NEPHROGENIC DIABETES-INSIPIDUS

In nephrogenic diabetes insipidus, the kidney is unable to concentrate urine despite normal or elevated concentrations of the antidiuretic h ormone arginine vasopressin (AVP). In congenital nephrogenic diabetes insipidus (NDI), the obvious clinical manifestations of the disease, t hat is polyuria and polydipsia, are present at birth and need to be im mediately recognized to avoid severe episodes of dehydration. Most (>9 0%) congenital NDI patients have mutations in the A VPR2 gene, the Xq2 8 gene coding for the vasopressin V-2 (antidiuretic) receptor. In <10% of the families studied, congenital NDI has an autosomal recessive in heritance and mutations of the aquaporin-2 gene (AQP2), ie, the vasopr essin-sensitive water channel, have been identified. When studied in v itro, most AVPR2 mutations lead to receptors that are trapped intracel lularly and are unable to reach the plasma membrane. A minority of the mutant receptors reach the cell surface but are unable to bind AVP or to trigger an intracellular cyclic adenosine-monophosphate (cAMP) sig nal. Similarly AQP2 mutant proteins are trapped intracellularly and ca nnot be expressed at the luminal membrane. The acquired form of NDI is much more common than the congenital form, is almost always less seve re, and is associated with downregulation of AQP2. The advances descri bed here are examples of ''bedside physiology'' and provide diagnostic tools for physicians caring for these patients. (C)1998 by Excerpta M edica, Inc.