Nephrogenic diabetes insipidus (NDI)

Due to the lack of response of the renal tubules to ADH, urine cannot be concentrated in nephrogenic diabetes insipidus. Clinical symptoms include polyuria, polydipsia, fever, constipation, and acute hypertonic dehydration (hypernatraemia) after birth, which may lead to neurological disorders. In untreated children, daily urine volume can exceed 10 litres. The reduced urine osmolarity cannot be corrected by administration of ADH.

The prevalence of nephrogenic diabetes insipidus in newborns is reported to be 1–9 per 1,000,000 boys.

Nephrogenic diabetes insipidus is caused by pathogenic variants that impair the renal response to ADH. In 90% of cases, causative variants are located in the AVPR2 gene on Xq28, which encodes the vasopressin V2 receptor of ADH. Via AVPR2, ADH increases the water permeability of the basolateral membrane of renal tubule cells. In 10% of patients, variants occur in the AQP2 gene, which encodes aquaporin-2, a vasopressin-sensitive water channel of the renal tubules.

Nephrogenic diabetes insipidus is inherited in an X-linked pattern in 90% of cases. The X-linked form manifests clinically only in males, although some heterozygous female carriers show mild symptoms due to variable X-inactivation. Variants in AQP2 account for 10% of cases and can be inherited in an autosomal recessive manner and, in rare cases, in an autosomal dominant manner.

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