SCIENTIFIC BACKGROUND

AQP2, AVPR2

Category:

Nephrogenic diabetes insipidus (NDI) is a disease in which the renal tubules do not respond to antidiuretic hormone (ADH), meaning that urine cannot be concentrated. Symptoms include polyuria, polydipsia, fever, constipation, and acute hypertonic dehydration (hypernatremia) after birth, which can lead to neurological disorders. The daily urine volume can exceed 10 liters in untreated children, and the low osmolarity of the urine cannot be corrected by administering ADH.

 

The prevalence in newborns is given as 1-9:1,000,000 boys.

 

In addition to adequate water intake, a diet low in salt, potassium and protein is recommended, as well as the administration of thiazide diuretics together with anti-inflammatory, non-steroidal drugs such as amiloride and/or indomethacin.

 

NDI is inherited in an X-linked pattern in 90% of cases. It is caused by causative variants in the AVPR2 gene on Xq28, which codes for the vasopressin V2 receptor of ADH. Via AVPR2, ADH increases the water permeability of the basolateral membrane of the renal tubule cells. The X-linked form only manifests clinically in males, but some heterozygous female carriers have mild symptoms of NDI due to variable X-inactivation. In 10% of patients, there is a variant in the AQP2 gene, which codes for aquaporin-2, a vasopressin-sensitive water channel of the renal tubules. AQP2 mutations can be inherited in an autosomal recessive manner, in rare cases also in an autosomal dominant manner.

 

References

Kavanagh et Uy 2019, Pediatr Clin North Am 66:227 / Sharma et al. 2018, Clin Kidney J 12:180 / Bichet et Bochkenhauer 2016, Best Pract Res Clin Endocrinol Metab 30:263 / Spanakis et al. 2008, J Cell Physiol 217:605 / Fujiwara et Bichet 2005, J Am Soc Nephrol 16: 2836 / Mizuno et al. 2003, Horm Res 59: 297 / Arthus et al. 2000, J Am Soc Nephrol 11:1044 / Pan et al. 1992, Nat Genet 2: 103

GENES

AQP2, AVPR2

ASSOCIATED TESTS

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