Kidney Week

Abstract: FR-PO0258

Metabolomic Biomarkers for Predicting Kidney Prognosis in Hypertension-Associated CKD and Evaluation of Their Toxicity in a Kidney Failure Model

Session Information

• CKD: Omics, Systemic Stressors, and Targeted Pharmacotherapy
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2201 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Kinomura, Sosuke, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Sosuke Kinomura, MD

• Watanabe, Shun, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Shun Watanabe, MD, PhD

• Noguchi, Yuji, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Yuji Noguchi, MD

• Kujirai, Ryota, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Ryota Kujirai, PhD

• Goto, Sawako, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Sawako Goto, MD, PhD

• Kikuchi, Koichi, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Koichi Kikuchi, MD, PhD

• Suzuki, Chitose, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Chitose Suzuki

• Suzuki, Takehiro, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Takehiro Suzuki, MD, PhD

• Soga, Tomoyoshi, Keio Gijuku Daigaku, Minato, Tokyo, Japan

Tomoyoshi Soga, PhD

• Tanaka, Tetsuhiro, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Tetsuhiro Tanaka, MD, PhD, FASN

• Abe, Takaaki, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Takaaki Abe, MD, PhD

• Toyohara, Takafumi, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan

Takafumi Toyohara, MD, PhD

Background

Hypertension-associated chronic kidney disease (CKD) is a growing clinical problem, but its prognostic markers remain less well established than those for diabetic kidney disease. Previous metabolomic studies on hypertension-associated CKD remain limited. This study aimed to identify metabolites predictive of renal outcomes in hypertension-associated CKD and to evaluate their effects in a renal failure model.

Methods

We enrolled 56 patients with CKD stage G2–G3 followed at our nephrology and hypertension outpatient clinic. Longitudinal clinical data were collected for up to 3 years (2021–2024), and 510 metabolites at baseline were analyzed using targeted quantitative metabolomics. The association between each metabolite and eGFR slope was analyzed using logistic regression. The effects of candidate metabolites on renal function were evaluated using an adenine-induced CKD mouse model.

Results

Using logistic regression, indoxyl sulfate, trans-aconitate (TAA), SDMA, creatinine, and p-cresyl sulfate were associated with eGFR decline. Among these, indoxyl sulfate was the top-ranked metabolite associated with adverse renal outcomes, consistent with previous reports. TAA was the second-ranked metabolite (OR 4.06, 95% CI 1.42–15.37, p=0.019). TAA is an isomer of cis-aconitate and has been reported to inhibit aconitase activity, potentially impairing TCA cycle activity and mitochondrial respiration. To examine the effects of TAA on renal function in renal failure, we administered TAA to mice with adenine-induced renal failure. Adenine-induced renal dysfunction was exacerbated by TAA treatment. The levels of TMAO, a uremic toxin, and 1-methyladenosine, a marker of oxidative stress, were increased compared with renal failure alone. In addition, TAA decreased the cis-to-trans-aconitate ratio, indicating an imbalance in aconitate metabolism associated with impaired aconitase activity and reduced TCA cycle function. Furthermore, decreased isocitrate levels in TAA-treated mice suggested reduced TCA cycle activity, which may contribute to renal dysfunction.

Conclusion

TAA is a prognostic marker for renal outcomes in hypertension-associated CKD and a novel metabolite that may contribute to renal dysfunction by impairing the TCA cycle. Therefore, TAA-lowering interventions may be a potential therapeutic strategy for hypertension-associated CKD.