Kidney Week

Abstract: SA-PO462

Metabolites Associated With Uremic Symptoms in Hemodialysis Patients

Session Information

• Hemodialysis and Frequent Dialysis: Clearance, Technology, Infection
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

• Myint, Leslie, Macalaster College, St. Paul, Minnesota, United States

Leslie Myint,

• Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States

Eugene P. Rhee,

• Wulczyn, Kendra E., Massachusetts General Hospital, Boston, Massachusetts, United States

Kendra E. Wulczyn,

• Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States

Sahir Kalim,

• Segev, Dorry L., NYU Langone Health, New York, New York, United States

Dorry L. Segev,

• McAdams-DeMarco, Mara, NYU Langone Health, New York, New York, United States

Mara McAdams-DeMarco,

• Thadhani, Ravi I., Massachusetts General Hospital, Boston, Massachusetts, United States

Ravi I. Thadhani,

• Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States

Sharon M. Moe,

• Moorthi, Ranjani N., Indiana University School of Medicine, Indianapolis, Indiana, United States

Ranjani N. Moorthi,

• Hostetter, Thomas H., University of North Carolina System, Chapel Hill, North Carolina, United States

Thomas H. Hostetter,

• Himmelfarb, Jonathan, University of Washington School of Medicine, Seattle, Washington, United States

Jonathan Himmelfarb,

• Meyer, Timothy W., Stanford University School of Medicine, Stanford, California, United States

Timothy W. Meyer,

• Powe, Neil R., University of California San Francisco, San Francisco, California, United States

Neil R. Powe,

• Tonelli, Marcello, University of Calgary, Calgary, Alberta, Canada

Marcello Tonelli,

• Shafi, Tariq, University of Mississippi Medical Center, Jackson, Mississippi, United States

Tariq Shafi,

Background

The specific substances causing uremic symptoms are unknown. We used untargeted metabolomics to identify metabolite markers associated with uremic symptoms in hemodialysis patients.

Methods

We profiled 29,591 plasma metabolites (Broad Institute) in 517 Longitudinal US/Canada Incident Dialysis (LUCID) study participants at baseline (discovery) and subset at year 1 (validation). We concurrently assessed uremic symptoms (KDQOL-36; fatigue, pruritus, anorexia, nausea/vomiting, daytime sleepiness, difficulty concentrating, and pain) and investigated demographic- and clinical covariate-adjusted associations using: a) metabolite-wise linear models with empirical Bayesian inference, accounting for multiple testing; b) LASSO; c) random forest (RF) models. We defined robust symptom-metabolite associations if significant in linear models and at least medium importance in both LASSO and RF models.

Results

The mean age was 61 years, 80% were male, and mean duration from dialysis initiation was 62 days. We identified several metabolites robustly associated with uremic symptoms; 3 metabolites associated with anorexia, 8 with pruritus, and 1 each with pain, sleepiness, and concentration (Table). Higher levels of 2-hydroxy-3-methylpentanoate/hydroxyisocaproate were linked to higher severity of anorexia, bodily pain, and difficulty concentrating. Lower levels of indoxyl sulfate were associated with higher severity of daytime sleepiness. No metabolites were significantly associated with fatigue or nausea/vomiting.

Conclusion

We identified several metabolites associated with uremic symptoms, which could be targeted for future interventions if replicated in other studies.

Funding

• Other NIH Support