Part I of this two-part series discussed a recent breakthrough revealing how human kidney stones actually form much the way rocks form in natural environments: they “undergo previously unforeseen cycles of repeated crystallization, dissolution, fracturing, and faulting.” This process of post-formational physical, chemical, and biological alteration is called diagenesis. The discovery was only possible by joining University of Illinois’ geology and biology (geobiology) forces with Mayo Clinic’s urology and nephrology expertise. The new approach is known as GeoBioMed.

Part II focuses how this breakthrough, along with ongoing research, may open the way for new, unorthodox treatments for kidney stones.

Clinical implications

The study is now at a tipping point in moving toward clinical application. Besides analyzing kidney stones removed from Mayo patients, Bruce Fouke, Ph.D., geobiologist and director of the Roy J. Carver Biotechnology Center, and his team have been able to grow stones in a microfluidic test bed called the GeoBioCell. In it, different bacteria and proteins are added, one at a time, to study how the microbiome might affect stone growth in the human body. Further, the lab has already been able to reverse the course of a kidney stone’s layering process on some level. 

Now that all the tools are in place, the team can start doing more systematic tests, which might also include adding plant extracts, or citrate, for example. Another test would change the amount of water that is present at different times within the growth of the stones.

Laser scanning microscopy images of a human kidney stone produce photographs with a resolution of billionths of a meter.

These new systematic tests may help change the way kidney stones are analyzed and processed in the clinical setting. How? The paper implies that a “stone biopsy” could be done in much the same way a biopsy from, say, breast tissue is immediately examined for cancer by a pathologist. The doctor would then have a better idea of what kind of kidney stone it is (most are made of calcium oxalate, but they can also be struvite, uric acid, or cystine and other mineralogical types), and thus make more informed decisions toward treatment.

Mayandi Sivaguru, Ph.D., is a plant biologist and microscopist at the University of Illinois. “Once it’s removed from the patient, a stone could conceivably be analyzed outside the OR while the patient is still on the operating table,” he says. “For example, we could potentially use a portable lab outside the OR [at Mayo] to understand and identify, very quickly, the type and paragenetic sequence of minerals developing in that particular patient. So then, we could give the patient a specific remedy while they’re still in surgery, and also make a very quick assessment of what needs to be done so that this person will not have to come back to the clinic.”

This would be an important advancement, considering that a stone normally must be sent out for analysis, which can take days or weeks. Identifying the minerology and growth history of a stone could reduce their recurrence by treating the kidney directly with specific compounds that could dissolve the fine breakage fragments often left behind after procedures such as shock-pulse lithotripsy, laser ablation, and ureteroscopy, in which the stone is broken up with special tools inserted inside the kidney. These leftover micro- to nano-scale fragments have the potential to regrow into bigger stones.

Remedies would also be used to encourage stone(s) within the kidney to remain in dissolution mode and thus not grow too big to be passed — an important potential treatment, considering the likelihood of a stone recurring is approximately 70 percent.

“This may be an area where we can either stop growth of these tiny stones before they get too big, or perhaps even dissolve bigger stones more slowly over time,” says John Lieske, M.D.,nephrologist and director of Mayo Clinic’s Rare Kidney Stone Consortium, who co-leads the team.

The portable lab could also be used in private clinical settings.

Kidney stones are transported from Mayo Clinic operating rooms to the University of Illinois Urbana-Champaign for further GeoBioMed analyses. Elena Wilson (Illinois Molecular and Cellular Biology B.Sc., Mayo Clinic SURF Fellow) uses rock cutting saws and polishing lap wheels to carefully orient, cut, and thin section human kidney stones in the Illinois Microscopy and Imaging Core Facility of Carl R. Woese Institute for Genomic Biology.

“Once you retrieve a stone that has been passed or surgically removed by the patient, you would embed the stone in epoxy, which would setup immediately, like Crazy Glue does,” says Dr. Sivaguru. “Then you would polish it down, put it under a UV microscope to take a look, do a quick CT scan on it, and in 15 or 20 minutes you’d get a pretty good idea of what kind of stone you have, and its specific paragenetic sequence.”

This would allow the clinician to plug the stone into the new classification scheme and chemical predictive model. The combination of these two components would reveal the history of the stone’s growth, which will speak to possible remedies.  

Elena Wilson is a former member of Dr. Fouke’s lab team and current post-baccalaureate  fellow at the National Cancer Institute (NIH), who watched these discoveries unfold firsthand. “Ultimately, this experience has showed me that research has the power to put each pathology into perspective and that innovation is reliant on strong collaboration,” she says, “a willingness to think outside of the box, and a trust in the foundational biologic principles from which we continue to make scientific progress.”

The future looks bright

Considering the significant breakthroughs already gained by the GeoBioMed project, the road ahead seems paved for new treatments and interventions for kidney stones. In fact, Dr. Fouke brims with optimism.

“Given the new classification scheme for kidney stones, given our ability to make predictions based on the chemistry of the urine and other components — and then being able to test it directly — means we’re at this really dynamic juncture in this one-of-a-kind collaboration,” Dr. Fouke says.

“We think it has set us up to really go to the heart of new clinical interventions, and also diagnoses in the OR or a clinical setting. There’s no way we could have ever made these breakthroughs without this interdisciplinary collaboration. The future is incredibly bright for us as a team.”

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