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 vasopressin 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); no improvement in concentrating ability

Congenital arginine vasopressin resistance — formerly nephrogenic diabetes insipidus — caused by AVPR2 variants leads to very large urine volumes. Laboratory work suggested fluconazole might enhance aquaporin-2 water transport.

In this open-label study, five adult men with AVPR2-related disease took fluconazole 400 mg daily for 14 days. Median 24-hour urine output changed by +0.8 litres (range −3.6 to +5.7), and urine osmolality by −3 mOsm/kg. Responses to water deprivation did not change meaningfully.

Repurposing fluconazole for this condition is not supported. Management remains adequate water access, a low-solute diet and thiazides with or without NSAIDs as established.

• Fluconazole did not improve urine concentration or output in AVPR2-related vasopressin resistance.
• Continue standard management: free water access, low-solute diet and thiazides.
• Ensure patients have unrestricted access to water when admitted to hospital.
• Avoid fluid restriction protocols in these patients.

Why it matters

Drug repurposing hopes for this rare disorder have been raised by laboratory data, and this first clinical test was negative.

Don't overread it

Only five patients were studied for two weeks, so a small effect cannot be excluded.

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