding its use in patients with renal dysfunction and package inserts recommend avoiding use in patients with creatinine clearance (CrCl) < 50mL/min. The purpose of this study was to determine if desmopressin was safe and effective in patients with renal dysfunction compared to those without. Methods: This retrospective cohort study was conducted at a single academic medical center. Adult patients with an initial sodium of < 125 mmol/L who received desmopressin were included. The primary outcome was the rate of sodium overcorrection (>8 mmol/L) 24 hours after desmopressin in patients with renal dysfunction (CrCl < 50 mL/min) versus those without. Secondary outcomes included proportion achieving a 5–10 mEq/L increase within 24 hours and overcorrection rates at 24 and 48 hours. Data were analyzed using chi-squared, t-test, and Mann-Whitney U tests. Results: 72 total patients were included with 20 having renal dysfunction. A rescue dosing strategy was used most commonly in both groups. Baseline sodium was comparable between groups (mmoL/L): 113.8 ± 7.5 vs. 115.6 ± 3.73; however, sodium prior to DDAVP was more elevated in the renal dysfunction group (mmol/L): 124.1 ± 9.8 vs. 129.3 ± 7.8 (p=0.04). Patients with renal dysfunction received significantly more sodium through IV fluids compared to those without (284.2 vs 90.7 mEq, p=0.001). There was no significant difference in the primary outcome of sodium overcorrection by >8mmol/L (8.2% vs 9.7%, p=0.14). Overcorrection rates at 24 and 48 hours were also similar (9.8% vs 28.6%, p=0.17 and 5.8% vs 15%, p=0.43). Conclusions: This study was the first of its kind to assess desmopressin efficacy and safety in the setting of renal dysfunction and did not show a significant difference in sodium overcorrection after desmopressin in those with renal dysfunction. Further studies assessing the impact of renal dysfunction on desmopressin safety and efficacy are needed.