Kidney Week

Abstract: FR-PO934

Associations of Plasma Trimethylamine N-Oxide-Related Metabolites with the Development and Progression of Albuminuria

Session Information

• CKD Epidemiology, Risk Factors, Prevention - II
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Wang, Meng, Tufts University, Boston, Massachusetts, United States

Meng Wang,

• Tang, W.H. Wilson, Cleveland Clinic, Cleveland, Ohio, United States

W.H. Wilson Tang,

• Li, Xinmin S., Cleveland Clinic, Cleveland, Ohio, United States

Xinmin S. Li,

• De Oliveira Otto, Marcia C., The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas, United States

Marcia C. De Oliveira Otto,

• Lemaitre, Rozenn, University of Washington, Seattle, Washington, United States

Rozenn Lemaitre,

• Fretts, Amanda M., University of Washington, Seattle, Washington, United States

Amanda M. Fretts,

• Nemet, Ina, Cleveland Clinic, Cleveland, Ohio, United States

Ina Nemet,

• Sotoodehnia, Nona, University of Washington, Seattle, Washington, United States

Nona Sotoodehnia,

• Budoff, Matthew Jay, The Lundquist Institute, Torrance, California, United States

Matthew Jay Budoff,

• Didonato, Joseph A., Cleveland Clinic, Cleveland, Ohio, United States

Joseph A. Didonato,

• Wang, Zeneng, Cleveland Clinic, Cleveland, Ohio, United States

Zeneng Wang,

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak,

• Mozaffarian, Dariush, Tufts University, Boston, Massachusetts, United States

Dariush Mozaffarian,

• Hazen, Stanley L., Cleveland Clinic, Cleveland, Ohio, United States

Stanley L. Hazen,

Background

Trimethylamine N-oxide (TMAO) is a gut-microbiota generated metabolite of dietary choline and carnitine. In animal models, TMAO increases albuminuria, an early, sensitive marker of kidney damage. Yet, little is known about TMAO and albuminuria in humans. We investigated prospective associations of plasma TMAO and its two microbiome-derived intermediates, crotonobetaine and γ-butyrobetaine, with the development and progression of albuminuria.

Methods

We included 6,101 US adults with normal (<30mg/g) baseline urine albumin to creatinine ratio (ACR) from the Multi-ethnic Study of Atherosclerosis, a community-based cohort. TMAO-related metabolites were measured using mass spectrometry at baseline and year 5. ACR levels were measured up to 4 times during follow-up. Time-varying Cox models related serial TMAO measures to elevated albuminuria, defined as the first occurrence of ACR ≥ 30 mg/g, adjusting for sociodemographic, lifestyle, diet, and CVD risk factors. Linear mixed models related serial TMAO measures to annualized ACR changes in 6,319 participants with at least one follow-up ACR measure (no exclusions for baseline ACR levels), adjusting for baseline ACR and other covariates.

Results

During a median follow-up of 16 years, 995 participants developed elevated albuminuria. Higher levels of TMAO and crotonobetaine, but not γ-butyrobetaine, associated with higher risk of elevated albuminuria (Figure). All three metabolites positively associated with annualized ACR increase (5^th vs. 1^st quintile [95%CI] =3.54 [1.10, 5.98], 4.28 [1.89, 6.67], and 4.49 [1.36, 7.61] mg/g per year, respectively).

Conclusion

In a multi-ethnic, community-based cohort of US adults, higher levels of gut microbiota-generated TMAO-related metabolites were associated with elevated albuminuria and its progression.

Multivariable-adjusted relationship of plasma levels of TMAO (left), crotonobetaine (middle), and γ-butyrobetaine (right) with the risk of elevated albuminuria

Funding

• Private Foundation Support