Serum indoxyl sulfate is associated with mortality in hospital-acquired acute kidney injury: a prospective cohort study

BACKGROUND: Protein-bound uremic toxins are associated with poor outcomes in patients with chronic kidney disease. The aim of this study is to investigate the relationship between indoxyl sulfate (IS), a protein-bound solute, and 90-day mortality in patients with acute kidney injury. METHODS: Adults with hospital-acquired AKI (HA-AKI) were enrolled in this prospective cohort study between 2014 and 2015, according to the KDIGO creatinine criteria. The primary end point was all-cause death during follow-up. RESULTS: The mean serum IS level in patients with HA-AKI was 2.74 ± 0.75 μg/ml, which was higher than that in healthy subjects (1.73 ± 0.11 μg/ml, P < 0.001) and critically ill patients (2.46 ± 0.35 μg/ml, P = 0.016) but was lower than that in patients with chronic kidney disease (3.07 ± 0.31 μg/ml, P < 0.001). Furthermore, serum IS levels (2.83 ± 0.55 μg/ml) remained elevated in patients with HA-AKI on the seventh day after AKI diagnosis. Patients with HA-AKI were divided into the following two groups according to the median serum IS level: the low-IS group and the high-IS group. A total of 94 (35.9%) patient deaths occurred within 90 days, including 76 (29.0%) in the low-IS group and 112 (42.7%) in the high-IS group (P = 0.019). Kaplan-Meier analysis revealed that the two groups differed significantly with respect to 90-day survival (log-rank P = 0.007), and Cox regression analysis showed that an IS level ≥ 2.74 μg/ml was significantly associated with a 2.0-fold increased risk of death (adjusted hazard ratio [HR], 2.92; 95% confidence interval [CI], 1.76 to 4.86; P < 0.001) compared with an IS level < 2.74 μg/ml. CONCLUSIONS: Serum IS levels were significantly elevated in patients with HA-AKI compared to those in healthy subjects and critically ill patients and were associated with a worse prognosis of HA-AKI. TRIAL REGISTRATION: www.clinicaltrials.gov NCT 00953992. Registered 6 August 2009.