A Journey Into a Human Kidney

ZEISS microscopes help uncover centuries old hidden secrets of human kidney stones

Kidney stones are hard deposits made of minerals and salts that can form inside your kidneys. They have been ascribed no medical value at all, and doctors usually discard them right away. A research team led by Bruce Fouke, a geology and microbiology professor at the University of Illinois, have now shown their complex structure and composition. These findings may lead to better diagnostics and treatment.

A layered history of the kidney’s physiology

Many doctors assume that kidney stones are homogeneous, insoluble, even boring. They either break them using ultrasound leading them to painful passage or more invasively surgically remove them once a pathological stone is brought in to a hospital setting. Recent finding schallenge this 150 year notion that kidney stones could not be dissolved at all, which set the mindset of medical professionals and physicians.

The Carl R. Woese Institute of Biology scientists (from left): Jessica Saw, Bruce Fouke, Mayandi Sivaguru Photo by L. Brian Stauffer

Mayandi Sivaguru (Associate Director of Core Facilities, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, a microscopist), Jessica Saw (an M.D. Ph.D. student from Mayo Clinic) and Bruce Fouke (Professor of Geology and Microbiology and Director of Carver Biotech Center) recently published a paper in the journal Scientific Reports: DOI: 10.1038/s41598-018-31890-9

The team found – unlike the conventional wisdom – that the Calcium oxalate stone which comprise over 70% of all kidney stones could not be dissolved. It is actually undergoing multiple steps of dissolution and recrystallization during the course of its growth.

Instead of looking at these stones as static lumps of crystals, imagine they have a record of daily, if not hourly and minute-by-minute record of bodily fluid, food and metabolism like a record of environment and climate in tree rings and other biomineralization settings in the nature.

Bruce Fouke, Professor of Geology and Microbiology and Director of Carver Biotech Center

Colorful snapshots

Dr. Fouke and his fellow researchers examined more than 50 kidney stone fragments from six Mayo Clinic patients.

A tiled (20×20, 400 images x 3 channels= ~1200 images) 405, 488 and 561 nm ex and their corresponding emission detected using the ZEISS LSM 880 confocal system showing a single stone could be actually a combination of 3 stone complex. Image provided by Mayandi Sivaguru, Jessica Saw and Bruce Fouke.

The team used a variety of optical modalities available at this ZEISS labs@location partner facility. In addition to existing optical techniques from diffraction limit to superresolution, the team has used combination of optical techniques which are never tried before to retrieve high-frequency layering information as in this example, where a phase contrast technique is coupled with either crossed nicols polarization or circular polarization, which enabled to both visualize and quantify high frequency nano-layering.

We left no crystals un-turned.

Mayandi Sivaguru, Associate Director of Core Facilities, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign

This is the first time the authors employed autofluorescence using both the confocal and superresolution modalities of ZEISS LSM 880 with Airyscan. Conventionally, people looked at kidney stones using brightfield, POL and SEM and TEM microscopy.

The images reveal triangles and other geometrics. The disruptive patterns in the stones showed that the vast majority of the material had dissolved and reformed over time.

Future treatment?

Finally, after looking at these human kidney stones under a multitude of optical and electron microscopes the team also provide clinical intervention strategies to start thinking about making new treatments by providing a roadmap for future implications.

The scientists argue that these understandings will help uncover hidden mechanisms of human diseases caused by both dissolution of crystals of calcium phosphate (of bones in the case of arthritis) and crystallization (in the case of arthrosclerosis), thereby treatments could be tailored to preventing them, eventually.

Clinical intervention strategies to dissolve the kidney stones inside kidney rather than using current painful passage or invasive surgeries in the pipeline. Image provided by Mayandi Sivaguru, Jessica Saw and Bruce Fouke.

Doctors often base patient care plans on the chemistry and molecular components of a patient’s urine, yet further research could allow doctors to take advantage of the changing composition of kidney stones themselves. Specific ingredients could then dissolve the stones completely– without painful passage or invasive procedures.

More information on ZEISS Airyscan

Read the New York Times article

A look into history

In 1868, Leslie Beale, a British scientist, first documented calcium oxalates are “difficult to dissolve”. That is where it all started over four years ago, when Prof. Fouke and this team started looking at human kidney stone samples from Mayo Clinic, Rochester patients. Approximately at the same time, Carl Zeiss , Ernst Abbe and Otto Schott make history by producing the first microscopes with science-based optics.

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