Abstract: SA-PO1034
MUC1 on Urinary Extracellular Vesicles for Detection of Impaired Renal Function
Session Information
- Pathology and Lab Medicine - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Takizawa, Keiichi, Tokyo Daigaku, Bunkyo-ku, Tokyo, Japan
- Nishimura, Tatsuya, Tokyo Daigaku, Bunkyo-ku, Tokyo, Japan
- Harita, Yutaka, Tokyo Daigaku, Bunkyo-ku, Tokyo, Japan
Background
The nephron's various cell types produce urinary extracellular vesicles (uEVs), which have the potential as a promising biomarker resource. Aiming to detect chronic kidney disease (CKD) in its early stage, we performed proteome analysis of uEVs from patients with a congenitally reduced number of functional nephrons and found that pediatric CKD can be detected accurately by the expression levels of molecules such as MUC1 in uEVs (iScience, 2022). In this study, we validated the diagnostic capacity of an ELISA-based test method analyzing uEVs to separate adult individuals with decreased renal function in a Japanese community cohort of the Tohoku Medical Megabank Project.
Methods
Two hundred eleven samples (male 109, female 102) provided were analyzed. The mean age ± SD was 51.2 ± 14.7 years. The expression levels of MUC1 and CD9, a classical exosomal marker, on the surface of uEVs (uEVs_MUC1 and uEVs_CD9) were measured using ELISA plates that enabled the isolation of uEVs and quantitation of expression of molecules. The correlation between the expression levels and clinical parameters was analyzed.
Results
uEVs_MUC1 showed a positive correlation with uEVs_CD9 but not with urinary albumin. As in pediatric patients with kidney diseases, the expression of uEVs_MUC1 was significantly decreased in adult individuals with reduced renal function (eGFR <60 ml/min/1.73m2) (P < 0.001). uEVs_MUC1 had an AUC of 0.88 for separating individuals with eGFR <45 from those with eGFR ≥45 and 0.92 for separating those with eGFR <30 from those with eGFR ≥30. When combined with urinary albumin, the diagnostic accuracy was further enhanced. To further apply this ELISA to clinical testing, we generated a high-titer monoclonal antibody against MUC1, and established a protocol to quantify uEVs_MUC1 in clinical samples.
Conclusion
MUC1 expression in uEVs can be a biomarker of renal dysfunction independent from proteinuria, which was validated in childhood and adult cohorts. Future research will focus on elucidating the mechanism and conducting prospective investigations in order to advance with the development of the uEVs-based noninvasive test technique robustly diagnostic for CKD.
Funding
- Other NIH Support