Nephrogenic diabetes insipidus: potential treatments and their mechanisms of action.

Nephrogenic diabetes insipidus (NDI) is a rare disease caused by the complete or partial resistance of the kidneys to antidiuretic hormone (ADH). NDI associated with excessive urine production and severe thirst. There are two types of NDI; acquired NDI and congenital NDI.   Acquired NDI is the most common type among adults, with several factors that can cause acquired NDI, for instance, lithium therapy and electrical disorders. Congenital NDI can occur due to mutations in either the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin-2 (AQP2) gene. New effective treatments for NDI are required because the disease can be life treating if left untreated. Current animal studies showed that rolipram and metformin are two potential treatments for congenital NDI by upregulation the apical expression of AQP2 channels. Other animal studies illustrated that the combination of different drugs, such as, secretin agonist and fluvastatin could be an effective method to treat XNDI. Furthermore, some agents were found to be able to treat more than one type of NDI, for example, sildenafil citrate could be potently used to treat acquired NDI and XNDI, while statins could be promising treatments for congenital NDI and autosomal NDI. However, further investigation and human trials are needed before it can be decided if these drugs can be clinically used as a treatment for NDI.