Abstract: SA-PO754
Association of Urinary Adhesion Molecules Derived from Endothelial Cells and Kidney Pathology in ANCA-Associated Glomerulonephritis
Session Information
- ANCA-Associated Vasculitis, Anti-GBM Disease, and Other RPGN
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Tanaka, Tomoki, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Umeda, Ryosuke, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Minatoguchi, Shun, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Usui, Joichi, Tsukuba Daigaku Igaku Iryokei, Tsukuba, Ibaraki, Japan
- Yamagata, Kunihiro, Tsukuba Daigaku Igaku Iryokei, Tsukuba, Ibaraki, Japan
- Hasegawa, Midori, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Tsuboi, Naotake, Fujita Ika Daigaku, Toyoake, Aichi, Japan
Background
Although renal biopsy provides valuable histological information, it is an invasive procedure carrying a risk of bleeding in patients with ANCA-associated glomerulonephritis (ANCA-GN). Therefore, non-invasive urinary biomarkers reflecting renal pathology are highly desirable. ICAM-1 and VCAM-1 belong to the immunoglobulin superfamily serving as cell adhesion molecules and their expression on the cell surface is induced in response to inflammatory stimuli. The aim of the current study is to evaluate the clinical significance of ICAM-1 and VCAM-1 as urinary biomarkers in relation to the pathological findings in ANCA-GN.
Methods
The Japanese nationwide cohort (RemIT-JAV-RPGN cohort, n = 44) and our institutional cohort (FHU cohort, n = 76) for ANCA-GN were subjected to the current study. Urinary concentrations of soluble ICAM-1 and VCAM-1 measured by ELISA were standardized with urinary creatinine (UICR or UVCR), and urine VCAM-1 to ICAM-1 ratio (UVIR) was also obtained. We investigated the association of both biomarkers with renal pathology.
Results
In the RemIT-JAV-RPGN cohort, a correlation between UVIR and the severity of interstitial fibrosis and tubular atrophy (IF/TA) was observed, and similar associations for both UVCR and UVIR were also observed in the FHU cohort. Furthermore, UVIR was found to be a superior indicator for assessing the severity of IF/TA compared with UVCR. In the FHU cohort, when categorizing interstitial damages to interstitial inflammatory cell infiltration (ICI) and interstitial fibrosis (IF), UVIR was consistently increased according to the severity of ICI, but not to IF. Association of urine ICAM-1 or VCAM-1 with cellular crescents was not observed in either cohort. ROC analysis demonstrated that UVIR has superior predictive ability for IF/TA ≥25% in both cohorts. Although the predictive performance of UVIR was comparable to that of urine α1-microglobulin to creatinine ratio (Uα1MGCR) in the FHU cohort, multivariate ROC analysis of UVIR combined with Uα1MGCR improved the prediction ability compared to Uα1MGCR alone.
Conclusion
The urinary ICAM-1 and VCAM-1 are reliable biomarkers that reflect renal pathological activity related to acute interstitial inflammation in ANCA-GN.
Funding
- Commercial Support – Bayer Yakuhin, Ltd, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Sumitomo Pharma Co., Ltd.