Kidney international · 2026
Impact of fluconazole in vasopressin 2 receptor-related congenital arginine vasopressin resistance.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Mortensen Line A, Bistrup Claus, Rittig Søren, Hertz Jens Michael, Schmidt-Ott Kai M, Klussman Enno, Hinze Christian, Jensen Boye L, Hinrichs Gitte R
Аннотация
INTRODUCTION: Arginine vasopressin resistance (AVP-R), previously called nephrogenic diabetes insipidus is a rare inherited disorder characterized by excessive urine output (often over 10 l/d) and a risk of life-threatening dehydration, resulting from kidney collecting duct insensitivity to arginine vasopressin. Currently, no curative treatment exists. Preclinical studies suggest that repurposing of anti-fungal fluconazole enhances AQP2-mediated water transport. Here, we present results from a clinical intervention study evaluating the effect of fluconazole on 24-hour urine output and urine concentrating ability in patients with congenital AVP-R caused by a pathogenic variant in the AVPR2 gene encoding the receptor of AVP.
METHODS: We performed an open-label, non-randomized intervention in five adult males with AVPR2-related AVP-R. Participants received oral fluconazole 400 mg daily for 14 days, with baseline and follow-up assessments including water deprivation test. The primary endpoints were 24-hour urine output and urinary concentrating ability. Secondary endpoints included urinary and plasma osmolality, surrogate copeptin secretion, electrolytes, and micturition frequency. Safety and treatment adherence were evaluated weekly.
RESULTS: Median fluconazole concentration following treatment were 13.7 μg/ml (range 12.1-24.4) in plasma and 28.6 μg/ml (range 22.4-34.7) in urine, respectively. Median change in 24-h urine output was +0.8 l (range -3.6 to +5.7) and in urine osmolality -3 mOsm/kg (range -78 to +25), with no change in micturition frequency. During water deprivation, body weight decreased -2.0 to -2.8 kg at baseline vs. -2.1 to -3.1 kg after treatment, urine osmolality changed -91 to +222 vs. -12 to +193 mOsm/kg, and plasma copeptin increased 4.8 to 16.8 vs. 4.2 to 12.9 pmol/l.
CONCLUSIONS: Fluconazole treatment did not reduce urine output or improve urine concentrating ability in adult patients with congenital AVP-R.
METHODS: We performed an open-label, non-randomized intervention in five adult males with AVPR2-related AVP-R. Participants received oral fluconazole 400 mg daily for 14 days, with baseline and follow-up assessments including water deprivation test. The primary endpoints were 24-hour urine output and urinary concentrating ability. Secondary endpoints included urinary and plasma osmolality, surrogate copeptin secretion, electrolytes, and micturition frequency. Safety and treatment adherence were evaluated weekly.
RESULTS: Median fluconazole concentration following treatment were 13.7 μg/ml (range 12.1-24.4) in plasma and 28.6 μg/ml (range 22.4-34.7) in urine, respectively. Median change in 24-h urine output was +0.8 l (range -3.6 to +5.7) and in urine osmolality -3 mOsm/kg (range -78 to +25), with no change in micturition frequency. During water deprivation, body weight decreased -2.0 to -2.8 kg at baseline vs. -2.1 to -3.1 kg after treatment, urine osmolality changed -91 to +222 vs. -12 to +193 mOsm/kg, and plasma copeptin increased 4.8 to 16.8 vs. 4.2 to 12.9 pmol/l.
CONCLUSIONS: Fluconazole treatment did not reduce urine output or improve urine concentrating ability in adult patients with congenital AVP-R.