Serum total indoxyl sulfate and clinical outcomes in hemodialysis patients: results from the Japan Dialysis Outcomes and Practice Patterns Study
Suguru Yamamoto, Douglas S. Fuller, Hirotaka Komaba, Takanobu Nomura, Ziad A. Massy, Brian Bieber, Bruce Robinson, Ronald L. Pisoni, Masafumi Fukagawa
Abstract
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.