Hereditary polyuric disorders: new concepts and differential diagnosis.

The identification, characterization, and mutational analysis of genes coding for key proteins to the mechanisms of urine concentration provide the basis for understanding the 2 types of hereditary nephrogenic diabetes insipidus (NDI): 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 1 of the 5 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.