Abstract: FR-PO0630
Utility of Acetazolamide in Lithium-Induced Arginine Vasopressin Resistance
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Lee, Jaeine, Boston Medical Center, Boston, Massachusetts, United States
- Menn-Josephy, Hanni, Boston Medical Center, Boston, Massachusetts, United States
Introduction
Arginine vasopressin resistance (AVR) is a well-known complication of lithium (Li) therapy. Mainstay treatment includes thiazide and amiloride, which reduce polyuria by inducing hypovolemia-mediated proximal sodium and water reabsorption, upregulating aquaporin-2 (AQP2), and limiting Li entry into principal cells of the collecting duct. However, thiazides can raise serum Li levels and cause multiple electrolyte derangements. Acetazolamide has shown benefit in animal and congenital models of AVR by reducing glomerular filtration rate via tubuloglomerular feedback and attenuating AQP2 downregulation, with potentially fewer adverse effects, but its clinical use in adult patients remains limited.
Case Description
A 63-year-old male with a history of anal squamous cell carcinoma and bipolar disorder on Li for over 20 years presented with dyspnea and was found to have gram-negative bacteremia due to pyelonephritis and malignant obstructive nephropathy. He presented with polyuria (7-8 L/day), serum sodium 150 mmol/L, urine osmolality 121 mOsm/kg H2O, and free water clearance 4.8 L/day. Thiazides were avoided due to severe hypomagnesemia (0.9 mg/dL), attributed to diarrhea and panitumumab, and concern for Li toxicity. Desmopressin and amiloride failed to improve polyuria, and the patient required intravenous (IV) dextrose water to maintain normonatremia for a week due to poor oral intake. Li was down-titrated due to the above significant challenges. Acetazolamide was introduced seven days after these interventions. Despite persistent polyuria (5-6 L/day), he maintained normonatremia off IV fluids for 1 day. Upon doubling the dose, urine output decreased to 3.6 L/day, normonatremia (141 mmol/L) was maintained, urine osmolality improved to 191 mOsm/kg H2O, and free water clearance decreased to 1.9 L/day.
Discussion
This case highlights acetazolamide as a viable alternative in Li-induced AVR when standard therapies are limited. Although current evidence is largely from animal and congenital models, this case demonstrates successful use in an adult, allowing rapid IV fluid weaning and potentially shortening hospitalization. Acetazolamide may also offer a reduced risk of Li toxicity as it inhibits renal tubular reabsorption of Li, and fewer electrolyte disturbances compared to thiazide-based therapy, suggesting its potential for broader use in difficult-to-manage Li-induced AVR.