A journey into a human kidney

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 findingschallenge 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, imaging 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 said.

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”, says Dr. Sivaguru.

ZEISS LSM 880 Airyscan superresolution image showing nanolayers and massive dissolution of Euhedral COD crystals and recrystallization of COM crystal inside the void space, Image provided by Mayandi Sivaguru, Jessica Saw and Bruce Fouke. POL only and POL and Phase contrast (Top left and right, respectively); Crossed Nicols Vs Circular Polarization (bottom left and right, respectively) images showing improved visualization of nanolayers (confirmation of inset from Fourier frequency space). Image provided by Mayandi Sivaguru, Jessica Saw and Bruce Fouke.

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.

Dissolution of COM crystals via Mimetic Replacement (encircled areas in circular polarization image (top) and corresponding Airyscan Superresolution image (bottom). Note at the dotted lines the high frequency layering is dissolved and mimetically replaced at Angstrom level. Image provided by Mayandi Sivaguru, Jessica Saw and Bruce Fouke.

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.

[embedded content]

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