The geology of kidney stones revealed

by Mary Caperton Morton
Friday, December 21, 2018

Kidney stones are an excruciatingly painful problem for 10 percent of the world’s population. In a new study applying geobiological methods to the study of human kidney stones, researchers have shed light on how the stones form, and revealed that they partially and repeatedly dissolve inside the kidney — which could help in developing new protocols to treat the pervasive affliction.

Most kidney stones are made of crystallized calcium oxalate, which has been thought to be insoluble in the kidney. To get rid of kidney stones, they must be passed naturally through the body — an extremely painful process — removed invasively through surgery or broken up by lithotripsy using sound waves so they can be more easily passed. After removal, the stones are usually disposed of, with most studies and patient-monitoring efforts focused on urine chemistry, not the stones themselves. “It struck me that most medical doctors don’t really study the stones, but I’ve never met a rock that doesn’t have a history,” says Bruce Fouke, a geobiologist at the University of Illinois at Urbana-Champaign and co-author of the new study published in Scientific Reports.

As both a geologist and microbiologist, Fouke primarily studies naturally occurring mineral buildups such as those that form in coral reefs or oil fields, as well as travertine deposits in hot springs and Roman aqueducts — environments where microbes play important roles in mineralization. “We decided to work up kidney stones in the same way that we study any naturally occurring crystalline deposit. This kind of analysis has never before been done on kidney stones,” he says.

Fouke and his colleagues, including study lead authors Mayandi Sivaguru and Jessica Saw, both at the University of Illinois as well, sliced the kidney stones to a thickness of 20 microns. Then, they imaged the thin slices with a recently developed type of light microscopy called Airyscan super-resolution microscopy. The approach yielded a never-before-seen look at kidney stones and highlighted the interior growth patterns of the stones. “I’ve never seen another rock deposit anywhere on planet Earth — not in caves, oceans, lakes or hot springs — that has this high of a frequency of layering,” Fouke says.

The layers revealed by the microscopy technique were between 50 and 100 nanometers thick, and each stone was made up of tens of thousands of layers. “Using the patient histories, we were able to surmise that each of those layers was laid down on the scale of minutes,” Fouke says. “As it turns out, the best recorder of the physiology and function of the human kidney is the stone itself. That’s one of two big revelations from this study.” The other is that the stones also record a history of substantial crystal dissolution — something that was thought impossible for calcium oxalate stones while they’re still in the kidney. All the stones the researchers studied contained cross-cutting crystals jutting through the fine layers, a hallmark of partial dissolution. “The layers show a clear history of growing, dissolving, recrystallizing and dissolving, resulting in more than 75 percent of the original bulk stone material being dissolved and replaced,” he says.

“This is really beautiful work,” says Saeed Khan, a urologist at the University of Florida who was not involved in the study. “The images are the most detailed ever produced. It’s remarkable to see how kidney stone formation happens, layer by layer.”

The evidence for dissolution is intriguing, Khan says. “But dissolving a few layers of crystals is a long way from dissolving the entire stone.” Still, the finding may open new lines of inquiry into the conditions that accompany dissolution inside the kidney, he says. Other studies have shown that stains applied to the outside of kidney stones can find their way into the interior of the stone. “This means that a change in urine chemistry can affect the entire stone. We may be able to change the urine chemistry and perhaps dissolve the stone, at least partially, in situ,” Khan says.

Fouke and his colleagues plan to continue their work by pairing patient histories with records of kidney stone growth and dissolution to understand the conditions that trigger layers to be laid down or dissolved. “We’re also working on a very detailed analysis of the proteins and peptides that are trapped within the layers, some of which might be catalyzing or inhibiting the rate of growth, much like microbes do in hot springs,” Fouke says. “These combined approaches open up a new world of possibilities for treating kidney stones without painful passage or surgery. If we can figure out how to encourage wholesale stone dissolution inside the kidney, everyone will be very happy.”

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