title: Association of indoxyl sulfate with heart failure among patients on hemodialysis.
abstract: OBJECTIVE
  Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis.
  
  
  METHODS
  Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up.
  
  
  RESULTS
  In total, 258 patients (145 men) with a mean age of 57.0 ± 14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤ 2.35 μg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 μg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5-48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan-Meier analysis revealed the incidence of first heart failure event in the high-indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001).
  
  
  CONCLUSIONS
  Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Xue-Sen
authors.initials: XS
authors.lastname: Cao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy; and.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Jian-Zhou
authors.initials: JZ
authors.lastname: Zou
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Zhong
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Jie
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhang-Wei
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Nie
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Wen-Lv
authors.initials: WL
authors.lastname: Lv
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Xiang
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital;
authors.forename: Xiao
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital; ding.xiaoqiang@zs-hospital.sh.cn.
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D015994:Incidence; D007200:Indican / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007200:Indican
keywords: heart failure; hemodialysis; indoxyl sulfate; uremic toxin