Nephrogenic diabetes insipidus: update of genetic and clinical aspects

Abstract

Ten years have passed since the cloning and molecular identification of the vasopressin V2 receptor (V2R) and aquaporin-2 water channel (AQP2), a pair of molecules whose genetic mutations have been established to cause hereditary nephrogenic diabetes insipidus (NDI), a human disease characterized by an inability to concentrate urine. Gene identification and mutation searches in NDI families have led to the identification of numerous patients, which in turn has provided a more detailed view of the clinical characteristics of this disease entity. Human genetic analyses of these types have also provided insight into how AQP2 protein is regulated inside the cell and how mutant AQP2s come to resist proper regulation. This knowledge of cellular biology will form the basis for the development of new treatments. The present Comment focuses on recent advances in our understanding of the genetic and clinical aspects of NDI.