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The elementome of calcium-based urinary stones and its role in urolithiasis

Nature Reviews Urology volume 12, pages 543–557 (2015)Cite this article

Subjects

Key Points

  • The majority of human urinary stones are primarily composed of crystalline calcium salts but many other metals and nonmetals are detectable with concentrations ranging over 10 orders of magnitude

  • The contribution of elements other than calcium to the formation, recurrence or physical properties of human urinary stones is generally poorly defined

  • Over the past 50 years, 20–30 studies of elemental stone content have been published and their findings can be summarized to produce a working elementome of the human calcium-based urinary stone

  • The amount of some elements within human calcium-based urinary stones does not correlate with their normal urinary concentrations, suggesting that accumulation or other processes affect the elemental composition of stones

  • Further refinement of the elementome of calcium-based urinary stones is warranted because it is likely to reveal novel opportunities for monitoring lithogenesis and new targets for therapeutic intervention

Abstract

Urolithiasis affects around 10% of the US population with an increasing rate of prevalence, recurrence and penetrance. The causes for the formation of most urinary calculi remain poorly understood, but obtaining the chemical composition of these stones might help identify key aspects of this process and new targets for treatment. The majority of urinary stones are composed of calcium that is complexed in a crystalline matrix with organic and inorganic components. Surprisingly, mitigation of urolithiasis risk by altering calcium homeostasis has not been very effective. Thus, studies to identify other therapeutic stone-specific targets, using proteomics, metabolomics and microscopy techniques, have been conducted, revealing a high level of complexity. The data suggest that numerous metals other than calcium and many nonmetals are present within calculi at measurable levels and several have distinct distribution patterns. Manipulation of the levels of some of these elemental components of calcium-based stones has resulted in clinically beneficial changes in stone chemistry and rate of stone formation. The elementome—the full spectrum of elemental content—of calcium-based urinary calculi is emerging as a new concept in stone research that continues to provide important insights for improved understanding and prevention of urinary stone disease.

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Figure 1: Elemental content of calcium-based urinary stones.
Figure 2: Relationships between the elemental content in calcium-based urinary stones and normal urine.

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Acknowledgements

K.R. and D.W.K. contributed equally to this manuscript. The authors' research is supported by the NIH NIDDK RFA-DK-12-003: Planning Centers for Interdisciplinary Research in Benign Urology (IR-BU)(P20).

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  1. Department of Urology, University of California, San Francisco, 400 Parnassus Avenue, 6th Floor Urology Clinics, San Francisco, 94143, CA, USA

    Krishna Ramaswamy, Thomas Chi & Marshall L. Stoller

  2. Nutrition & Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, 94609, CA, USA

    David W. Killilea

  3. Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, 94945, CA, USA

    Pankaj Kapahi & Arnold J. Kahn

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K.R. and D.W.K. researched data for the article. K.R., D.W.K. and M.L.S. wrote the article. All authors contributed to discussion of the content and reviewed and edited the manuscript before submission.

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Ramaswamy, K., Killilea, D., Kapahi, P. et al. The elementome of calcium-based urinary stones and its role in urolithiasis. Nat Rev Urol 12, 543–557 (2015). https://doi.org/10.1038/nrurol.2015.208

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