By studying how kidney stone crystals grow at the nanoscale
level, scientists were able to identify molecules that were similar
enough to attach to the crystal but different enough to prevent
further growth. The new strategy might prove an effective way
to block kidney stone formation.
Atomic force microscope image of a growing L-cystine
crystal shows stacks of hexagon-shaped plates. Image
by Rimer et al., courtesy of Science.
Kidney stones are hard masses that develop from crystals that
build up in the kidneys. Most can travel from the kidney and
through the urinary tract before they grow large enough to cause
any problems. But in some people, the crystals enlarge, clump
together and lodge in the kidney, bladder or urinary tract, bringing
A rare type of kidney stone made of the amino acid L-cystine
affects about 20,000 people nationwide. Affected people have
an inherited condition called cystinuria. L-cystine stones are
larger, recur more often and are more likely to cause chronic
kidney disease than are the more common kidney stones made of
calcium oxylate. L-cystine stones are also more difficult to
treat. Current approaches can suppress but may not completely
prevent crystal formation, and some therapies have negative side
As reported in the October 15, 2010, issue of Science,
the investigators found that L-cystine crystals form pyramids
of hexagon-shaped plates. The plates have "steps" on
their surfaces that grow in a spiral fashion as L-cystine molecules
continually attach to their edges.
In hope of slowing crystal growth, the researchers identified
2 synthetic compounds—called L-cystine dimethylester (L-CDME)
and L-cystine methylester (L-CME)—that are chemically similar
to L-cystine but have different groups of atoms at both ends.
Again using atomic force microscopy, the scientists observed
crystal formation after either of the synthetic compounds was
added to the mix.
The researchers found that the compounds essentially acted like
chemical "imposters" by attaching to sites for crystal
growth but then blocking the attachment of additional L-cystine
building blocks. The edges of the hexagon-shaped pyramid became
more ragged and misshapen.
Additional analyses showed that the compounds reduced overall
crystal production and crystal size. L-cystine crystals grown
in the presence of L-CDME tend to form a hexagon-shaped needle-like
structure that's about 1,000-times smaller than typical L-cystine
"This may lead to a new approach to preventing cystine
stones simply by stopping crystallization," says Ward. He
and his colleagues note, however, that their research is still
in its early stages, and the crystal inhibitors may work differently
in the body than in the laboratory. Further research is needed
to test the compounds effectiveness in animal models.