Serum total indoxyl sulfate and clinical outcomes in hemodialysis patients: results from the Japan Dialysis Outcomes and Practice Patterns Study

BACKGROUND: Uremic toxins are associated with various chronic kidney disease-related comorbidities. Indoxyl sulfate (IS), a protein-bound uremic toxin, reacts with vasculature, accelerating atherosclerosis and/or vascular calcification in animal models. Few studies have examined the relationship of IS with clinical outcomes in a large cohort of hemodialysis (HD) patients. METHODS: We included 1170 HD patients from the Japan Dialysis Outcomes and Practice Patterns Study Phase 5 (2012–15). We evaluated the associations of serum total IS (tIS) levels with all-cause mortality and clinical outcomes including cardiovascular (CV)-, infectious- and malignancy-caused events using Cox regressions. RESULTS: The median (interquartile range) serum tIS level at baseline was 31.6 μg/mL (22.6–42.0). Serum tIS level was positively associated with dialysis vintage. Median follow-up was 2.8 years (range: 0.01–2.9). We observed 174 deaths (14.9%; crude rate, 0.06/year). Serum tIS level was positively associated with all-cause mortality [adjusted hazard ratio per 10 μg/mL higher, 1.16; 95% confidence interval (CI) 1.04–1.28]. Association with cause-specific death or hospitalization events, per 10 μg/mL higher serum tIS level, was 1.18 (95% CI 1.04–1.34) for infectious events, 1.08 (95% CI 0.97–1.20) for CV events and 1.02 (95% CI 0.87–1.21) for malignancy events after adjusting for covariates including several nutritional markers. CONCLUSIONS: In a large cohort study of HD patients, serum tIS level was positively associated with all-cause mortality and infectious events.