Kidney stone formation is an example of "ectopic calcification," in which calcium hydroxyapatite, a normal constituent of bones and teeth, forms elsewhere. Understanding how kidney stones form may also shed light on other sites of ectopic calcification, such as the coronary arteries.
In many animal models of kidney stones, researchers feed toxins such as antifreeze ethylene glycol to induce the condition. Obviously, this is not how the human condition begins. However, fruit flies with a mutation in the gene that encodes the enzyme xanthine dehydrogenase develop kidney stones that are remarkably like their human counterparts, rich in calcium hydroxyapatite.
Dr. Chi and his colleagues used the fly model to look for genes which, when silenced, prevent or ameliorate kidney stones. The researchers scrutinized over 80 genes, based on known functions, and narrowed them down to fewer than 10 that are involved with formation of kidney stones. Genes related to zinc transport in particular seemed to play a major role, demonstrating the importance of the element in stone formation.
The researchers developed a visually striking method to watch fly kidney stones form. They labeled calcium hydroxyapatite with fluorescent bisphosphonate, an osteoporosis drug. The technique reveals tiny green glowing balls that are the seeds of kidney stones.
Dr. Chi calls the beginnings of the stones "calcified nanoparticles" and puts their size into perspective. "If you had a rope from Hong Kong to San Francisco, to find a calcified nanoparticle, you'd be looking for a 5 to 10 foot segment on that rope." The nanoparticles in the fly may be an early equivalent of precursor lesions in people called Randall plaques, he added.
Zinc transport is im
|Contact: Phyllis Edelman|
Genetics Society of America