Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Nephrogenic diabetes insipidus

nephrogenic diabetes insipidus is characterized by the inability of kidney's collecting ducts to concentrate urine in response to arginine-vasopressin. Thus, large amounts of water are excreted despite an elevated arginine-vasopressin level.

Historical Aspects

The French physician Armand Trousseau (1801-1867) published 1862 his lecture on polydipsia, specifically what he called nonsaccharine diabetes. The Latin name diabetes insipidus means tasteless polyuria.

Epidemiology

Approximately 90% of patients are males suffering from x-linked diabetes insipidus. The remaining 10% are autosomal recessive.

Clinical Findings

The clinical picture is dominated by excessive urine volumes accompanied by polydipsia. In the management of the disease, hydrochlorothiazide combined with amiloride and indomethacin has proven to be efficient.

Diagnosis

The diagnosis is made by measuring urine volumes and vasopressin levels. Family history also can help to distinguish between hereditary and acquired forms.

The two forms of nephrogenic diabetes insipidus might be differentiated clinically by vasopressin test. The vasopressin receptor not only mediates the activation of the water channel but also secretion of the coagulation factor VIII and von Willebrand factor, so administration of vasopressin is followed by elevated plasma levels of these factors if the receptor works properly. Hence a normal increase of these factors indicates a defective water channel, the autosomal form of nephrogenic diabetes insipidus, while a defective receptor is the x-linked form.[Error: Macro 'ref' doesn't exist]

Differentials

Important differentials are all acquired forms of polyuria. In case of autosomal recessive inheritance the family history is not instructive. Inherited disorders characterized by the inability to produce the medullary concentration gradient also show an ADH resistant polyuria. ADH resistance slightly increases with age. Responsible for this process are declining renal function, reduced expression of ADH receptors and increased glucosuria due to fading capacity to reabsorb glucose or an unrevealed diabetes mellitus.

Pathogenesis

Two pathogenetic mechanisms are known to cause hereditary diabetes insipidus. Mutations of the vasopressin receptor 2, encoded by the AVPR2 gene, and mutations of the water channel, encoded by the AQP2 gene. AVPR2 mutations show x-linked inheritance. AQP2 mutations ensue autosomal recessive or autosomal dominant inheritance.

Symptoms

Polyuria
Polyuria is prominent as in all forms of diabetes insipidus. In contrast to central diabetes insipidus this does not ameliorate with AVP administration.

Systematic

Hereditary diabetes insipidus
Central diabetes insipidus
Nephrogenic diabetes insipidus
AQP2
AVPR2
Wolfram syndrome

References:

1.

Nguyen MK et al. (2003) Molecular pathogenesis of nephrogenic diabetes insipidus.

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2.

Fujiwara TM et al. (2005) Molecular biology of hereditary diabetes insipidus.

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3.

Noda Y et al. (2005) Trafficking mechanism of water channel aquaporin-2.

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4.

Gade W et al. (2006) A brief survey of aquaporins and their implications for renal physiology.

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5.

Valenti G et al. (2005) Minireview: aquaporin 2 trafficking.

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6.

van Vliet HH et al. (2008) PFA-100 monitoring of von Willebrand factor (VWF) responses to desmopressin (DDAVP) and factor VIII/VWF concentrate substitution in von Willebrand disease type 1 and 2.

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Update: Sept. 26, 2018