Urinary content of aquaporin 1 and 2 in nephrogenic diabetes insipidus

Abstract

Hereditary nephrogenic diabetes insipidus (NDI) is caused by mutations in either the X-chromosomal gene encoding the vasopressin V2-receptor or in the autosomal gene encoding aquaporin-2. Expressed in Xenopus oocytes, the AQP2 gene mutations found in NDI have been shown to reduce the stability of the encoded protein. This study investigated the in vivo stability of mutant and wild-type aquaporin-2 proteins by measuring their excretion in urine of NDI patients and healthy individuals. On immunoblots, the urine samples from healthy volunteers revealed clear aquaporin-1 and aquaporin-2 signals in antidiuretic but not diuretic states. In the urine of a female patient, whose NDI is explained by low expression of the wild-type V2-receptor gene, aquaporin-2 excretion was high and comparable with that in a healthy individual during antidiuresis. In the urine of a male patient with a non- sense mutation in the V2-receptor gene, a weak aquaporin-2 signal was detected. In NDI patients with mutations in the aquaporin-2 gene, aquaporin- 2 could not be detected in urine, suggesting a low stability of mutant aquaporin-2 proteins. In four out of seven NDI patients, aquaporin-1 excretion was relatively high, which suggests a compensatory increase in proximal reabsorption in NDI.