Agent curbs kidney stone crystals

NYU (US) — A new method that stops the growth of crystals that form cystine kidney stones suggests a pathway to prevention.

The formation of L-cystine stones is a consequence of excessive levels of L-cystine in the urine. L-cystine forms into crystals, which aggregate into stones, reaching up to a centimeter in diameter.

Using atomic force microscopy—which allows for the observation of objects as small as a nanometer—researchers found that L-cystine crystals grow through the continual attachment of L-cystine molecules to the edges of hexagon-shaped hillocks on the crystal surface. This process results in spiral growth patterns.

Knowing how these crystals grew, the researchers could then select a chemical agent to inhibit this process. Crystal growth can be altered through the use of tailored growth inhibitors.

These inhibitors reduce crystallization rates by binding to crystal surfaces in ways that prevent the addition of crystal molecules to the surface, which is necessary for their normal formation.

Researchers used a synthetic agent, L-CDME, which is structurally identical to L-cystine in its center, but is equipped with different molecular “blocking” groups at the ends designed to prevent the attachment of L-cystine molecules to the crystal surface.

The agent blocked the growth of the L-cystine crystals by binding to L-cystine molecules protruding from the edges of the hexagon-shaped hillocks. Details of the work are reported today in the journal Science.

“This may lead to a new approach to preventing cystine stones simply by stopping crystallization,” explains Michael Ward, the study’s corresponding author and chair of the chemistry department at New York University.

Kidney stones comprised of L-cystine affect at least 20,000 individuals in the United States. This number is substantially smaller than the 10 percent of Americans afflicted by calcium oxalate monohydrate (COM) stones. But L-cystine stones are larger, recur more frequently, and are more likely to cause chronic kidney disease. Current treatments for this disease are somewhat effective, but often lead to adverse side effects.

Current treatments for L-cystine stone prevention, such as dilution through high fluid intake, can suppress, but may not completely prevent, stone formation. Some medications can react with L-cystine to generate more soluble compounds, but these drugs can cause adverse side effects such as nausea, fever, fatigue, skin allergies, and hypersensitivity.

Researchers from NYU and Medical College of Wisconsin contributed to the work.

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