Inverted U-Curve Association between Serum Indoxyl Sulfate Levels and Cardiovascular Events in Patients on Chronic Hemodialysis

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.