Nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to the antidiuretic hormone arginine vasopressin (AVP) which leads to polyuria, plasma hyperosmolarity, polydipsia and impaired quality of living. Inherited forms are caused by X-linked loss-of-function mutations in the gene encoding the vasopressin 2- receptor (V2R) or autosomal mutations in the gene encoding aquaporin 2 (AQP2). A common acquired form is lithium-induced NDI. AVP facilitates reabsorption of water through increased abundance and insertion of AQP2 in the apical membrane of the principal cells in the collecting ducts. In X-linked NDI, the V2R is dysfunctional, which leads to impaired water reabsorption. These patients have functional AQP2 and thus the challenge is to achieve AQP2 membrane insertion independently of the V2R. Current treatment is symptomatic, and is based on distally acting diuretics (thiazide, amiloride) and COX-inhibitors (indomethacin). The review covers published data from trials inpreclinical in vivo models and human intervention studies to improve NDI by more causal approaches. Promising effects on NDI in preclinical studies have been demonstrated by use of pharmacological approaches with secretin, Wnt5a, protein kinase A agonist, fluconazole, prostaglandin E₂ EP2 and EP4 agonists, statins, metformin and soluble prorenin receptor agonists. In patients, only casuistic reports have evaluated the effect of statins, phosphodiesterase inhibitors or a guanylate cyclase stimulator, without amelioration of symptoms. It is concluded that there is currently no established intervention that causally improves symptoms and quality of life in patients with NDI. There is a need to collaborate to improve study quality and conduct formal trials.

中文翻译：

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改善与X连锁性肾病性尿崩症相关的多尿症的药理策略的简要回顾。

肾性尿崩症（NDI）的特征是肾脏对抗利尿激素精氨酸加压素（AVP）的抵抗力，导致多尿，血浆高渗，多饮和生活质量下降。遗传形式是由编码加压素2受体（V2R）的基因中的X连锁功能丧失突变或编码水通道蛋白2（AQP2）的常染色体突变引起的。常见的获取形式是锂诱导的NDI。AVP通过增加丰度和将AQP2插入收集管道中主细胞的顶膜中来促进水的重吸收。在X链接的NDI中，V2R的功能失调，从而导致水的重吸收受损。这些患者具有功能性AQP2，因此挑战在于如何独立于V2R实现AQP2膜插入。目前的治疗是对症治疗，并且基于远端作用的利尿剂（噻嗪类，阿米洛利）和COX抑制剂（吲哚美辛）。该综述涵盖临床前体内模型试验和人为干预研究以通过更多因果关系方法改善NDI的已发表数据。在临床前研究中，通过使用促胰液素，Wnt5a，蛋白激酶A激动剂，氟康唑，前列腺素E的药理学方法已证明了对NDI的有效作用。_2种EP2和EP4激动剂，他汀类药物，二甲双胍和可溶性prorenin受体激动剂。在患者中，只有偶然的报告评估了他汀类药物，磷酸二酯酶抑制剂或鸟苷酸环化酶刺激剂的作用，但并未改善症状。结论是，目前尚无因果改善NDI患者症状和生活质量的既定干预措施。有必要进行合作以提高研究质量并进行正式试验。