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Congenital nephrogenic diabetes insipidus: the current state of affairs

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Abstract

The anti-diuretic hormone arginine vasopressin (AVP) is released from the pituitary upon hypovolemia or hypernatremia, and regulates water reabsorption in the renal collecting duct principal cells. Binding of AVP to the arginine vasopressin receptor type 2 (AVPR2) in the basolateral membrane leads to translocation of aquaporin 2 (AQP2) water channels to the apical membrane of the collecting duct principal cells, inducing water permeability of the membrane. This results in water reabsorption from the pro-urine into the medullary interstitium following an osmotic gradient. Congenital nephrogenic diabetes insipidus (NDI) is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their pro-urine, which leads to a high risk of dehydration. This review focuses on the current knowledge regarding the cell biological aspects of congenital X-linked, autosomal-recessive and autosomal-dominant NDI while specifically addressing the latest developments in the field. Based on deepened mechanistic understanding, new therapeutic strategies are currently being explored, which we also discuss here.

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Authors and Affiliations

  1. Nijmegen Centre for Molecular Life Sciences Graduate School, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Daniel Wesche

  2. Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Peter M. T. Deen

  3. Department of Medical Genetics, University Medical Centre Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands

    Nine V. A. M. Knoers

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Wesche, D., Deen, P.M.T. & Knoers, N.V.A.M. Congenital nephrogenic diabetes insipidus: the current state of affairs. Pediatr Nephrol 27, 2183–2204 (2012). https://doi.org/10.1007/s00467-012-2118-8

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