Kidney discovery defies medical wisdom
Image: Fluorescence micrograph of a human kidney stone from the Mayo Clinic [Illinois].
Using a dazzling array of optical methods, US-based researchers have discovered that kidney stones are built up in calcium-rich layers that dissolve and re-grow within the kidney.
The discovery contradicts medical convention that states calcium oxalate stones are homogenous rocks that never dissolve and are different from all other rocks in nature.
Fluorescence micrograph of a human kidney stone from the Mayo Clinic. Image provided by Mayandi Sivaguru, Jessica Saw from Bruce Fouke Lab, Carl R. Woese Institute for Genomic Biology, University of Illinois.
“Contrary to what doctors learn in their medical training, we found that kidney stones undergo a dynamic process of growing and dissolving, growing and dissolving,” says Professor Bruce Fouke from the University of Illinois. “This means that one day we may be able to intervene to fully dissolve the stones right in the patient’s kidney, something most doctors today would say is impossible."
“Instead of being worthless crystalline lumps, kidney stones are a minute-by-minute record of the health and functioning of a person’s kidney,” he adds.
Fouke and colleagues analysed kidney stone thin section using a combination of optical techniques including bright field, polarization, confocal and super-resolution nanometre-scale auto-fluorescence microscopy.
For example, as Fouke highlights in Nature Scientific Reports, the researchers used confocal auto-fluorescence and Airyscan super-resolution methods, via a Zeiss LSM 880 Laser Scanning Microscope, to observe nano-layers within samples.
A spectral confocal system, Zeiss LSM 710, and fluorescence-lifetime imaging microscopy were also used to distinguish the auto-fluorescence emissions produced by organic matter trapped within the calcium oxalate crystals, from those produced by the epoxy required to impregnate and mount the stones.
Evidence for in vivo dissolution and nano-layering from confocal auto-fluorescence and super-resolution auto-fluorescence imaging of a CaOx kidney stone. (a) Tiled confocal auto-fluorescence image of merged pseudo-colored RGB channels with no image adjustments. (b,c) super-resolution auto-fluorescence images of merged pseudo-colored RGB channels. (d) super-resolution auto-fluorescence image of nano-layering from merged two-channel blue and red (pseudo-colored cyan) channels. (e) Individual ~140 nm-thick dark and light nano-layers (open and closed arrowheads) with enlargement (e). Radiating twinned crystals grow with their c-axis oriented perpendicular to each dark or light nano-layer (arrows). (f) Black and white circular polarization phase contrast image shows dark organic matter-rich and light mineral-rich nano-layering with enlargement (g). [Scientific Reports, Volume 8, Article number: 13731 (2018)]
"Many of the techniques are commonly employed in geology and geobiology, but have not been used to study mineralizations in living organisms, like the kidney stones and gallstones that form in the human body," highlights Fouke. "In particular, the use of ultraviolet light, which causes some minerals and proteins to fluoresce at different wavelengths, offered a vast new treasure trove of information."
Airyscan super-resolution microscopy allowed the team to view the samples at 140 nm resolution, yielding spectacularly clear images of the kidney stone interior with its alternating thin layers of organic matter and crystals.
“Before this study, it was thought that a kidney stone is just a simple crystal that gets bigger over time,” says Jessica Saw from the Mayo Clinic School of Medicine and University of Illinois. “What we’re seeing here is that it’s dynamic. The stone is growing and dissolving, growing and dissolving. It’s very rich with many components. It’s very much alive.”
Research is published in Nature Scientific Reports.