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Abstract: SA-PO931

Metabolomics of Uremic Symptoms in CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

  • Wulczyn, Kendra E., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Srivastava, Anand, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • He, Jiang, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
  • Kelly, Tanika, Tulane University, New Orleans, Louisiana, United States
  • Ricardo, Ana C., University of Illinois Chicago, Chicago, Illinois, United States
  • Shah, Vallabh O., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Nelson, Robert G., National Institutes of Health, Bethesda, Maryland, United States
  • Hsu, Chi-yuan, University of California San Francisco, San Francisco, California, United States
  • Anderson, Amanda Hyre, Tulane University, New Orleans, Louisiana, United States
  • Denburg, Michelle, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Ramachandran, Vasan S., Boston University School of Medicine, Boston, Massachusetts, United States
  • Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Clish, Clary B., Broad Institute, Cambridge, Massachusetts, United States
  • Ouyang, Tianqi, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Rincon-Choles, Hernan, Cleveland Clinic, Cleveland, Ohio, United States
  • Mehta, Rupal, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Shafi, Tariq, The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States

Group or Team Name

  • CKD Biomarkers Consortium
Background

The disrupted metabolic pathways causing uremic symptoms are not known. We utilized untargeted metabolomics to identify potential metabolite markers of uremic symptoms in patients with CKD.

Methods

We measured 540 plasma metabolites in 1,766 randomly selected CRIC Study participants at the Year-1 visit and examined their association with uremic symptoms, assessed concurrently using the KDQOL-36 instrument. Metabolites significantly associated with symptoms were identified in cross-sectional analyses using multivariable adjusted linear regression with Bonferroni correction. Then, a parsimonious metabolite profile for each symptom was investigated using LASSO regression.

Results

The mean eGFR of participants was 42 mL/min/1.73 m2. The most prevalent symptoms were pain (56%), fatigue (54%), paresthesia (46%), and pruritus (45%); nausea (29%) and anorexia (22%) were less common. Regression models identified several metabolites significantly associated with uremic symptoms (Table). Only xenobiotic metabolites were significantly associated with fatigue and paresthesia in both regression models. Notably, higher levels of dimethylguanidino valerate, a metabolite associated with cardiovascular risk, was associated with increased pruritus and nausea severity, and higher levels of N4-acetylcytidine, a potential uremic toxin, was associated with increased anorexia and pain.

Conclusion

Metabolomics may advance our understanding of the biologic pathways contributing to uremic symptoms. Results from this hypothesis-generating study identify metabolites that may contribute to symptoms and warrant further investigation.

Funding

  • NIDDK Support