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Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus

Nature Reviews Nephrology volume 11, pages 576–588 (2015)Cite this article

Subjects

Key Points

  • Nephrogenic diabetes insipidus (NDI) is caused by inability of the kidneys to concentrate urine by reabsorbing water in the collecting duct

  • NDI can be inherited (X-linked or autosomal) or acquired, most commonly as a result of lithium treatment

  • Management of primary forms of NDI focuses on dietary modification to reduce osmotic load and pharmacological treatment with inhibitors of prostaglandin synthesis and thiazide diuretics

  • With appropriate treatment, complications of NDI—such as failure to thrive and mental retardation resulting from repeated hypernatraemic dehydration—can be avoided

  • New treatment approaches for congenital NDI have been tested in animal models, but efficacy in patients has not yet been confirmed

Abstract

Healthy kidneys maintain fluid and electrolyte homoeostasis by adjusting urine volume and composition according to physiological needs. The final urine composition is determined in the last tubular segment: the collecting duct. Water permeability in the collecting duct is regulated by arginine vasopressin (AVP). Secretion of AVP from the neurohypophysis is regulated by a complex signalling network that involves osmosensors, barosensors and volume sensors. AVP facilitates aquaporin (AQP)-mediated water reabsorption via activation of the vasopressin V2 receptor (AVPR2) in the collecting duct, thus enabling concentration of urine. In nephrogenic diabetes insipidus (NDI), inability of the kidneys to respond to AVP results in functional AQP deficiency. Consequently, affected patients have constant diuresis, resulting in large volumes of dilute urine. Primary forms of NDI result from mutations in the genes that encode the key proteins AVPR2 and AQP2, whereas secondary forms are associated with biochemical abnormalities, obstructive uropathy or the use of certain medications, particularly lithium. Treatment of the disease is informed by identification of the underlying cause. Here we review the clinical aspects and diagnosis of NDI, the various aetiologies, current treatment options and potential future developments.

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Figure 1: The renal concentration and dilution mechanism.
Figure 2: Regulation of vasopressin secretion.
Figure 3: Water transport in the principal cell.
Figure 4: Timeline of key advances in the understanding of nephrogenic diabetes insipidus.

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Article 08 August 2019

Mirjam Christ-Crain, Daniel G. Bichet, … Alan S. Verkman

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Acknowledgements

D.B.'s work is supported by the Higher Education Funding Council for England and the European Consortium for High-Throughput Research in Rare Kidney Diseases (grant 2012-305608).

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  1. University College London Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Detlef Bockenhauer

  2. Departments of Medicine and Molecular and Integrative Physiology, Université de Montréal Research Center, Hôpital du Sacré-Coeur de Montréal, 5400 Boulevard Gouin Ouest, Montréal, H4J 1C5, QC, Canada

    Daniel G. Bichet

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Bockenhauer, D., Bichet, D. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol 11, 576–588 (2015). https://doi.org/10.1038/nrneph.2015.89

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