Morin Denis
Département de pédiatrie, hôpital Arnaud-de-Villeneuve, CHU de Montpellier, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex 5, France; Centre de référence des maladies rares du Sud-Ouest, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex 5, France; CNRS UMR 5203, Inserm U661, 141, rue de la Cardonille, 34094 Montpellier cedex 5, France; Université Montpellier I, 34295 Montpellier cedex 5, France.
Nephrol Ther. 2014 Dec;10(7):538-46. doi: 10.1016/j.nephro.2014.09.002. Epub 2014 Oct 25.
Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.
先天性肾性尿崩症是一种罕见的遗传性疾病,主要为X连锁遗传(90%的病例),但也有常染色体隐性和显性形式。先天性肾性尿崩症的特征是肾集合管对精氨酸加压素激素的作用产生抵抗,导致肾脏无法浓缩尿液。X连锁形式是由于加压素2受体基因的失活突变,导致突变受体功能丧失。受影响的男性在新生儿期常出现症状,表现为体重不增、脱水和高钠血症,但也可能出现轻度表型。携带突变的女性可能无症状,但有时由于随机的X染色体失活会出现严重多尿。常染色体隐性和显性形式在男女中均可发生,与水通道蛋白-2基因的突变有关。治疗仍然困难,尤其是在婴儿中,治疗方法是采用低渗饮食、增加水摄入量以及使用噻嗪类药物和吲哚美辛。主要目标是避免高钠血症发作并维持良好的水合状态。在某些X连锁先天性肾性尿崩症病例中,未来可能会有特定的治疗方法,即使用非肽类加压素-2受体拮抗剂等药理伴侣。相反,抗利尿激素分泌失调综合征(NSIAD)与V(2)受体的组成性激活有关,这是由于激活突变导致的,具有抗利尿激素分泌失调的临床和生物学特征,但血浆精氨酸加压素激素水平较低或无法检测到。