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Multimodal imaging reveals a unique autofluorescence signature of Randall’s plaque

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Abstract

Kidney stones frequently develop as an overgrowth on Randall’s plaque (RP) which is formed in the papillary interstitium. The organic composition of RP is distinct from stone matrix in that RP contains fibrillar collagen; RP in tissue has also been shown to have two proteins that are also found in stones, but otherwise the molecular constituents of RP are unstudied. We hypothesized that RP contains unique organic molecules that can be differentiated from the stone overgrowth by fluorescence. To test this, we used micro-CT-guided polishing to expose the interior of kidney stones for multimodal imaging with multiphoton, confocal and infrared microscopy. We detected a blue autofluorescence signature unique to RP, the specificity of which was also confirmed in papillary tissue from patients with stone disease. High-resolution mineral mapping of the stone also showed a transition from the apatite within RP to the calcium oxalate in the overgrowth, demonstrating the molecular and spatial transition from the tissue to the urine. This work provides a systematic and practical approach to uncover specific fluorescence signatures which correlate with mineral type, verifies previous observations regarding mineral overgrowth onto RP and identifies a novel autofluorescence signature of RP demonstrating RP’s unique molecular composition.

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Acknowledgements

We thank Sharon Bledsoe and Tony Gardner for assistance with data collection. This work was funded by the following grants from the National Institutes of Health: P01 DK056788; R01 DK124776, and S10 RR023710

Funding

NIH P01 DK056788; NIH R01 DK124776; NIH S10 RR023710.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Seth Winfree & Tarek M. El-Achkar

  2. Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA

    Seth Winfree, Courtney Weiler, Sharon B. Bledsoe, Tony Gardner, Andrew P. Evan, Tarek M. El-Achkar & James C. Williams Jr.

  3. Molecular Microspectroscopy Laboratory, Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA

    André J. Sommer

  4. Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA

    James E. Lingeman & Amy E. Krambeck

  5. Division of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA

    Elaine M. Worcester

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  1. Seth Winfree
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  2. Courtney Weiler
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  3. Sharon B. Bledsoe
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  4. Tony Gardner
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  5. André J. Sommer
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  6. Andrew P. Evan
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  7. James E. Lingeman
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  10. Tarek M. El-Achkar
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  11. James C. Williams Jr.
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This is a multi-center study, and all authors were involved in data collection and manuscript review.

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Correspondence to James C. Williams Jr..

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Local Internal Review Board approved stone collection from patients.

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Winfree, S., Weiler, C., Bledsoe, S.B. et al. Multimodal imaging reveals a unique autofluorescence signature of Randall’s plaque. Urolithiasis 49, 123–135 (2021). https://doi.org/10.1007/s00240-020-01216-4

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  • DOI: https://doi.org/10.1007/s00240-020-01216-4

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