Suppressive Effect of an Oral Sorbent on the Accumulation of &lt;i&gt;p&lt;/i&gt;-Cresol in the Serum of Experimental Uremic Rats

Niwa, Toshimitsu; Ise, Mikiko; Miyazaki, Takashi; Meada, Kenji

doi:10.1159/000187446

Cited by 62 publications

(30 citation statements)

References 12 publications

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“…An oral adsorbent, AST-120 (Kremezin), is effective in removing uremic toxins or their precursors such as indole, indoxyl sulfate [4, 5, 6]and p -cresol [7]from the gastrointestinal tract and retards the progression of renal failure and renal fibrosis in experimental rats with kidney disease [5, 8, 9, 10, 11, 12]. Furthermore, clinical studies showed that AST-120 could also delay the progression of CRF and the initiation of dialysis therapy in undialyzed uremic patients [6].…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy with Benazepril and Oral Adsorbent Ameliorates Progressive Renal Fibrosis in Uremic Rats

Aoyama

Shimokata

Niwa³

2002

Nephron

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Background/Aims: The administration of an angiotensin-converting enzyme (ACE) inhibitor or an oral adsorbent, AST-120 (Kremezin), prevents the progression of renal failure. This study was designed to determine the additional effects of AST-120 combined with an ACE inhibitor, benazepril, on the progression of renal fibrosis in uremic rats. Methods: 5/6-nephrectomized uremic rats were divided into control uremic rats (CRF group), benazepril-treated uremic rats (CRF+B group) and uremic rats receiving benazepril and AST-120 (CRF+BK group). After 14 weeks of treatment renal function and pathological changes were investigated. Results: The progression of renal dysfunction was delayed in both the CRF+B and CRF+BK groups as compared with the CRF group. In the CRF+BK group, the level of serum and urinary indoxyl sulfate and the tubular accumulation of indoxyl sulfate decreased. Both the CRF+B and CRF+BK groups showed lower glomerular sclerosis indices than the CRF group. In the CRF+BK group, but not the CRF+B group, the interstitial fibrosis area and the expression of transforming growth factor (TGF) β1 and tissue inhibitor of metalloproteinases (TIMP) 1 were decreased as compared with the CRF group. Furthermore, the CRF+BK group showed a smaller interstitial fibrosis area and a lower renal osteopontin expression than the CRF+B group. Conclusion: Combination therapy of benazepril and AST-120 is more effective than benazepril alone in retarding the progression of interstitial fibrosis by reducing the expression of TGF-β1, TIMP-1 and osteopontin.

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Section: Introductionmentioning

confidence: 99%

Combination Therapy with Benazepril and Oral Adsorbent Ameliorates Progressive Renal Fibrosis in Uremic Rats

Aoyama

Shimokata

Niwa³

2002

Nephron

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“…AST-120 (Kremezin®) is an intestinal sorbent with the capacity to decrease plasma concentration of indoxyl sulfate [58] and maybe other protein-bound uremic solutes such as the cresols as well [59]; AST-120 was shown in animal experiments to prevent progression of kidney injury and glomerulosclerosis [60,61] and in a number of interventional trials, it improved clinical outcome parameters [62,63]. …”

Section: Interventional Outcome Studies Based On Removalmentioning

confidence: 99%

Advantages of New Hemodialysis Membranes and Equipment

Vanholder

Glorieux

Biesen³

2009

Nephron Clin Pract

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Chronic kidney disease is characterized by the progressive retention of a number of compounds, several of which have the potential to cause cardiovascular damage. Many of these are difficult to remove by standard dialysis strategies. Removal of the larger middle molecules (mostly larger peptidic compounds) can be obtained by increasing dialyzer pore size and/or by applying convective strategies. For protein-bound solutes, convection (essentially hemodiafiltration) positively affects removal. The HEMO study demonstrated outcome superiority for the large-pore high-flux hemodialysis membranes in a number of subgroup analyses. Likewise, the Membrane Permeability Outcome study showed outcome superiority for high flux in patients with serum albumin <4 g/dl, the group for which the study had originally been designed. Apart from a small controlled trial, data suggesting superiority for convective strategies are all observational.

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“…AST-120 consists of fine spherical particles, approximately 0.2–0.4 mm in diameter, composed of porous microcrystalline carbon with an oxygen complex including a surface oxide. AST-120 can adsorb low-molecular-weight substances such as creatinine, urea, guanidine compounds, indole, polyamines, hippuric acid, p -cresol and vasoactive intestinal contractor in the gastrointestinal tract, and it is excreted into the feces along with these substances [16,17,18]. Because indole is a precursor of indoxyl sulphate, AST-120 can reduce the serum level of indoxyl sulphate, which is a uremic toxin that accelerates the progression of CRF [19].…”

Section: Introductionmentioning

confidence: 99%

Oral Adsorbent Prevents Reduction of Anionic Sites of the Glomerular Basement Membrane in Diabetic Nephropathy

Okada

Matsumoto²,

Takahashi³

2004

Nephron Exp Nephrol

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Background: AST-120, an oral adsorbent, inhibits progression of diabetic nephropathy by reducing albuminuria. The purpose of the present study was to explore the mechanism underlying the protective effect of AST-120 against albuminuria. Methods: Twenty-four male Sprague-Dawley rats underwent intravenous injection of streptozotocin and subsequent uninephrectomy. Half of the rats were fed standard rat chow, and the other half were fed rat chow containing AST-120. All rats were killed at week 6 after a clearance study. Results: There were no significant differences in body weight, kidney weight, urinary volume, blood pressure, blood glucose or inulin clearance between the two groups at week 6. However, urinary albumin excretion at week 6 was significantly lower in the AST-120 group than in the control group (p < 0.05). Light microscopic observation showed that the planar area of glomeruli was significantly smaller in the AST-120 group than in the control group (p < 0.01), and the shortest diameter of proximal tubules was less in the AST-120 group than in the control group (p < 0.01). Electron microscopic observation showed a significantly greater number of anionic sites on the lamina rara externa of the glomerular basement membrane in the AST-120 group than in the control group (p < 0.01). Conclusion: We conclude that AST-120 reduces albuminuria by preventing the decrease in the number of anionic sites in the glomerular basement membrane in rats with diabetic nephropathy. In addition, AST-120 inhibits the appearance of glomerular and tubular hypertrophy.

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Suppressive Effect of an Oral Sorbent on the Accumulation of <i>p</i>-Cresol in the Serum of Experimental Uremic Rats

Cited by 62 publications

References 12 publications

Combination Therapy with Benazepril and Oral Adsorbent Ameliorates Progressive Renal Fibrosis in Uremic Rats

Combination Therapy with Benazepril and Oral Adsorbent Ameliorates Progressive Renal Fibrosis in Uremic Rats

Advantages of New Hemodialysis Membranes and Equipment

Oral Adsorbent Prevents Reduction of Anionic Sites of the Glomerular Basement Membrane in Diabetic Nephropathy

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