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A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

Author

Listed:
  • Victor Hugo Canela

    (Indiana University School of Medicine)

  • William S. Bowen

    (Indiana University School of Medicine)

  • Ricardo Melo Ferreira

    (Indiana University School of Medicine)

  • Farooq Syed

    (Indiana University School of Medicine)

  • James E. Lingeman

    (Indiana University School of Medicine)

  • Angela R. Sabo

    (Indiana University School of Medicine
    Indiana University School of Medicine)

  • Daria Barwinska

    (Indiana University School of Medicine)

  • Seth Winfree

    (Indiana University School of Medicine
    University of Nebraska Medical Center)

  • Blue B. Lake

    (San Diego Institute of Science, Altos Labs)

  • Ying-Hua Cheng

    (Indiana University School of Medicine)

  • Joseph P. Gaut

    (Washington University)

  • Michael Ferkowicz

    (Indiana University School of Medicine)

  • Kaice A. LaFavers

    (Indiana University School of Medicine)

  • Kun Zhang

    (San Diego Institute of Science, Altos Labs)

  • Fredric L. Coe

    (University of Chicago)

  • Elaine Worcester

    (University of Chicago)

  • Sanjay Jain

    (Washington University)

  • Michael T. Eadon

    (Indiana University School of Medicine
    Indiana University School of Medicine)

  • James C. Williams

    (Indiana University School of Medicine)

  • Tarek M. El-Achkar

    (Indiana University School of Medicine
    Indiana University School of Medicine
    Indianapolis VA Medical Center)

Abstract

Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.

Suggested Citation

  • Victor Hugo Canela & William S. Bowen & Ricardo Melo Ferreira & Farooq Syed & James E. Lingeman & Angela R. Sabo & Daria Barwinska & Seth Winfree & Blue B. Lake & Ying-Hua Cheng & Joseph P. Gaut & Mic, 2023. "A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38975-8
    DOI: 10.1038/s41467-023-38975-8
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    References listed on IDEAS

    as
    1. Blue B. Lake & Song Chen & Masato Hoshi & Nongluk Plongthongkum & Diane Salamon & Amanda Knoten & Anitha Vijayan & Ramakrishna Venkatesh & Eric H. Kim & Derek Gao & Joseph Gaut & Kun Zhang & Sanjay Ja, 2019. "A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    2. Vijay Saxena & Hongyu Gao & Samuel Arregui & Amy Zollman & Malgorzata Maria Kamocka & Xiaoling Xuei & Patrick McGuire & Michael Hutchens & Takashi Hato & David S. Hains & Andrew L. Schwaderer, 2021. "Kidney intercalated cells are phagocytic and acidify internalized uropathogenic Escherichia coli," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
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