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Current Research Projects:
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Interest in astronaut dehydration and rehydration grew out of the similarities between the physiology of astronauts in space and dehydrating illnesses, the commonest cause of death worldwide in children under two years of age.
In weightlessness, large amounts of calcium come out of the astronauts' bones. The calcium in the blood is filtered into the kidneys, where it creates a concentrating defect, in association with a resetting of the relationship between plasma osmolarity and the hormones that regulate osmolarity. The osmolar regulatory hormones, such as anti-diuretic hormone, become ineffective at preventing further water loss from the kidneys, as the kidneys have a calcium-induced inability to respond by concentrating the urine. High calcium in the urine in the setting of dehydration greatly predisposes astronauts to renal stone formation. Rehydration attempts without correction of the hypercalcemia aggravates the situation, by simply washing more calcium from the blood into the kidneys.<
Children under two naturally have high levels of calcium in their blood and an inability to concentrate their urine. As in the astronauts' dehydration, attempts to rehydrate without correction of the hypercalcemia aggravates the situation, by simply washing more calcium from the blood into the kidneys.
The molecular mechanisms of calcium-induced concentrating defects in the kidneys have recently been elucidated. A receptor in the kidney, known as the extracellular calcium sensing receptor, binds calcium-inducing removal of aquaporin water channels from the tubule lumens, inhibiting the kidneys' ability to concentrate urine. Understanding these mechanisms allows us to intervene in this pathophysiology to prevent the self-propagating cycle, correct the dehydration, and prevent renal stone formation.
| Specific Aim I. | To determine the role of the extracellular calcium sensing receptor as a mediator of hypercalcemic concentrating defect. |
| Specific Aim II. | To determine the efficacy of heavy metals and receptor specific peptides in reversing the hypercalcemia concentrating defect. |
| Specific Aim III. | To determine if heavy metals and receptor specific peptides can reverse hypercalcemia due to bone efflux of calcium. |
Dehydration in Children from the Medical Coolege of Georgia
