- Design
- Open-label, non-randomised clinical intervention study
- Population
- Five adult men with AVPR2-related congenital arginine vasopressin resistance
- Primary outcome
- 24-hour urine output and urinary concentrating ability
- Effect
- Median urine output change +0.8 L (range -3.6 to +5.7); urine osmolality -3 mOsm/kg; no concentrating improvement
Congenital arginine vasopressin resistance (formerly nephrogenic diabetes insipidus) causes massive urine output and dehydration risk, with no curative treatment. Preclinical work suggested the antifungal fluconazole could enhance aquaporin-2-mediated water transport, raising hope for repurposing.
In an open-label study, five adult men with AVPR2-related disease took fluconazole 400 mg daily for 14 days. The median change in 24-hour urine output was +0.8 litres (range -3.6 to +5.7), urine osmolality barely moved (-3 mOsm/kg), and concentrating ability on water deprivation did not improve.
This is a small, clean negative result: a mechanistically promising repurposing did not translate to patients. It is a useful corrective against off-label use on the strength of preclinical data, and a reminder that aquaporin-targeting for this disorder still lacks an effective option. The sample is tiny, but the direction is unambiguous.
- Fluconazole was tested in congenital arginine vasopressin resistance on preclinical promise.
- Urine output did not fall (median change +0.8 litres) over 14 days.
- Urine concentrating ability on water deprivation did not improve.
- Do not use fluconazole off-label for this disorder on preclinical grounds.
- An effective therapy for this condition is still lacking.
Why it matters
It stops a preclinically hyped repurposing before it reaches off-label practice in a desperate disease.
Don't overread it
Very small, open-label study; it argues against benefit but cannot formally exclude a small effect in subgroups.
The statistics, in plain English
With only five patients the study is tiny, but the complete absence of any reduction in urine output or osmolality makes a clinically useful effect very unlikely.
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