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Heterogeneity in Calcium-based Nephrolithiasis from a Materials Perspective

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Sources of Funding: None

Introduction

Routine clinical stone analytics fail to accurately characterize nuances in structure, composition, and mechanical properties of stone specimens. Using analytical approaches not routinely used in clinical setting, we sought to uncover similarities and differences in structure, chemical composition, and mechanical properties of the most common forms of calcium nephrolithiasis.

Methods

After endoscopic extraction, human calcium-based stones deemed "pure" (100% calcium oxalate or 100% calcium apatite) by routine clinical Fourier Transmission Infrared stone analysis were selected for further analysis. All stones were then subjected to light microscopy, micro-computed tomography (CT), digital segmentation mineral density analysis, Knoop microindentation, energy dispersive x-ray analysis, and inductively coupled plasma mass spectroscopy (ICP-MS).

Results

All CaOx and apatite stones demonstrated highly variable regions of mineral density. In CaOx stones, mineral density distributions revealed areas of low (593.3 ± 84.6 mg/cc), medium (842.0 ± 139.4 mg/cc), and high (1127 ± 244.9 mg/cc) density regions. Apatite stones also contained regions of low (694.8 ± 232.5 mg/cc), medium (1096.1 ± 174.6 mg/cc) and high (1420.3 ± 141.8 mg/cc) density which varied within layers extending from single or multiple nucleation sites. Microindentation revealed that, despite having lower average mineral density, CaOx stones demonstrated higher material hardness compared to apatite stones. Energy dispersive x-ray analysis detected organic matter (carbon concentration) between distinct morphologic layers in CaOx stones, whereas apatite stones contained organic material within stratified layers. ICP revealed numerous trace elements in both stone types.

Conclusions

Using advanced analytic techniques, calcium based calculi were found to have significant heterogeneity in structure, density, material hardness, and mineral composition that is not elucidated by routine clinical testing. Despite traditional thinking, stone density does not directly correlate with mechanical hardness. Underlying stone heterogeneity may help explain why historical approaches have failed in predicting stone types and response to lithotripsy.

Funding

None

Authors
Benjamin Sherer
Ling Chen
Ryan Hsi
David Killilea
Sunita Ho
Marshall Stoller
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