Geobiology reveals how human kidney stones dissolve in vivo

Abstract

More than 10% of the global human population is now afflicted with kidney stones, which are commonly associated with other significant health problems including diabetes, hypertension and obesity. Nearly 70% of these stones are primarily composed of calcium oxalate, a mineral previously assumed to be effectively insoluble within the kidney. This has limited currently available treatment options to painful passage and/or invasive surgical procedures. We analyze kidney stone thin sections with a combination of optical techniques, which include bright field, polarization, confocal and super-resolution nanometer-scale auto-fluorescence microscopy. Here we demonstrate using interdisciplinary geology and biology (geobiology) approaches that calcium oxalate stones undergo multiple events of dissolution as they crystallize and grow within the kidney. These observations open a fundamentally new paradigm for clinical approaches that include in vivo stone dissolution and identify high-frequency layering of organic matter and minerals as a template for biomineralization in natural and engineered settings.

Figure 1

Historical sequence of events (HSE) constructed from super-resolution auto-fluorescence (SRAF) images of the MP2 calcium oxalate (CaOx) kidney stone. (a) The HSE. (b) Sketch depicting individual HSE events. (c) Representative SRAF image composed of merged three pseudo-colored red, green and blue (RGB) channels. Brightness and contrast of the RGB channel intensities are adjusted to highlight the dark crystalline fabrics. Raw images with and without adjustments are presented in Supplementary Fig. 2.

Figure 2

Evidence for in vivo dissolution and nano-layering from confocal auto-fluorescence (CAF) and SRAF imaging of the MP2 CaOx kidney stone. Specific areas of the MP2 stone from which these image enlargements are made are shown in Supplementary Fig. 1. (a) Tiled CAF image of merged pseudo-colored RGB channels with no image adjustments. (b,c) SRAF images of merged pseudo-colored RGB channels. The brightness and contrast of each image is individually adjusted to highlight the layered crystalline architecture (raw images with and without adjustments are presented in Supplementary Fig. 22). (d) SRAF image of COM_C nano-layering from merged two-channel blue and red (pseudo-colored cyan) channels (Z-stack optical sections of all layers are presented in Supplementary Video 2). The SRAF green channel is identical to the red channel (pseudo-colored cyan) and therefore not included. (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 (CPOLPC) image shows COM_C dark organic matter-rich and light mineral-rich nano-layering with enlargement (g). The original color image of the same area is presented in Supplementary Fig. 18. Images (d,e) are displayed with best-fit intensity profiles. Images (f,g) are displayed with best-fit intensity profiles after a gamma correction of 0.4.