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Metabolites linked to a range of symptoms experienced by people with chronic kidney disease

Researchers have identified metabolites (molecular byproducts of metabolism) that are associated with specific symptoms of uremia—a condition in which poor blood filtration from reduced kidney function leads to a buildup of toxins in the blood—a discovery that could one day lead to improved care for people with chronic kidney disease (CKD). People with CKD often experience a range of uremic symptoms that adversely affect quality of life. These symptoms can be gastrointestinal (e.g., loss of appetite, nausea, vomiting) or neurologic (e.g., reduced alertness, forgetfulness, lack of energy) in nature. While blood toxins are known to contribute to uremic symptoms, the specific causative metabolites are unknown. In a recent study, scientists determined the blood levels of more than 1,100 metabolites in 695 participants with CKD (38 percent female; 86 percent White) and developed a “score” for each uremic symptom based on reported severity and duration in each individual. They then looked for associations between metabolite levels and symptom scores. Eleven metabolites were found to be associated with gastrointestinal symptoms and seven metabolites were associated with neurological symptoms. The authors acknowledge that the size of the cohort was relatively small, and the relative representation of CKD causes within the cohort may limit the applicability of the findings. Laboratory testing, validation, and randomized controlled trials would be needed to determine definitively whether specific metabolites cause certain uremic symptoms. Further studies of the metabolites identified in this study could lead to novel therapeutic approaches to alleviate the uremic symptoms experienced by many people with CKD.

Hu J-R, Myint L, Levey AS,…Shafi T. A metabolomics approach identified toxins associated with uremic symptoms in advanced chronic kidney disease. Kidney Int 101: 369-378, 2022.

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