Association Between Indoxyl Sulfate and Cardiac Dysfunction and Prognosis in Patients With Dilated Cardiomyopathy

Shimazu, Shuzo; Hirashiki, Akihiro; Okumura, Takahiro; Yamada, Takashi; Okamoto, Rie; Shinoda, Norihiro; Takeshita, Kyosuke; Kondo, Takahisa; Niwa, Toshimitsu; Murohara, Toyoaki

doi:10.1253/circj.cj-12-0715

Cited by 56 publications

(41 citation statements)

References 40 publications

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“…Shimazu et al (34) reported that serum IS was associated with cardiac dysfunction and predicted cardiac events (cardiac death or hospitalization for worsening of heart failure) in 76 patients with dilated cardiomyopathy and normal kidney function or mild to moderate CKD. However, the result was negative after adjustment for other risk factors.…”

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

102

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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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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

102

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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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“…This result is in agreement with previous reports. 32, 33 The prognostic value of blood IS in this patient type, however, has not been fully elucidated. We found that blood IS level is a useful prognostic marker in patients with eGFR 59-30 ml · min -1 · 1.73 m -2 .…”

Section: Discussionmentioning

confidence: 99%

Plasma Indoxyl Sulfate and Estimated Glomerular Filtration Rate

Yoshikawa

Ishii

Suzuki

et al. 2014

Circ J

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Background: Indoxyl sulfate (IS), a uremic toxin, has cardiovascular as well as uremic toxicity. We evaluated the prognostic value of blood IS level for long-term outcome. Methods and Results:This study followed 311 patients with coronary artery disease. Plasma IS level and estimated glomerular filtration rate (eGFR) were determined. The endpoint was a major adverse cardiac event (MACE). Median follow-up was 759 days. IS was significantly higher in patients with MACE than in those without (P<0.001). Patients were divided according to quartiles (Q) of plasma IS level (Q1, Q2, Q3, and Q4). On Kaplan-Meier analysis a significantly lower MACE-free rate was obtained for Q4 compared with the other quartiles (P<0.001). In patients with eGFR ≥90, 89-60, 59-30, 29-15, and <15 ml · min -1 · 1.73 m -2 , the percentage of patients in Q4 was 0%, 13%, 29%, 100%, and 100%, respectively. In patients with eGFR 89-60 ml · min -1 · 1.73 m -2 , there was no significant difference in MACE-free rate between Q4 and the other quartiles; in patients with eGFR 59-30 ml · min -1 · 1.73 m -2 , a significantly lower MACE-free rate was obtained for Q4 compared with the other quartiles (P=0.832 and P=0.015, respectively). Conclusions:Plasma IS level is a significant predictor of MACE, especially in patients with eGFR 59-30 ml · min -1 · 1.73 m -2 . (Circ J 2014; 78: 2477 -2482

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Association Between Indoxyl Sulfate and Cardiac Dysfunction and Prognosis in Patients With Dilated Cardiomyopathy

Cited by 56 publications

References 40 publications

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

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

Plasma Indoxyl Sulfate and Estimated Glomerular Filtration Rate

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