Indoxyl Sulfate Predicts Cardiovascular Disease and Renal Function Deterioration in Advanced Chronic Kidney Disease

Lin, Cheng‐Jui; Liu, Hsuan‐Liang; Pan, Chi-Feng; Chen, Chuang; Jayakumar, Thanasekaran; Wang, Tuen-Jen; Chen, Han‐Hsiang; Wu, Chih‐Jen

doi:10.1016/j.arcmed.2012.08.002

Cited by 123 publications

(95 citation statements)

References 25 publications

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“…In CKD patients, serum indoxyl sulphate levels have been shown to have an inverse relationship with kidney function and a direct relationship with aortic calcification, pulse-wave velocity, first heart failure event, and all-cause and cardiovascular mortality [75][76][77]. The mortality association remained after adjustment for age, gender, diabetes mellitus, albumin, hemoglobin, phosphorus levels, and aortic calcification [75].…”

Section: Cardiovascular Disease and Mortalitymentioning

confidence: 74%

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

et al. 2018

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In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects. In this review, we discuss the evidence supporting a role for gut-derived uremic toxins in promoting multiorgan dysfunction via inflammatory, oxidative stress, and apoptosis pathways. End-organ effects include vascular calcification, kidney fibrosis, anemia, impaired immune system, adipocyte dysfunction with insulin resistance, and low turnover bone disease. Higher blood levels of gut-derived uremic toxins are associated with increased cardiovascular events and mortality in the CKD population. Clinical trials that have examined interventions to trap toxic products or reverse gut microbial dysbiosis via oral activated charcoal AST-120, prebiotics and probiotics have not shown impact on cardiovascular or survival outcomes but were limited by sample size and short trials. In summary, the gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD.

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Section: Cardiovascular Disease and Mortalitymentioning

confidence: 74%

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

et al. 2018

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“…Lin et al (26) indicated that IS was a valuable marker in predicting cardiovascular events in patients with advanced CKD. In patients on hemodialysis, Taki et al (27) found that IS was significantly associated with the risk factors of atherosclerosis, pentosidine, and HDL-cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

Cao

Chen

Zou

et al. 2015

Clinical Journal of the American Society of Nephrology

100

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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. ResultsIn total, 258 patients (145 men) with a mean age of 57.0614.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate #32.35 mg/ml) and the high-indoxyl sulfate group (indoxyl sulfate .32.35 mg/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.

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“…Recent studies have shown that serum indoxyl sulfate levels are a reliable marker in predicting CVD, and that indoxyl sulfate and p-cresyl sulfate are reliable CKD progression markers in CKD patients [61,67,68].…”

Section: • Intestinal Microbiota and Inflammation And Cvd In Ckd Patientsmentioning

confidence: 99%

Role of Altered Intestinal Microbiota in Systemic Inflammation and Cardiovascular Disease in Chronic Kidney Disease

et al. 2014

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The normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, the alteration of the intestinal microbiota has been shown to contribute to the pathogenesis of several pathological conditions, including obesity and insulin resistance, among others. Recent studies have revealed profound alterations of the gut microbial flora in patients and animals with chronic kidney disease (CKD). Alterations in the composition of the microbiome in CKD may contribute to the systemic inflammation and accumulation of gut-derived uremic toxins, which play a central role in the pathogenesis of accelerated cardiovascular disease and numerous other CKD-associated complications. This review is intended to provide a concise description of the potential role of the CKD-associated changes in the gut microbiome and its potential role the pathogenesis of inflammation and uremic toxicity. In addition, the potential efficacy of pre- and pro-biotics in the restoration of the microbiome is briefly described.

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Indoxyl Sulfate Predicts Cardiovascular Disease and Renal Function Deterioration in Advanced Chronic Kidney Disease

Cited by 123 publications

References 25 publications

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

Role of Altered Intestinal Microbiota in Systemic Inflammation and Cardiovascular Disease in Chronic Kidney Disease

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