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

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, Michael Ferkowicz, Kaice A. LaFavers, Kun Zhang, Fredric L. Coe, Elaine Worcester, Sanjay Jain (), Michael T. Eadon (), James C. Williams () and Tarek M. El-Achkar ()
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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
Daria Barwinska: Indiana University School of Medicine
Seth Winfree: Indiana University School of Medicine
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
James C. Williams: Indiana University School of Medicine
Tarek M. El-Achkar: Indiana University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38975-8

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