Abstract: FR-PO1171
Metabolomic Biomarkers for Predicting Kidney Prognosis in CKD
Session Information
- CKD: Screening, Diagnosis, Serum and Urine Biomarkers, and Scoring Indices
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Kinomura, Sosuke, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Toyohara, Takafumi, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Noguchi, Yuji, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Watanabe, Shun, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Kujirai, Ryota, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Goto, Sawako, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Kikuchi, Koichi, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Suzuki, Takehiro, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Soga, Tomoyoshi, Keio Gijuku Daigaku, Minato, Tokyo, Japan
- Tanaka, Tetsuhiro, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
- Abe, Takaaki, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan
Background
Nephrosclerosis is increasingly prevalent, particularly in aging populations. Unlike glomerular diseases, it is typically characterized by minimal urinary abnormalities, preventing early diagnosis and prognostic assessment. We conducted a comprehensive metabolomic analysis to identify potential prognostic biomarkers for nephrosclerosis.
Methods
We retrospectively analyzed 56 patients with CKD stage G2–G3 followed in our nephrology and hypertension outpatient clinic. Baseline plasma samples underwent untargeted quantitative metabolomics, covering about 510 metabolites. Longitudinal clinical data were collected over up to 3 years (2021–2024). Logistic regression assessed associations between each metabolite and renal prognosis, defined by dichotomizing the slope of eGFR decline into favorable and unfavorable outcome groups. To examine pathophysiological significance of candidate biomarkers, we subsequently performed functional evaluation using a CKD mouse model.
Results
Several metabolites were significantly associated with renal prognosis, including indoxyl sulfate and symmetric dimethylarginine, both known uremic toxins. Notably, trans-aconitate (TAA), a tricarboxylic acid cycle–related intermediate, emerged as a novel candidate associated with adverse renal outcomes. In an adenine-induced CKD mouse model, administration of TAA resulted in significantly elevated serum creatinine and urea levels. While previous studies have only reported blood pressure elevation caused by TAA administration, this is the first report of its association with renal function decline.
Conclusion
We identified TAA as a novel metabolite associated with poor renal prognosis in nephrosclerosis. This association was further supported by in vivo experiments. These findings suggest that TAA may be involved in CKD progression and has potential as a prognostic biomarker. Our results are helpful for early risk stratification and therapeutic decision-making in nephrosclerosis. Further validation in independent patient cohorts and mechanistic studies is warranted to clarify its biological function and the clinical relevance of TAA.
Funding
- Government Support – Non-U.S.