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Structural and chemical heterogeneities of primary hyperoxaluria kidney stones from pediatric patients

  • Author Footnotes
    1 both authors contributed equally and are the first authors.
    Yuan Du
    Footnotes
    1 both authors contributed equally and are the first authors.
    Affiliations
    Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
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  • Author Footnotes
    1 both authors contributed equally and are the first authors.
    Vincent Blay Roger
    Footnotes
    1 both authors contributed equally and are the first authors.
    Affiliations
    Division of Preclinical Education, Biomaterials & Engineering, School of Dentistry, University of California San Francisco, San Francisco, CA, 94143, USA
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  • Jorge Mena
    Affiliations
    Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, 94143, USA
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  • Misun Kang
    Affiliations
    Division of Preclinical Education, Biomaterials & Engineering, School of Dentistry, University of California San Francisco, San Francisco, CA, 94143, USA
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  • Marshall L. Stoller
    Affiliations
    Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, 94143, USA
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  • Sunita P. Ho
    Correspondence
    Correspondence to: Sunita P. Ho, 707 Parnassus Avenue, D 3212, UCSF, San Francisco, CA 94143, China.
    Affiliations
    Division of Preclinical Education, Biomaterials & Engineering, School of Dentistry, University of California San Francisco, San Francisco, CA, 94143, USA

    Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, 94143, USA
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  • Author Footnotes
    1 both authors contributed equally and are the first authors.
Published:November 20, 2020DOI:https://doi.org/10.1016/j.jpurol.2020.11.023

      Summary

      Objective

      Calcium oxalate stones are the most common type among stone-forming patients and in some cases result from predisposed genetic conditions. In this work, we examined the differences in structure and chemical composition between oxalate stones from patients from three groups: 1) pediatric patients that were genetically predisposed (primary hyperoxaluria) to form stones (PPH); 2) control pediatric patients that did not have such genetic predisposition (PN-PH); 3) adult patients that formed oxalate stones without the genetic predisposition (A-CaOx). A variety of instrumental analyses were conducted to identify physicochemical properties of stones characteristic of predisposed pediatric (PPH), pediatric hyperoxaluria (PN-PH), and adult (A-CaOx) patient populations.

      Methods

      Genetic variants of 16 stone-forming patients were determined using whole-exome gene sequencing. Components of stones from PPH (n = 6), PN-PH (n = 5), and A-CaOx (n = 5) groups were identified using Fourier transform infrared (FTIR) spectroscopy. Stone morphology and density were evaluated using high resolution X-ray computed tomography (micro-XCT). Stone microstructure and elemental composition were mapped with scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, respectively.

      Results

      Calcium oxalate bipyramidal crystals were found on stones from all groups. Stones from PPH patients with PH types I and II were composed of calcium oxalate monohydrate (COM) with relatively uniform mineral density (1224 ± 277 mg/cc) and distinct smooth surfaces. By contrast, micro-spherical calcium phosphate particles were found only on PN-PH stones, which also showed a broader range of mineral densities (1266 ± 342 mg/cc). Stones from the PN-PH group also contained phosphorus (P), which was absent in NP-PH stones. A-CaOx stones were of significantly lower mineral density (645 ± 237 mg/cc) than pediatric stones and were more heterogeneous in their elemental composition.

      Conclusion

      Summary Figure
      Graphical AbstractStructure and elemental composition of pediatric primary hyperoxaluria (PPH), pediatric without primary hyperoxaluria (PN-PH), and adult calcium oxalate (A-CaOx) stones.

      Keywords

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