Navy enlists Sakhaee in study of bottlenose dolphins

By Robin Russell / September 2011

When the U.S. Navy learned that its fleet of bottlenose dolphins was prone to developing kidney stones, personnel began searching for a national expert to help find the underlying causes.

They turned to Dr. Khashayar Sakhaee, chief of mineral metabolism, who has headed decades of kidney stone research projects funded by the National Institutes of Health.

“Our understanding of the pathophysiology of kidney stone formation allowed us to map a logical hypothesis to overcome this problem,” Dr. Sakhaee said.

Marine mammal handler Gunner's Mate 3rd Class Manuel Gonzalez and a bottlenose dolphin are both assigned to Explosive Ordnance Disposal Mobile Unit (EODMU) 1.

The Office of Naval Research now has given UT Southwestern a grant of more than $800,000 to understand the mechanism of why dolphins develop kidney stones and to determine how to prevent and treat kidney stone disease in the marine mammals, which are used by the fleet for underwater force protection and mine detection.

Dr. Sakhaee will be the principle investigator for the research. He will help develop a two-phase study in conjunction with the National Marine Mammal Foundation.

“We will test the hypothesis that combined potassium citrate and citric acid treatment as a stone preventative therapy might successfully treat kidney stones in dolphins,” Dr. Sakhaee said.

The study’s findings will be used to adopt a new treatment strategy for Navy dolphins and a standard clinical practice in the Navy Marine Mammal Program, located in the Biosciences Division of the Space and Naval Warfare Systems Center Pacific in San Diego, Calif.

The research also may have implications for other dolphins, besides those used by the Navy, said Dr. Sakhaee, who is also a professor of internal medicine. Until now, the underlying causes of kidney stone formation in dolphins have not been fully investigated.

Researchers will test potassium citrate, originally developed by The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research to treat kidney stone disease in humans, because of its capacity to decrease urinary ammonium excretion. They will combine it with citric acid because of its ability to minimize urinary alkalinity, thereby reducing the development of ammonium urate in the dolphins.

Recent studies showed that stones in dolphins were associated with anemia and impaired kidney function. Kidney stones in dolphins are primarily ammonium urate, a type of stone detected in various mammals and reptiles, but rarely in humans, Dr. Sakhaee said.

“This may be due to their high intake of very large amounts of protein, which is known to significantly increase urinary ammonium excretion,” he said. “Navy dolphin diets are composed of 73 percent protein. In humans, a high-protein, low-carbohydrate diet has been shown to significantly increase the propensity to form uric acid and calcium stones.”

Phase one of the study will identify physiological, dietary and environmental risk factors for stone formation using serum and urine biomarkers of kidney stone disease; phase two will assess the effectiveness of treatments for stones.

The three-year grant is part of a five-year investment strategy by the National Marine Mammal Foundation to identify research projects that will improve the health of Navy marine mammals. Co-collaborators on the study are Drs. Cynthia Smith, executive director, and Stephanie Venn-Watson, director of clinical research, of the National Marine Mammal Foundation.

Dr. Khashayar Sakhaee is holder of the BeautiControl Cosmetics, Inc. Professorship in Mineral Metabolism and Osteoporosis and the Laura Kim Pak Professorship in Mineral Metabolism Research.