The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair

Dou, Laetitia; Bertrand, Emanuel; Cérini, Claire; Faure, Valérie; Sampol, José; Vanholder, Raymond; Berland, Yvon; Brunet, Philippe

doi:10.1111/j.1523-1755.2004.00399.x

Cited by 429 publications

(344 citation statements)

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“…[4] Recent studies have suggested that indoxyl sulfate may also be involved in the mechanisms underlying the progression of atherosclerotic lesions in CKD patients. Dou et al [6] found that two uremic toxins, indoxyl sulfate and p-cresol, inhibited endothelial proliferation and decreased endothelial wound repair, and concluded that indoxyl sulfate and p-cresol may play a role in endothelial dysfunction in uremic patients. Bammens et al [14] reported that free serum concentrations of the protein-bound retention solute pcresol predict mortality in hemodialysis patients.…”

Section: Discussionmentioning

confidence: 99%

“…[5] Recent studies have suggested that increased serum levels of indoxyl sulfate and p-cresol in CKD patients may contribute to not only kidney damage but also to vascular lesions, including atherosclerotic lesions, which are closely related to cardiovascular events frequently observed in dialysis patients. [6,7] Cardiovascular diseases are the leading cause of mortality in CKD patients. [8] The above observations raise a possibility that reduction of circulating uremic toxins by AST-120 prior to the initiation of dialysis in CKD patients may improve their prognosis even after the initiation of dialysis.…”

Section: Introductionmentioning

confidence: 99%

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AST-120 Treatment in Pre-Dialysis Period Affects the Prognosis in Patients on Hemodialysis

Ueda¹,

Shibahara²,

Takagi

et al. 2008

Renal Failure

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Background/Aims. An oral adsorbent, AST-120, has been shown to retard the deterioration of renal function in patients with chronic kidney disease (CKD) by decreasing serum nephrotoxic substances such as indoxyl sulfate. Recent studies have suggested that a high level of serum indoxyl sulfate may be one of the mechanisms underlying the progression of atherosclerotic lesion, which is the leading cause of cardiovascular event or death in dialysis patients. In this study, we examined retrospectively whether AST-120 given to patients in the pre-dialysis period influences the prognosis after the initiation of dialysis. Methods. One hundred and ninety-two CKD patients on dialysis were studied. The survival and causes of death after the initiation of dialysis were compared between patients who were administrated AST-120 (AST-120 group, n = 101) and those not administrated AST-120 (non-AST-120 group, n = 91) prior to the initiation of dialysis. Results. The five-year survival rate was 72.6% in the AST-120 group and 52.6% in the non-AST-120 group, and was significantly higher in the AST-120 group (p = 0.018). The risk of death was increased 1.91-fold in the non-AST-120 group. However, no difference in the causes of death was observed between two groups. Conclusion. This study suggests that AST-120 given prior to the initiation of dialysis improves the prognosis of CKD patients under dialysis, although there is no association between AST-120 treatment and death caused by cardiovascular diseases such as heart failure, myocardial infarction, and cerebral hemorrhage. Further studies are needed to elucidate the effect of AST-120 on cardiovascular events and the prognosis in dialysis patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

AST-120 Treatment in Pre-Dialysis Period Affects the Prognosis in Patients on Hemodialysis

Ueda¹,

Shibahara²,

Takagi

et al. 2008

Renal Failure

View full text Add to dashboard Cite

show abstract

“…However, some in vitro studies have revealed the toxicity of IS in vascular cells. 14,33,34 In addition, oxidative stress induced by IS may damage vascular cells in an indirect manner. 26,27,36 Therefore, IS accumulation is considered to be one of the pathogenic mechanisms causing endothelial dysfunction in patients with CKD.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 IS inhibited endothelial proliferation and wound repair, and increased endothelial microparticles in human umbilical vein endothelial cells (HUVEC). In this study, we showed that the endothelium-dependent aortic response correlated significantly with serum IS levels.…”

Section: Discussionmentioning

confidence: 99%

Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy

et al. 2009

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It is important to consider a strategy to halt the development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Oral adsorbent AST-120 retards deterioration in renal function, reducing indoxyl sulfate (IS) accumulation. The aim of this study was to determine whether AST-120 improves endothelial dysfunction by reducing oxidative/nitrative stress in a rat-CKD model. Subtotally nephrectomized (Nx) rats aged 17 weeks were divided into two groups: control rats and rats orally treated with AST-120. Two weeks after initiation of AST-120, serum and urinary IS levels, renal histological scores and endothelium-dependent vascular responses (EDVRs) in the aorta were investigated. EDVR in 5-h incubation with 250 lg ml À1 IS was also examined in normal rat aortas. Nitrotyrosine content, mRNA expression of p47phox, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component, and expression and phosphorylation (serine-1177) of endothelial nitric oxide synthase (eNOS) in the aorta were examined in untreated and treated Nx rats. At the end of treatment, renal function and histological scores were not different in the two groups. AST-120 prevented the elevation of serum IS level in Nx rats, reducing urinary IS excretion, and ameliorated decreased EDVR in Nx rats. Incubation with IS tended to reduce EDVR in normal aortas, albeit insignificantly. AST-120 also suppressed nitrotyrosine accumulation and inhibited p47phox expression in Nx rats. The eNOS expression and phosphorylation were similar in the two groups. In conclusion, AST-120 ameliorated endothelial dysfunction and alleviated oxidative/nitrative stress in the aorta through reduced accumulation of IS, independent of renal function, in a rat CKD model.

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“…The reduced excretion of indoxyl sulfate in urine may indicate an elevated level in the serum of endothelial dysfunction rats. In an in vitro study, indoxyl sulfate induced endothelial dysfunction by inhibiting endothelial proliferation and migration [22]. It has been suggested that indoxyl sulfate also plays a role in oxidative stress by increasing NAD(P)H oxidase activity in endothelial cells and the production of reactive oxygen species (ROS), and by strongly decreasing the level of glutathione, one of the most active antioxidant systems in cells [23,24].…”

Section: Metabonomic Fingerprint Analysis Of Endothelial Dysfunctionmentioning

confidence: 99%

Effect of the traditional Chinese medicine tongxinluo on endothelial dysfunction rats studied by using urinary metabonomics based on liquid chromatography–mass spectrometry

Dai

Wang

Kong

et al. 2011

Journal of Pharmaceutical and Biomedical Analysis

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The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair

Abstract: We demonstrated that both p-cresol and indoxyl sulfate decrease endothelial proliferation and wound repair. These solutes could play a role in endothelial dysfunction observed in uremic patients.

Cited by 429 publications

References 44 publications

AST-120 Treatment in Pre-Dialysis Period Affects the Prognosis in Patients on Hemodialysis

AST-120 Treatment in Pre-Dialysis Period Affects the Prognosis in Patients on Hemodialysis

Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy

Effect of the traditional Chinese medicine tongxinluo on endothelial dysfunction rats studied by using urinary metabonomics based on liquid chromatography–mass spectrometry

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