中央研究院 Logo

Patients with chronic kidney disease (CKD) have a significantly higher incidence of cardiovascular (CV) events, attributable not only to the traditional CV risk factors, but also to the presence of a wide array of nontraditional risk factors that are unique to patients with CKD, such as anemia, volume overload, inflammation, oxidative stress, and uremic toxins. Indoxyl sulfate is one of the most studied gut-derived uremic toxins. We have previously shown that higher indoxyl sulfate levels were associated with a higher risk of incident peripheral artery disease but not coronary artery disease, stroke, or all-cause death in a cohort of hemodialysis patients. We have also shown that indoxyl sulfate was associated with immunosenescence in patients with CKD. Nevertheless, the determinants of individual indoxyl sulfate production remained unclear. We therefore developed an oral tryptophan challenge test to assess whether the indoxyl sulfate-producing capacity might differ from person to person and to identify factors associated with the interindividual variability. In the era of precision medicine, this approach may serve as a guidance for interventions to ameliorate the indoxyl sulfate toxicity for patients with CKD in the future. 

There are many conditions that may interfere with the composition of gut microbiota in patients with CKD, such as dietary patterns, medications, uremia-related complications, and comorbidities. The disturbance of normal gut microbiota, commonly called gut dysbiosis, may contribute to increased morbidity and mortality in this population. We have recently established the association of gut dysbiosis with two proinflammatory phenotypes, protein-energy wasting and normal weight obesity, and a higher risk of mortality in a cohort of patients with end-stage kidney disease requiring hemodialysis. The putative mechanisms underlying the link between gut dysbiosis and poor outcomes may include systemic inflammation and decreased short-chain fatty acid-producing bacteria. Further studies are also needed to determine whether gut microbe-derived metabolites beyond indoxyl sulfate play a prognostic role in patients with CKD.