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

Wenji Wang, Guihua Hao, Yu Pan, Shuai Ma, Tianye Yang, Peng Shi, Qiuyu Zhu, Yingxin Xie, Shaojun Ma, Qi Zhang, Hong Ruan, Feng Ding, Wenji Wang, Guihua Hao, Yu Pan, Shuai Ma, Tianye Yang, Peng Shi, Qiuyu Zhu, Yingxin Xie, Shaojun Ma, Qi Zhang, Hong Ruan, Feng Ding

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00953992.

Keywords: Acute kidney injury; Indoxyl sulfate; Prognosis; Protein-bound solute.

Conflict of interest statement

Ethics approval and consent to participate

Approval was obtained from the ethics committee of Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University (approval number: [2014]45). Written informed consent was obtained from either the patients or their legal guardians prior to their participating in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of study progress. HIS, hospital information system; Scr, serum creatinine; RPGN, rapidly progressing glomerulonephritis
Fig. 2
Fig. 2
Kaplan-Meier proportion of surviving patients after 90 days of observation according to the 2 a priori-selected groups of uremic toxins in 262 patients occurring AKI. (a) IS, unadjusted; (b) IS, adjusted for age, gender, non-renal APACHE II score, sepsis, RRT, surgery, serum albumin, creatinine, BUN, β2-microglobulin, ALT, neutrophilic granulocyte and platelet counts; (c) β2-microglobulin, unadjusted; (d) β2-microglobulin, adjusted for age, gender, non-renal APACHE II score, sepsis, RRT, surgery, serum albumin, IS, creatinine, BUN, ALT, neutrophilic granulocyte and platelet counts; (e) Creatinine, unadjusted; (f) Creatinine, adjusted for age, gender, non-renal APACHE II score, sepsis, RRT, surgery, serum albumin, IS, BUN, β2-microglobulin, ALT, neutrophilic granulocyte and platelet counts. The cutoff point for serum IS is 2.74 μg/ml, while that for serum creatinine is 167 μmol/L, and that for β2-microglobulin is 5.07 mg/L
Fig. 3
Fig. 3
The changes of concentrations of uremic toxins in 89 patients occurring AKI. (a) serum indoxyl sulfate (IS); (b) serum β2-microglobulin (beta2-MG); (c) serum creatinine (Scr)

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