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Kidney Week

Abstract: TH-PO1110

Single-Nucleus RNA Sequencing of AKI to CKD Transition: Novel Perspectives on Leptospirosis Kidney Disease

Session Information

  • CKD: Mechanisms - 1
    October 24, 2024 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Lu, Yuehan, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • Chou, Li-Fang, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • Yang, Huang-Yu, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • Yang, Chih-Wei, Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Background

Leptospirosis is a widespread zoonotic disease. Prior cohort studies highlight that acute Leptospira infection leads to chronic kidney disease(CKD). This study investigates the transition from acute kidney injury (AKI) to CKD due to Leptospira infection.

Methods

1.Mouse model for leptospiral kidney disease. 2.Transcriptome-wide changes and single-nucleus RNA sequencing(snRNA-seq) in infected kidneys.

Results

The study examined the pathogenic mechanisms from acute to chronic phases during leptospirosis progression. Infected mice showed kidney injury and bacterial adherence to the renal tubules by day 28 post-infection. Renal pathology revealed tubular degeneration, inflammation, and fibrosis characteristic of CKD. Transcriptome profiling identified 714 and 1089 differentially expressed genes at days 7 and 28 postinfection, respectively, which enriched in pathways related to cell activation and innate immune response. Hierarchical clustering identified immune-related genes like LBP, FCGR1, SYK, IL33, COLLA1, IRF7, NCF1, and TLR2, highlighting roles in immune response regulation and fibrogenesis. SnRNA-seq characterized renal cell states to identify 33 distinct clusters, including various renal cell types. Normal proximal tubular cells (PTCs) decreased on the 7th day postinfection, with an increment of injured PTCs with a potential marker Kynu. Initially, fibroblast numbers increased in the infected group, suggesting early fibrosis development. By day 28, immune cell populations grew, indicating their role in chronic Leptospira kidney disease.

Conclusion

Leptospira infection disrupts normal kidney cell composition, particularly affecting proximal tubules. Early infection stages revealed a rise in fibroblasts. As infection progresses, immune cell populations increase, indicating their involvement in CKD pathophysiology.

UMAP visualization by experimental condition

Funding

  • Government Support – Non-U.S.