An Oral Adsorbent, AST-120 Protects Against the Progression of Oxidative Stress by Reducing the Accumulation of Indoxyl Sulfate in the Systemic Circulation in Renal Failure

Shimoishi, Kazuki; Anraku, Makoto; Kitamura, Kenichiro; Tasaki, Yuka; Taguchi, Kazuaki; Hashimoto, Mitsuru; Fukunaga, Eiko; Maruyama, Toru; Otagiri, Masaki

doi:10.1007/s11095-007-9248-x

Cited by 103 publications

(100 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, other groups reported that indoxyl sulfate promoted oxidative stress in endothelial cells and the kidney. [16][17][18][19] These results strongly suggest the involvement of uremic toxins in the development of atherosclerosis. AST-120 has been known to decrease serum levels of indoxyl sulfate significantly in CKD rat models and also in CKD patients.…”

Section: Discussionmentioning

confidence: 70%

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

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.

show abstract

Section: Discussionmentioning

confidence: 70%

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

“…26,27 Therefore, IS accumulation may enhance O 2 À production and oxidative/nitrative stress in vascular endothelial cells, followed by endothelial dysfunction. We investigated the mRNA expression of p47phox, one of the NADPH oxidase components, in the aorta to elucidate the pathogenic mechanism of O 2 À production by IS.…”

Section: Discussionmentioning

confidence: 99%

“…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%

See 1 more Smart Citation

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

“…AST-120 is a carbonaceous adsorbent that is used to treat CKD patients in Japan. It has been reported that AST-120 removes uremic toxins and reduces oxidative stress [13,14]. The duration of nephrologist care was defined as the length of followup days by nephrologists prior to the initiation of HD.…”

Section: Data Collectionmentioning

confidence: 99%

Effect of long-acting erythropoiesis-stimulating agents on hemoglobin levels at the initiation of dialysis

et al. 2016

View full text Add to dashboard Cite

Background: The goal of the present study was to explore the differences in effects between erythropoiesisstimulating agent (ESA) types on hemoglobin (Hb) level at the initiation of maintenance dialysis. Methods: This was a cross-sectional study. From January 2006 to October 2012, 2920 patients with end-stage kidney disease commenced hemodialysis (HD) at nine participating hospitals. The criteria for exclusion from the database were (1) presence of cancer or gastrointestinal bleeding and (2) serum C-reactive protein ≥0.3 mg/dL. A total of 1263 patients were entered into the final database. We explored the association of yearly trend of Hb level just before the first HD session with the different types of ESA in the predialysis period. Results: During the 7-year study period, patients' Hb levels at the initiation of dialysis dramatically increased from 8.6 to 9.1 g/dL. Parallel to this increase, the use of long-acting ESA also increased from 0 to 80 %. A higher level of Hb was confirmed in the long-acting ESA group compared with the short-acting group (9.5 vs. 8.7 g/dL, P < 0.01). Multivariate regression analysis showed a strong association of Hb level with the use of long-acting ESA (r = 0.155, P = 0.003), even after adjusting for confounding variables and estimated dose of epoetin.

show abstract

An Oral Adsorbent, AST-120 Protects Against the Progression of Oxidative Stress by Reducing the Accumulation of Indoxyl Sulfate in the Systemic Circulation in Renal Failure

Cited by 103 publications

References 29 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 long-acting erythropoiesis-stimulating agents on hemoglobin levels at the initiation of dialysis

Contact Info

Product

Resources

About