Xue-Sen Cao1, Jun Chen2, Jian-Zhou Zou1, Yi-Hong Zhong1, Jie Teng1, Jun Ji1, Zhang-Wei Chen3, Zhong-Hua Liu1, Bo Shen1, Yu-Xin Nie1, Wen-Lv Lv1, Fang-Fang Xiang1, Xiao Tan1, Xiao-Qiang Ding4. 1. Department of Nephrology, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital; 2. Department of Pharmaceutics, School of Pharmacy; and. 3. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. 4. 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.
Abstract
BACKGROUND AND OBJECTIVES: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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.
BACKGROUND AND OBJECTIVES: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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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: Timothy W Meyer; Jason L Walther; Maria Enrica Pagtalunan; Andres W Martinez; Ali Torkamani; Patrick D Fong; Natalie S Recht; Channing R Robertson; Thomas H Hostetter Journal: Kidney Int Date: 2005-08 Impact factor: 10.612
Authors: C Zoccali; S Bode-Böger; F Mallamaci; F Benedetto; G Tripepi; L Malatino; A Cataliotti; I Bellanuova; I Fermo; J Frölich; R Böger Journal: Lancet Date: 2001 Dec 22-29 Impact factor: 79.321
Authors: T Nii-Kono; Y Iwasaki; M Uchida; A Fujieda; A Hosokawa; M Motojima; H Yamato; K Kurokawa; M Fukagawa Journal: Kidney Int Date: 2007-01-31 Impact factor: 10.612
Authors: H Yamamoto; S Tsuruoka; T Ioka; H Ando; C Ito; T Akimoto; A Fujimura; Y Asano; E Kusano Journal: Kidney Int Date: 2006-05 Impact factor: 10.612
Authors: Matthew B Rivara; Leila R Zelnick; Andrew N Hoofnagle; Rick Newitt; Russell P Tracy; Mario Kratz; David S Weigle; Bryan R Kestenbaum Journal: Clin Chem Date: 2017-02-10 Impact factor: 8.327
Authors: Anne M Koning; Wouter C Meijers; Isidor Minović; Adrian Post; Martin Feelisch; Andreas Pasch; Henri G D Leuvenink; Rudolf A de Boer; Stephan J L Bakker; Harry van Goor Journal: Am J Physiol Heart Circ Physiol Date: 2016-12-06 Impact factor: 4.733
Authors: Feby Savira; Ruth Magaye; Danny Liew; Christopher Reid; Darren J Kelly; Andrew R Kompa; S Jeson Sangaralingham; John C Burnett; David Kaye; Bing H Wang Journal: Br J Pharmacol Date: 2020-05-13 Impact factor: 8.739