Kidney Week

Abstract: TH-PO0291

Single-Cell Multiomic Characterization Reveals Endothelial Remodeling-Fibrosis Trajectory in Kidney Biopsy Samples of Patients with Malignant Hypertension

Session Information

• Hypertension and CVD: Mechanisms
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Ma, Yixin, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Yixin Ma

• Xu, Lubin, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Lubin Xu, MD

• Huang, Zheng, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Zheng Huang

• Yin, Saifu, Department of Urology/Kidney Transplantation Center, West China Hospital, Sichuan University, Beijing, China

Saifu Yin, PhD

• Li, Yun, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Yun Li

• Zhang, Guoqing, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China

Guoqing Zhang

• Cao, Shilu, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Shilu Cao

• Hu, Yuting, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Yuting Hu, MS

• Lin, Yitao, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Yitao Lin

• Zhu, Jiahao, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Jiahao Zhu

• Lin, Tao, Department of Urology/Kidney Transplantation Center, West China Hospital, Sichuan University, Beijing, China

Tao Lin, MD, PhD

• Jiang, Lan, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

Lan Jiang

• Chen, Limeng, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Limeng Chen, MD, PhD

Background

Renal endothelial cells (ECs) exhibit significant heterogeneity and remarkable plasticity in various physiological and pathological conditions. Malignant hypertension (mHTN), predominantly affecting young males, is characterized by thrombotic microangiopathy (TMA) in renal pathology, reflecting extensive endothelial injury. However, the precise cellular responses of renal ECs during mHTN remain poorly understood.

Methods

We collected the renal biopsy samples of nine mHTN patients, ten patients with benign hypertension (BHT), and nineteen healthy transplantation donors at the zero hour of surgery. UDA-seq (Universal Droplet Microfluidics-Based Combinatorial Indexing for Massive-Scale Multimodal Single-cell Sequencing) technology was applied for single-nucleus RNA sequencing (snRNAseq) and ATAC sequencing (snATACseq) of renal biopsy specimens.

Results

Different from the BHT patients, the mHTN patients were young males (88.9%) with an average eGFR of 31 mL/min/1.73m². In the vascular interstitial compartment including endothelial cells, vascular smooth muscle cells/pericytes and fibroblasts, up-regulated genes in mHTN patients were enriched in pathways such as extracellular matrix organization, vascular development and angiogenesis regulation. Subclustering of peritubular capillary endothelial cells (EC-PTCs) yielded 8 clusters, where subclusters 4 and 5 were underrepresented in healthy controls (<25%). Among these disease-enriched cell clusters, subcluster 4 expressing a high fetal kidney endothelial cell signature was defined as “remodeling” EC-PTCs and subcluster 5 expressing profibrotic marker ACKR1 and VCAM1 was defined as “fibrotic”. Pseudotime trajectory analysis from normal to profibrotic cell subclusters identified key transcriptional factors including an endothelial lineage determining factor ETV2, endothelial-to-mesenchymal transition-related factor SOX9 and oxidative stress-responsive factor BACH1.

Conclusion

We are the first to report the single ECs-based pathophysiology process, injury trajectory from remodeling to fibrosis, with prioritized transcriptional factors in mHTN patients, which sheds light on the future precision medication.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025wx5p7p4f