並列摘要
The incidence of hereditary nephrogenic diabetes insipidus (NDI) is estimated to be approximately 9 in 1 million male live births for the most common X-linked variety representing about 90% of patients. It is characterized by a loss of arginine-vasopressin (AVP)-mediated antidiuresis. It belongs to a large group of protein-misfolding diseases. In congenital NDI that results from mutations in the AVPR2 gene that encodes the V2 receptor, most missense mutations are misfolded, trapped in the endoplasmic reticulum and unable to reach the basolateral membrane to engage the circulating antidiuretic hormone AVP. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance and is secondary to mutations in the aquaporin-2 gene (AQP2). Mutant AQP2 proteins are also misrouted. Mutants that encode other renal membrane proteins that are responsible for Gitelman syndrome, Bartter syndrome and cystinuria are also retained in the endoplasmic reticulum. The purpose of this review is to first describe in molecular terms the regulated transepithelial water permeability of the collecting ducts then to describe two types of hereditary nephrogenic diabetes insipidus: a pure type characterized by loss of water only, and a complex type characterized by loss of water and ions. Patients with hereditary NDI bearing mutations in AVPR2, the gene coding for the arginine vasopressin 2 receptor, or in AQP2, the gene coding for the vasopressin-sensitive water channel, have a pure NDI phenotype with loss of water, but normal conservation of sodium, potassium, chloride, and calcium. Patients bearing inactivating mutations in one of the five genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium.