SUN-008 A Case of Severe Polyuria: Diagnostic Challenges and Management of Nephrogenic Diabetes Insipidus

Abstract Disclosure: A. Rios Chen: None. I. Kasimoglu: None. Background: Arginine vasopressin V2 resistance (AVP-R), commonly known as nephrogenic diabetes insipidus (NDI), is an uncommon disorder in which the kidneys fail to respond to AVP, causing significant polyuria. NDI can be hereditary (X-linked or autosomal) or acquired from medications or systemic conditions (1). Clinical Case: A 40-year-old man with hypertension was admitted for community-acquired pneumonia. He had urinary output of 11-14 liters with intake of 2.8-5.3 liters/day. Laboratory results revealed a normal serum sodium (142 mmol/L), normal serum osmolality (291 mOsm/kg), and low urinary osmolality (64 mOsm/kg). He mentioned a possible diagnosis of NDI in infancy and noted that his older brother had confirmed NDI, suggesting a hereditary component. Although he had been prescribed hydrochlorothiazide in the past, he was not adherent and did not have consistent follow up. Evaluation confirmed marked polyuria with abnormally low urine osmolality. To determine the underlying cause of water diuresis, a desmopressin challenge was performed. The administration of desmopressin (2 mcg IV) revealed very minimal urine osmolality increases: 71 at 30 minutes, 81 at 1 hour, 75 at 1.5 hours, and 58 at 2 hours. Urine osmolality remained below 300 mOsm/kg, with an increase of less than 45%, confirming AVP-R. The minimal osmolality increase (<15% at 1 hour, negligible at 2 hours) indicated complete AVP-R. Treatment with hydrochlorothiazide (50 mg daily), amiloride (5 mg daily), and a low-salt, low-protein diet decreased urinary output to about 5 liters per day. The patient was discharged with instructions for endocrinology follow-up and genetic testing. Conclusion: Hereditary AVP-R, as seen in this patient, is a rare condition characterized by varying degrees of resistance to AVP. Approximately 90% of hereditary cases are linked to X-linked AVPR2 mutations (2,3), underscoring the importance of genetic testing. This case shows the difficulties in distinguishing AVP-R (NDI) from other causes of polyuria and demonstrates the pivotal role of desmopressin testing in confirming the diagnosis. The patient’s substantial improvement with hydrochlorothiazide and amiloride highlights the effectiveness of tailored therapy. Early detection, consistent treatment adherence, and long-term follow-up are crucial for achieving optimal clinical outcomes. References: 1. Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015;11(10):576-88. 2. Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005;16(10):2836-46. 3. Bichet DG. Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin Nephrol. 2008;28(3):245-51. Keywords: Nephrogenic Diabetes Insipidus (NDI), Arginine Vasopressin V2 resistance (AVP-R) Presentation: Sunday, July 13, 2025