Presented by: Heiko Yang MD, PhD
UCSF

Introduction

We recently identified an embryonically derived tissue resident subpopulation of macrophages associated with Randall’s plaques. These macrophages typically reside in the renal cortex in normal kidneys, so how they arrive at the papillary tip in stone formers is unclear. The objective of this study was to use our single nuclear RNA sequencing dataset to identify which cells at the papillary tip may be responsible for chemokine signaling to these macrophages.

Materials

Randall’s plaque and renal papillary tissues were collected from adult patients undergoing stone surgery. Randall’s plaque tissue was obtained from endoscopic biopsies while whole renal papilla tissue were obtained from fresh nephrectomy specimens. Single nuclear RNA sequencing was performed using the 10X Genomics platform and Illumina NovaSeq S4. Additional tissue was saved for immunohistologic staining. Analysis was conducted using R Studio and Seurat. Intercellular molecular interactions were predicted using CellphoneDB.

Results

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CXCR4-mediated chemokine signaling was found originating from epithelial cells in the loop of Henle. This interaction was highly specific to RP-associated macrophages and was not predicted to originate from other epithelial or stromal cell types. Adhesion interactions via P-selectin and E-selectin were notably absent between vascular endothelial cells and RP-associated macrophages, reinforcing a non-hematologic origin.  

Conclusion

Epithelial cells at the loop of Henle may be responsible for attracting RP-associated macrophages to the papillary tip. While the role of these macrophages in biomineralization is still being investigated, these results support the hypothesis that the loop of Henle is the functional location of Randall’s plaque pathology.

Funding

California Urology Foundation (HY), Program in Biomineralization Studies (SH)

Co-Authors

Hanbing Song, PhD
UCSF

Thomas Chi, MD, MBA
UCSF

Marshall Stoller, MD
UCSF

Franklin Huang, MD, PhD
UCSF

Sunita Ho, PhD
UCSF