A Case of a Novel Mutant Vasopressin Receptor-Dependent Nephrogenic Diabetes Insipidus With Bilateral Non-Obstructive Hydronephrosis in a Middle Aged Man

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Title: A Case of a Novel Mutant Vasopressin Receptor-Dependent Nephrogenic Diabetes Insipidus With Bilateral Non-Obstructive Hydronephrosis in a Middle Aged Man
Authors: Miyakoshi, Masashi; Kamoi, MD, Kyuzi; Uchida, Shinichi; Sasaki, Sei
Publisher: Endocrine Journal
Date Published: December 01, 2003
Reference Number: 641
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We describe a case of a novel mutant vasopressin 2 receptor (V2R)-dependent nephrogenic diabetes insipidus (NDI) with bilateral non-obstructive hydronephrosis in a middle aged man. This could be distinguished from aquaporin 2 (AQP2)-dependent NDI by the response of factor VIII and von Willebrand factor (vWF) to 1-deamino-8-D-arginine vasopressin (DDAVP) administration. A 47-year-old man was admitted to hospital because of polyuria, which had been present from infancy and was suspected of causing non-obstructive hydronephrosis. His mother's father, the older brother of his mother and his second daughter also all had polyuria. Sodium concentration, osmolality and vasopressin in blood were high, while sodium concentration and osmolality in urine were low. There were no changes in urine osmolality, factor VIII and vWF in response to DDAVP infusion. Neither was heart rate, diastolic blood pressure nor facial flushing affected. These findings suggested this case was V2R-dependent NDI rather than AQP2-dependent NDI. Molecular genetic analysis demonstrated that the patient had a V2R missense mutation involving a substitution of cysteine for arginine at position 104 (R104C) located in the first extracellular loop of the V2R. It was also found that the patient's mother and his second daughter were heterozygous for this R104C mutation.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

The ureter is a tube in the body that runs from the kidney to the bladder. When both ureters in a person are blocked, the condition is called bilateral ureteral obstruction. This can cause the pelvis and calices of the kidney to distend with urine, a condition called hydronephrosis. Miyakoshi, et al., describe their analysis of NDI in a 47-year old Japanese man with bilateral non-obstructive hydronephrosis who entered the hospital for treatment of his polyuria, i.e., excessive urination.

His history suggested the possibility of NDI. To see if the causal mutation was either in the AQP2 gene or the V2R gene, the researchers injected the patient with DDAVP, a synthetic analogue of the hormone, arginine vasopressin (AVP). They then measured the patient?s response to this outside the kidney. Specifically, they measured the patient?s heart rate, diastolic blood pressure, facial flushing, and the amount of cAMP in the blood and urine. If there are changes in these parameters, the NDI is caused by a mutation in the AQP2 gene: if there are no changes, the NDI is caused by a mutation in the V2R gene.

The patient?s NDI was caused by a mutation in his V2R gene that produced a structural change in a portion of the V2R protein called the first extracellular loop. This is only the second time this particular mutation has been reported in the literature, and the researchers speculate that the two patients expressing these mutations may have had common ancestors. Finally, this type's mutation may not trigger a serious acute outcome but rather slowly progressive disease.