Abstract: PUB093
Valproic Acid-Induced Nephrogenic Diabetes Insipidus: Unraveling a Rare Adverse Effect
Session Information
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Sahansra, Gurpreet, Northwell Health, New Hyde Park, New York, United States
- Yan, Christina, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, United States
- Bourdeau, Ariella, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, United States
- Chau, Matthew Kwun-Ting, Northwell Health, New Hyde Park, New York, United States
- Kraish, Ali, Northwell Health, New Hyde Park, New York, United States
- Maung, Erica, Northwell Health, New Hyde Park, New York, United States
- Shah, Nimesh K., Northwell Health, New Hyde Park, New York, United States
Introduction
Drug-induced nephrogenic diabetes insipidus (NDI) has been reported with chronic lithium exposure. However, valproic acid has rarely been implicated in renal tubular dysfunction, leading to subsequent NDI. We present a case of suspected valproic acid-induced NDI in a critically ill patient with persistent hypernatremia despite desmopressin administration.
Case Description
A 66-year-old male with chronic hypernatremia, chronic kidney disease, and schizoaffective disorder treated with long term valproic acid presented for septic shock secondary to community acquired pneumonia. Evaluation revealed hyperosmolar hypernatremia sodium of 165 mmol/L with inappropriately normal urine osmolarity of 24 mmol/L. Despite treatment with intravenous dextrose 5% in water and free-water flushes, serum sodium levels remained elevated at 161 mmol/L without an increase in urine osmolality. Desmopressin administration 2mcg failed to produce a urinary concentrating response. Copeptin level was elevated at 51.0pmol/L, supporting a diagnosis of NDI. The patient was treated with hydrochlorothiazide, while valproic acid was continued due to concern for the patient’s psychiatric stability.
Discussion
Diagnosing diabetes insipidus in critically ill patients can be challenging, particularly in the setting of sepsis, acute kidney injury, and exposure to nephrotoxic medications. In this patient, persistent hypernatremia with inappropriately dilute urine despite desmopressin exposure and elevated copeptin levels supported a diagnosis of NDI. While lithium remains the most recognized cause of drug-induced NDI, only one prior published case described an association between valproic acid and nephrogenic diabetes insipidus. In the absence of other known conditions and nephrotoxic agents, long-term valproic acid use was deemed the most likely contributor. This case highlights the importance of recognizing valproic acid as a rare but potential cause of NDI and underscores the dilemma in balancing psychiatric stability against possible systemic adverse effects.
Figure 1: Trends in: Serum Sodium, Urine Sodium, Urine osmol, and Urine Output
| Days Since Admission | Admission | 1 Day | 2 Days | 9 Days | 10 Days | 12 Days | 21 Days |
| Serum Na (mmol/L) | 165 | 158 | 143 | 161 | 154 | 158 | 144 |
| Urine Na (mmol/L) | 24 | -- | -- | 31 | 36 | 28 | -- |
| Urine Osmolality (mOsm/kgH2O) | 435 | -- | -- | 331 | 292 | 429 | -- |
| Urine Output (mL) | 2,790 | 1,019 | 2,710 | 3,265 | 1,000 | 2,320 | 2,700 |