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Nephrogenic diabetes insipidus
Clinical feature:
Definition: 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.
History: 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.
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.
Epidemiology: Approximately 90% of patients are males suffering from x-linked diabetes insipidus. The remaining 10% are autosomal recessive.
Clinical picture: 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.
Diagnostics:
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.
Differential: 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.
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