Researchers Identify Protein Critical To Urine Concentration

The finding, which will be presented on Sunday, April 19, at the Federation of the American Society of Experimental Biology (FASEB) meeting here, provides fundamental information about how the urine concentrating mechanism works in the kidney.

It also has potential clinical implications for the treatment of diseases associated with fluid retention, or refractory edema, including congestive heart failure and cirrhosis, said the researchers.

"If we could inhibit the water channel with drugs," says A.S. Verkman, MD, PhD, UCSF professor of medicine and physiology, "then problems of fluid retention could be effectively treated where conventional diuretics don't work."

The study was published recently in The Journal of Biological Chemistry (Feb. 20).

Normally, the body produces an unconcentrated urine. However, during times of water deprivation, it must conserve water, and one of the key ways of doing so is to concentrate the urine.

In the UCSF study, the researchers "knocked out," or removed, the gene for the water transporting protein, known as aquaporin 1, which is found widely in animals. They then deprived the mice of water. Within 36 hours, these mice had become severely dehydrated and lethargic, had lost substantial weight, and nearly died. Notably, nearly every mouse was resuscitated by oral water administration. In contrast, mice without the gene deletion continued to thrive, displaying only a moderate weight loss.

"This study," said Verkman, "demonstrates that the missing protein is essential for the mouse kidney to form a concentrated urine."

Moreover, he said, "the dramatic reaction to the deletion of the protein in mice raises the possibility that other mammalian aquaporins have important physiological functions.

"Deletion of each remaining aquaporin in mice is likely to be informative," he says, "as might the screening for aquaporin mutations in genetic diseases associated with abnormalities of fluid balance."