Abstract
Background: Protein-bound uremic toxins are associated with cardiovascular disease and mortality in patients with chronic kidney disease. We investigated their association with clinical outcomes in patients undergoing chronic hemodialysis (CHD). Methods: A prospective cohort study was conducted on 86 Taiwanese patients undergoing CHD. The predictors were indoxyl sulfate and p-cresyl sulfate concentrations, with each analyzed as three tertiles. Outcomes were cardiovascular events and all-cause mortality. Results: During a 25-month follow up period, there were 23 cardiovascular events and seven all-cause mortality events. In the crude survival analysis, the second indoxyl sulfate tertile was shown to be a powerful predictor of cardiovascular events compared with the third tertile (hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.10–8.94), and the first tertile was shown to have a poor but insignificant cardiovascular outcome (HR, 1.09; 95% CI, 0.30–4.00). Moreover, the predictive power of the second indoxyl sulfate tertile for cardiovascular events remained after adjustment for confounders (HR, 5.42; 95% CI, 1.67–17.60). Conclusions: An inverse U-curve relationship was observed between the total serum indoxyl sulfate level and cardiovascular events in our CHD patients. A large-scale study is needed to confirm this relationship.
Highlights
Cardiovascular disease (CVD) is significantly more prevalent in patients on chronic hemodialysis (CHD) than in the general population because of the increased oxidative stress and inflammation, which contribute to vascular abnormalities that are associated with a higher death rate
Eighty-six stable hemodialysis patients were enrolled in this prospective study
A comparison of patients divided by indoxyl sulfate (IS) tertiles revealed no significant intergroup differences with respect to age, gender, body mass index (BMI), diabetes mellitus status, systolic and diastolic arterial pressure values, lipid profile, calcium phosphate product, CRP, hemoglobin content, dialysis adequacy, HD vintage, or a positive history for cardiovascular events
Summary
Cardiovascular disease (CVD) is significantly more prevalent in patients on chronic hemodialysis (CHD) than in the general population because of the increased oxidative stress and inflammation, which contribute to vascular abnormalities that are associated with a higher death rate. Protein-bound uremic toxins (PBUTs) have been implicated in uremic syndrome and may play an important role in the mortality and morbidity rates of patients with chronic kidney disease (CKD) [4,5]. P-Cresol, an end-product of tyrosine metabolism in the gastrointestinal tract, exists predominantly as conjugated PCS in vivo; unconjugated p-cresol is not detectable [13] It decreases the activation in a concentration-dependent and skeletal resistanceof to polymorphonuclear parathyroid hormonegranulocytes (PTH) in dialysis patients [11,12]. An increased level as conjugated PCS in vivo; unconjugated p-cresol is not detectable [13] It decreases of serum-free p-cresol was found to be related to higher mortality and morbidity rates the activation of polymorphonuclear granulocytes in a concentration-dependent manner,. CV events and death) in CHD patients during a 25-month follow-up period
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