Kidney Week

Abstract: TH-PO0356

ADAMTS13 Preserves Kidney Function in Alport Syndrome

Session Information

• Glomerular Diseases: Genetics to Therapeutics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Soloyan, Hasmik, Children's Hospital Los Angeles, Los Angeles, California, United States

Hasmik Soloyan, MD

• Chomoyan, Hripsime, Children's Hospital Los Angeles, Los Angeles, California, United States

Hripsime Chomoyan

• De Filippo, Roger E., Children's Hospital Los Angeles, Los Angeles, California, United States

Roger E. De Filippo, MD

• Perin, Laura, Children's Hospital Los Angeles, Los Angeles, California, United States

Laura Perin, PhD

• Sedrakyan, Sargis, Children's Hospital Los Angeles, Los Angeles, California, United States

Sargis Sedrakyan, PhD

Background

Alport syndrome (AS) is a hereditary chronic kidney disease caused by mutations in type IV collagen genes that lead to progressive renal failure with limited therapeutic options. While pathogenesis has focused on podocyte injury, emerging evidence identifies glomerular endothelial cells (GECs) as early and critical targets. In AS, GECs display lipid accumulation, mitochondrial dysfunction, inflammatory activation, and microthrombus formation, resulting in impaired glomerular microcirculation. We and others observed downregulation of ADAMTS13, a von Willebrand factor–cleaving protease regulating endothelial homeostasis and thrombosis, in AS models and human biopsies. Here, we investigate whether lipid metabolic alterations drive ADAMTS13 downregulation and whether its restoration can preserve glomerular microvascular integrity and slow disease progression.

Methods

In vitro, silencing experiments on primary human GEC were performed to study the role of fatty acid metabolism on ADAMTS13 expression. Endothelial activation markers (VCAM-1, ICAM-1) were assessed by immunoblotting and ELISA. In vivo, Col4a5-/- Alport mice received biweekly intravenous recombinant ADAMTS13, followed by assessment of albuminuria and renal injury.

Results

ADAMTS13 expression was significantly reduced in Col4a5-/- glomeruli at moderate disease stages. Disruption of lipid metabolism via FASN suppression led to marked downregulation of ADAMTS13 in GECs, supporting a direct metabolic regulatory mechanism. ADAMTS13 knockdown induced endothelial activation, evidenced by increased VCAM-1 and ICAM-1 levels. Therapeutic administration of recombinant ADAMTS13 in Alport mice significantly reduced proteinuria and improved kidney function.

Conclusion

These findings define a lipid metabolism–ADAMTS13 axis linking GEC dysfunction to microvascular injury in AS. Loss of ADAMTS13 promotes endothelial activation, inflammation, and microthrombi formation, contributing to disease progression. Restoration of ADAMTS13 preserves glomerular microvascular integrity and represents a promising therapeutic strategy for AS and potentially other proteinuric CKD characterized by endothelial dysfunction. Notably, these findings support a paradigm shift toward endothelial-centered mechanisms in Alport syndrome and highlight a clinically translatable strategy, as ADAMTS13 is an established therapeutic with potential for rapid repurposing in kidney disease.