Nephrogenic diabetes insipidus [Article in Serbian]

Abstract

Nephrogenic diabetes insipidus (NID) is a rare renal disorder characterized by tubular unresponsiveness to arginine-vasopressine (AVP) resulting in the excretion of an increased volume of diluted urine. Congenital (severe) and acquired (mild) forms are recognized. The commonest, X-linked NDI occurs due to mutations in the gene encoding the AVP receptor (AVPR2) located in collecting duct cells. Rarely (10%) NDI may occur as an autosomal recessive due to mutations in the gene coding for the water channel aquaporin 2 (AQP2). In both cases clinical symptoms are similar beginning in infancy, with polyuria and polydipsia with episodes of hypernatremic dehidration, pyrexia, irritability and vomiting. Affected females experience milder symptoms at a later age. Water deprivation and desmopressin tests are essential for both diagnosis and differentiation of NID from central diabetes insipidus and other polyuric disorders. Therapy of NID is symptomatic, aimed at providing adequate water and caloric intake and to reduce both osmotic load and polyuria. Restriction of osmotic load (mainly salt and protein) to 15 mmol/kg/24hr the necessary water intake of 150 ml/kg/24hr is achievable. Thiazides, usually with amiloride, and indomethacin are useful in reducing polyuria but careful monitoring of their adverse effects is obligatory. A treatment with pharmacological chaperons, aimed at restoring the plasma membrane routing of endoplasmatic reticulum retained, but otherwise functional AVPR2 or AQP2 mutants becomes an interesting and promising potential.