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Comparison of the pathology of interstitial plaque in human ICSF stone patients to NHERF-1 and THP-null mice

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Abstract

Extensive evidence now supports the role of papillary interstitial deposits—Randall’s plaques—in the formation of stones in the idiopathic, calcium oxalate stone former. These plaques begin as deposits of apatite in the basement membranes of the thin limbs of Henle’s loop, but can grow to become extensive deposits beneath the epithelium covering the papillary surface. Erosion of this covering epithelium allows deposition of calcium oxalate onto this plaque material, and the transition of mineral type and organic material from plaque to stone has been investigated. The fraction of the papilla surface that is covered with Randall’s plaque correlates with stone number in these patients, as well as with urine calcium excretion, and plaque coverage also correlates inversely with urine volume and pH. Two animal models—the NHERF-1 and THP-null mice—have been shown to develop sites of interstitial apatite plaque in the renal papilla. In these animal models, the sites of interstitial plaque in the inner medulla are similar to that found in human idiopathic calcium oxalate stone formers, except that the deposits in the mouse models are not localized solely to the basement membrane of the thin limbs of Henle’s loop, as in humans. This may be due to the different morphology of the human versus mouse papillary region. Both mouse models appear to be important to characterize further in order to determine how well they mimic human kidney stone disease.

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Acknowledgment

This study was funded by NIH P01 DK56788.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 5055S, Indianapolis, IN, 46223, USA

    Andrew P. Evan

  2. Department of Medicine and Physiology, University of Maryland, School of Medicine, Baltimore, MD, USA

    Edward J. Weinman

  3. Departments of Urology and Pathology, New York University School of Medicine, New York, NY, USA

    Xue-Ru Wu

  4. New York Harbor Healthcare System, Manhattan Campus, New York, NY, USA

    Xue-Ru Wu

  5. Methodist Hospital for Kidney Stone Disease, Indiana University School of Medicine, Indianapolis, IN, USA

    James E. Lingeman

  6. University of Chicago School of Medicine, Chicago, IL, USA

    Elaine M. Worcester & Fredric L. Coe

Authors
  1. Andrew P. Evan
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  2. Edward J. Weinman
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  3. Xue-Ru Wu
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  4. James E. Lingeman
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  5. Elaine M. Worcester
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  6. Fredric L. Coe
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Corresponding author

Correspondence to Andrew P. Evan.

Additional information

Proceedings paper from the 3rd International Urolithiasis Research Symposium, Indianapolis, Indiana, USA, December 3-4, 2009.

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Evan, A.P., Weinman, E.J., Wu, XR. et al. Comparison of the pathology of interstitial plaque in human ICSF stone patients to NHERF-1 and THP-null mice. Urol Res 38, 439–452 (2010). https://doi.org/10.1007/s00240-010-0330-1

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  • DOI: https://doi.org/10.1007/s00240-010-0330-1

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