Fluconazole did not reduce urine output in congenital vasopressin resistance

Design

Open-label, non-randomised intervention study

Population

5 adult men with AVPR2-related congenital AVP resistance

Primary outcome

24-hour urine output and urine concentrating ability

Effect

Median urine output change +0.8 L (range −3.6 to +5.7); osmolality −3 mOsm/kg

Congenital arginine vasopressin resistance — previously nephrogenic diabetes insipidus — caused by AVPR2 variants can produce more than 10 litres of urine a day. Preclinical work suggested fluconazole might enhance aquaporin-2 water transport. This open-label, non-randomised study gave five adult men fluconazole 400 mg daily for 14 days.

Urine output did not fall (median change +0.8 L, range −3.6 to +5.7), urine osmolality was unchanged (−3 mOsm/kg) and micturition frequency did not change. Water deprivation responses were similar before and after.

The study is tiny, but it answers the practical question for now: fluconazole should not be used off-label for this condition. Thiazides, low solute intake and free access to water remain the mainstay.

• Do not use fluconazole off-label for congenital vasopressin resistance.
• Continue standard care: free water access, low-salt and low-protein diet, and thiazide diuretics with or without NSAIDs.
• Use the new term 'arginine vasopressin resistance' alongside nephrogenic diabetes insipidus in letters for clarity.
• Plan fluid access carefully around surgery, fasting and illness in these patients.

Why it matters

It closes a repurposing idea that had moved from the laboratory into patient forums.

Don't overread it

Five patients over two weeks, open-label; it cannot exclude a small effect or benefit in other variants.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.