Abstract: TH-PO992
Gut Microbe-Derived Metabolite Trimethylamine N-oxide and Risk of CKD Progression
Session Information
- CKD: Epidemiology, Risk Factors, and Prevention - 1
October 24, 2024 | 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
- Cheng, Evelyn, University of Washington, Seattle, Washington, United States
- Lin, Ting-yun, Taipei Tzu Chi Hospital, Taipei, Taiwan
- Hung, Szu-Chun, Taipei Tzu Chi Hospital, Taipei, Taiwan
Background
Trimethylamine N-oxide (TMAO) is derived from gut microbial metabolism of dietary L-carnitine, phosphatidylcholine, and choline. Higher TMAO have been associated with increased risk of cardiovascular diseases. However, the potential relevance between TMAO and kidney function decline in patients with CKD remains unclear.
Methods
We prospectively followed 152 participants with CKD stages 3–5. Measurement of plasma TMAO was done by liquid chromatography-mass spectrometry at baseline. The primary outcome was defined as a composite of progression of kidney disease (sustained decline in eGFR of ≥40% from baseline, initiation of dialysis, or death from renal causes). Additionally, we performed logistic regression to determine the probability of slow and fast eGFR decline (≤3 versus >3 ml/min/year) with plasma TMAO as the main predictor.
Results
Participants with higher TMAO were more likely to have a significantly lower eGFR. Higher TMAO was significantly associated with an increased risk of the composite outcome after adjustment for demographics, comorbidities, proteinuria, and the use of ACEI/ARB (hazard ratio, 1.48; 95% CI, 1.21–1.97). However, the association was attenuated and statistically insignificant after adjustment for eGFR. Higher TMAO was significantly associated with increased odds of fast eGFR decline after adjustment for eGFR, proteinuria, and other confounding characteristics (odds ratio, 2.35; 95% CI, 1.31–4.22). In addition, gut microbial analyses showed that compared to slow eGFR decliners, fast eGFR decliners had a significantly higher abundance of Ruminococcus and Collinsella, which have been implicated as TMA-producing bacteria in previous studies.
Conclusion
TMAO is associated with fast eGFR decline in patients with CKD. Whether the gut microbiota contributes to the progression of CKD needs further investigations.
Cox proportional hazard survival analysis
| Model 1 | Model 2 | Model 3 | ||||
| HR (95% Cl) | P value | HR (95% Cl) | P value | HR (95% Cl) | P value | |
| TMAO | 1.74 (1.37-2.21) | <0.001 | 1.48 (1.12-1.97) | 0.007 | 1.18 (0.86-1.63) | 0.306 |
HR per 1-SD increase. Model 1 adjusted for age and sex. Model 2 additionally adjusted for DM, use of ACEI/ARB, BMI, urine protein, and phosphate. Model 3 additionally adjusted for eGFR.
Higher abundance of Ruminococcus and Collinsella (fast vs. slow eGFR decliners)