Therapeutic Effects of Oral Sorbent in Undialyzed Uremia

Sanaka, Tsutomu; Sugino, Nobuhiro; Teraoka, Satoshi; Ota, Kazuo

doi:10.1016/s0272-6386(88)80002-7

Cited by 73 publications

(68 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This drug has been shown to retard the deterioration of renal function in these patients through reducing the systemic levels of uremic toxins by adsorbing them in the gastrointestinal tract. [1,2] Indoxyl sulfate is known to be one of the uremic toxins that are harmful to the kidney and contribute to the progression of CKD. [3,4] AST-120 decreases the levels of indoxyl sulfate in serum and urine of CKD patients by adsorbing indole, the precursor of indoxyl sulfate, in the intestine, thereby reducing the burden of indoxyl sulfate on the nephrons and retarding the progression of renal insufficiency.…”

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

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: 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

“…The oral carbonaceous adsorbent, AST-120 (Kremezin \ ), has been used in pre-dialysis, uremic stage renal failure patients to adsorb biologically active substances, the so-called uremic toxins, in the circulation that accumulate during CRF, thereby prolonging the progression of CRF and the interval to the inception of dialysis (4)(5)(6)(7). In nephrectomy animal models, the administration of AST-120 attenuates the progression of renal failure without affecting the plasma rennin-angiotensin system or protein intake and reduces the gene expression of transforming growth factor-b 1 (TGF-b 1 ), a tissue inhibitor of metalloproteinease (TIMP-1) and pro-a1(I) collagen in the kidney (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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

Anraku²,

Kitamura³

et al. 2007

Pharm Res

103

View full text Add to dashboard Cite

Purpose. The effect of AST-120, an oral adsorbent, on oxidative stress in the systemic circulation in chronic renal failure (CRF) was examined and the potential role of indoxyl sulfate (IS), an uremic toxin adsorbed by AST-120, in inducing the formation of reactive oxygen species (ROS) in the vascular system was studied, in vitro and in vivo. Materials and methods. The level of oxidized albumin, a marker for oxidative stress in the systemic circulation was determined by HPLC, as previously reported. The mRNA levels of TGF-b 1 and Oat1 were measured by quantitative RT-PCR. The IS induced ROS generation in cultured human umbilical vein endothelial cells (HUVECs) was estimated using a fluorescence microplate reader.Results. An increase in the ratio of oxidized to unoxidized albumin was determined using 5/6 nephrectomized rats (CRF rats) compared to a control group. The ratio was significantly reduced in the group that received AST-120 of 4 weeks, suggesting that AST-120 inhibits oxidative stress in CRF. An anti-oxidative effect of AST-120 was also observed in CRF rats with a similar renal function. The ratio of oxidized albumin was correlated with serum IS levels in vivo. The same relationship was also observed in CRF rats with the continued administration of IS. In addition, IS dramatically increased the generation of ROS in both a dose-and time-dependent manner in HUVEC, suggesting that accumulated IS may play an important role in enhancing intravascular oxidative stress. Conclusion. We propose that AST-120 reduces IS concentrations in the blood that induces ROS production in endothelial cells, thereby inhibiting the subsequent occurrence of oxidative stress in the systemic circulation in renal failure.

show abstract

“…Carbonaceous molecules such as activated charcoal are an adsorbent of gaseous and non-gaseous molecules (2). AST-120 (Cremedin®), which consists of spherical porous car bonaceous particles with a diameter of 0.2 to 0.4 mm, has been used clinically as an enteral adsorbent of uremic toxins in progressive renal disease (3,4). We hypothesized that such a non-specific adsorbent may quench NO be cause AST-120 is an analog of activated charcoals that are widely used as an adsorbent of NOX in industry.…”

mentioning

confidence: 99%

“…AST-120 has been used as an adsorbent of uremic toxins (3). It has been shown to adsorb uremic molecules by an enteral exchange of molecules through the epitheli um.…”

mentioning

confidence: 99%

Quenching of Nitric Oxide by an Oral Carbonaceous Adsorbent.

Iwamoto¹,

Ito²,

Kakuchi

et al. 1997

Jpn.J.Pharmacol

View full text Add to dashboard Cite

ABSTRACT-The ability of carbonaceous particles (AST-120), originally developed as an enteral adsorbent of uremic toxins, to quench nitric oxide (NO) was tested. NO in solutions prepared by two methods [NO gas bubbling and NO generating system, i.e., decomposition of 1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl 1-triazene] were determined by a NO-specific reduction of carboxy-2-phenyl-4,4,5,5-tetramethyl-imidaz oline-l-oxyl-3-oxide using an electron paramagnetic resonance spectrometry. NO concentrations were less in samples containing increasing concentrations of AST-120. In a separate study, nitrite concentrations in lipopolysaccharide-treated RAW264 cells were significantly less in incubation medium containing AST-120. Thus, AST-120 may be applicable as an enteral anti-NO agent.

show abstract

Therapeutic Effects of Oral Sorbent in Undialyzed Uremia

Cited by 73 publications

References 8 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

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

Quenching of Nitric Oxide by an Oral Carbonaceous Adsorbent.

Contact Info

Product

Resources

About