Abstract: TH-PO0096
Development of a Novel Diagnostic Method for Atypical Hemolytic Uremic Syndrome Using Extracellular Vesicles
Session Information
- AKI: Pathogenesis and Disease Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Matsuyama, Tetsuya, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan
- Kato, Noritoshi, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan
- Noda, Yuhei, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan
- Kosugi, Tomoki, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan
- Maruyama, Shoichi, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan
Background
Atypical hemolytic uremic syndrome (aHUS) is a group of disorders characterized by thrombotic microangiopathy (TMA). It is known that aberrant activation of the alternative complement pathway plays a key role in the pathogenesis of aHUS. Although the prognosis of aHUS has improved with the advent of anti-C5 antibody, differentiating TMA subtypes remains challenging, particularly distinguishing aHUS from secondary TMA. To make a differential diagnosis, previous studies have focused on complement activation in the liquid phase, no definitive conclusions have been reached.
In this study, we focused on the hypothesis that complement activation occurs on the cell membrane in aHUS. We investigated whether measuring complement activation products on small extracellular vesicles (sEVs) could serve as a diagnostic approach for aHUS.
Methods
Plasma samples from patients registered in the Japanese nationwide aHUS registry between January 2020 and December 2022, diagnosed with TMA, were included in this study. Among 244 samples, 40 cases (15 with aHUS and 25 with secondary TMA) that met the inclusion criteria were selected.
sEVs were isolated by ultracentrifugation, C3b and C5b-9 levels in both plasma and sEVs were quantified by ELISA.
Results
Both plasma and sEV samples showed significantly higher C3b levels in the aHUS compared to the secondary TMA (sEVs: p<0.0001, plasma: p<0.01). Furthermore, ROC analysis suggested that C3b measurement in sEVs was more useful as a diagnostic test compared to plasma (sEVs: AUC 0.821, plasma: AUC 0.661). On the other hand, C5b-9 levels didn’t differ in both groups.
Conclusion
The measurement of C3b levels in sEVs may be useful for distinguishing between aHUS and secondary TMA.