Abstract: TH-PO1092
Renal Arterial Hyalinosis Predicts Cardiovascular Events in IgAN: Proteomics-Guided Identification of Annexin A1 as a Molecular Link
Session Information
- Pathology and Lab Medicine
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
- Cheng, Hong, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China
- Chen, Feifei, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China
- Wang, Guoqin, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China
- Ye, Nan, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China
Background
Patients with IgA nephropathy (IgAN) face a significantly elevated risk of cardiovascular events. While renal arteriolosclerosis is a common histological finding in these patients, the differential prognostic impact of its distinct phenotypes—arterial hyalinosis and intimal thickening —on major adverse cardiovascular events (MACE) remains poorly understood. This study aimed to distinguish the prognostic roles of these specific vascular lesions and identify underlying molecular correlates using a proteomic approach.
Methods
This study employed a three-stage design: (1) Clinical Discovery (n=614): A prospective cohort of biopsy-proven IgAN patients was evaluated to determine the association of arteriolosclerosis with MACE using multivariable Cox models. (2) Proteomic Exploration (n=8): High-resolution LC-MS/MS was performed on renal biopsy tissues using extreme-phenotype sampling (severe hyalinosis vs. no hyalinosis). (3) Validation (n=80): Assessment of circulating ANXA1 levels and their association with cardiovascular outcomes. MACE was defined as a composite of cardiovascular death, non-fatal myocardial infarction, and stroke.
Results
In the clinical cohort, arterial hyalinosis independently predicted MACE in fully adjusted multivariable Cox models (HR 2.00, 95% CI 1.14-3.52, P=0.015). In contrast, intimal thickening was not significantly associated with cardiovascular risk after adjusting for clinical covariates. Proteomic profiling identified Annexin A1 (ANXA1) as a significant differentially expressed protein in patients with arterial hyalinosis (q < 0.050), which was associated with pathways involving endothelial injury. In the validation subset, circulating ANXA1 levels were significantly higher in patients with arterial hyalinosis (P<0.001). While higher circulating ANXA1 was associated with MACE risk in baseline models (HR 2.23, P=0.028), the association was attenuated after adjusting for arterial hyalinosis status (HR 2.14, P=0.040), identifying circulating ANXA1 as a non-invasive marker for the structural burden of hyaline arteriolosclerosis.
Conclusion
Renal arterial hyalinosis is a specific histology-based predictor of cardiovascular events in IgA nephropathy. ANXA1 represents a measurable molecular correlate of arterial hyalinosis that may serve as a potential biomarker for cardio-renal risk stratification.