Correlation between AVPR2 mutations and urinary AQP2 excretion in patients with nephrogenic diabetes insipidus.

Activation of the V-2 receptor by arginine vasopressin (AVP) results in trafficking of the water channel AQP2 to the luminal plasma membrane and a small amount into the urine. Mutations in the AVPR2 gene, encoding the AVP V-2 receptor, result in congenital nephrogenic diabetes insipidus (CNDI). To determine a correlation between A VPR2 mutations and urinary AQP2 excretion, immunobloting was used to detect AQP2 in the urine of patients with CNDI before and after a dehydration test. The patients' genotype was determined using PCR amplification and direct sequencing of the complete A VPR2 gene. Urinary AQP2 excretion was absent in patients with severely debilitating, mutations, a novel total deletion of the A VPR2 gene, and a novel nonsense mutation W296X. However, it was detected in siblings with a V88M missense mutation. Urinary AQP2 excretion correlated well with other tested phenotype markers. Urinary AQP2 excretion could be used to evaluate the remaining in vivo integrity of the AVP-V-2 receptor-AQP2 cascade in patients with CNDI.