- Design
- Open-label, non-randomised intervention study
- Population
- 5 adult men with AVPR2-related congenital vasopressin resistance
- Primary outcome
- 24-hour urine output and urine concentrating ability
- Effect
- Median urine output +0.8 L (−3.6 to +5.7); urine osmolality −3 mOsm/kg
Arginine vasopressin resistance, formerly nephrogenic diabetes insipidus, can produce more than 10 litres of urine a day and has no curative treatment. Laboratory work suggested fluconazole might enhance aquaporin-2 water transport. This open-label, non-randomised study gave five adult men with AVPR2-related disease fluconazole 400 mg daily for 14 days.
Despite adequate drug levels, median 24-hour urine output changed by +0.8 L (range −3.6 to +5.7) and urine osmolality by −3 mOsm/kg, with no change in voiding frequency. A water deprivation test showed no improvement in concentrating ability.
Five patients is a very small study, but the result is consistently null. Standard management — free access to water, a low-solute diet, and thiazides with or without amiloride or NSAIDs — remains the approach.
- Fluconazole is not an effective treatment for inherited vasopressin resistance on current evidence.
- Ensure patients with vasopressin resistance have unrestricted access to water, especially when unwell or fasting.
- Thiazides, a low-solute diet and sometimes NSAIDs or amiloride remain the mainstays of treatment.
- Flag the diagnosis prominently so that fluids are not restricted during admissions.
Why it matters
A promising repurposing idea did not translate into patients.
Don't overread it
Five patients cannot exclude a small effect or benefit in other genetic forms of the condition.
The statistics, in plain English
With five patients and no control group, the study can only show a lack of large effect. The wide ranges in urine output reflect the day-to-day variability of the condition.
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