Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.
The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.
UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. d.bockenhauer@ucl.ac.uk
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D051399:Aquaporin 2 / Q000172:deficiency / Q000235:genetics*; D001477:Bartter Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005198:Fanconi Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007008:Hypokalemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000235:genetics*
C496023:AQP2 protein, human; D051399:Aquaporin 2; D017483:Receptors, Vasopressin