An Oral Sorbent, AST-120, Increases Klotho Expression and Inhibits Cell Senescence in the Kidney of Uremic Rats

Adijiang, Ayinuer; Niwa, Toshimitsu

doi:10.1159/000264634

Cited by 40 publications

(33 citation statements)

References 32 publications

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“…In some studies with patients with CKD, AST-120 decreased serum and urinary IS levels and the levels of advanced glycation end products (AGEs) (24,25). Also, AST-120 increased the renal expression of Klotho, which was decreased in uremic condition and inhibited cell senescence in the kidney of uremic rats, probably by alleviating IS overload on the kidney (26).…”

Section: Discussionmentioning

confidence: 92%

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

Hui¹,

Kang²,

Park³

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives The notion that oral intestinal sorbent AST-120 slows renal disease progression has not been evaluated thoroughly. In this study, we investigated the long-term effect of AST-120 on renal disease progression (doubling of serum creatinine, eGFR decrease .50%, or initiation of RRT) in patients with advanced CKD.Design, setting, participants, & measurements We prospectively recruited 579 patients (CKD stage 3 or 4) from 11 medical centers in Korea from March 4, 2009 to August 31, 2010 and randomized them into an AST-120 arm and a control arm. Patients in the AST-120 arm were given 6 g AST-120 in three divided doses per day, and those in the control arm received only standard conventional treatment (open-label design) for 36 months or until the occurrence of primary outcomes.Results Levels of serum and urine indoxyl sulfate and b2-microglobulin decreased throughout the study period in both treatment arms; however, there was not a significant difference in change in uremic toxins in the AST-120 and control arms. The two arms were not different in the occurrence of composite primary outcomes (100 events in 272 individuals in the AST-120 arm and 100 events in 266 individuals in the control arm; hazard ratio, 1.12; 95% confidence interval, 0.85 to 1.48; log-rank P=0.45). The decline in eGFR and change in proteinuria were similar in the two treatment arms over time (P randomization-time =0.64 and P randomization-time =0.16, respectively). There was no difference in mortality (nine deaths in the AST-120 arm and 11 deaths in the control arm; log-rank P=0.73) or unplanned hospitalizations (102 in the AST-120 arm and 109 in the control arm; log-rank P=0.76) in the two treatment arms. There was no significant difference of the health-related quality of life score between the two arms.Conclusions Long-term use of AST-120 added to standard treatment did not change renal disease progression, proteinuria, mortality, and health-related quality of life in patients with advanced renal dysfunction.

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Section: Discussionmentioning

confidence: 92%

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

Hui¹,

Kang²,

Park³

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…Interestingly, a study by Adijiang and Niwa demonstrated that administration of AST-120 preserves renal expression of Klotho and prevents tubular cell senescence in the kidneys of chronic renal failure (CRF) rats [Adijiang and Niwa, 2010]. A decreased expression of Klotho, a protein predominantly expressed in mouse, rat and human kidneys, may play an important role in vascular calcification, arteriosclerosis and osteoporosis development.…”

Section: Ast-120 In Cvdsmentioning

confidence: 99%

The role of AST-120 and protein-bound uremic toxins in irritable bowel syndrome: a therapeutic perspective

Mosińska

Storr

Fichna

2015

Therap Adv Gastroenterol

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AST-120 (kremezin) exhibits its favourable effects in reducing the levels of renal toxins by selective adsorption of low molecular weight substances from the intestinal lumen. So far, a vast majority of studies were focused on the role of AST-120 in the treatment of chronic kidney diseases and cardiovascular disorders, and positive therapeutic effects of the agent have already been confirmed in clinical conditions. Up to the present, there are only a few studies regarding the role of AST-120 in irritable bowel syndrome (IBS). Compelling data suggest the ability of the compound to adsorb protein-bound uremic toxins and mast cell derived mediators and to modulate the farnesoid X receptor, which is a bile acid sensor indispensable for maintaining homeostasis in the intestine. In this review we focus on the actions of AST-120 on intestinal permeability, reduction of visceral sensitivity and alteration of gut motility. We also discuss whether AST-120 can mitigate common IBS symptoms, such as abdominal pain, bloating and malfunction of the colonic transit and thus improve the quality of life of patients with IBS.

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“…We demonstrated that administration of AST-120 to CKD rats significantly increased the expression of Klotho in the kidney as compared with CKD rats [20]. Recently, we reported that indoxyl sulfate administration reduced immunostaining intensity of Klotho in rat kidneys [21].…”

Section: Introductionmentioning

confidence: 99%

Indoxyl Sulfate Downregulates Renal Expression of Klotho through Production of ROS and Activation of Nuclear Factor-ĸB

Shimizu

Bolati²,

Adijiang³

et al. 2011

Am J Nephrol

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Background/Aim: Klotho, an anti-aging gene, is expressed in the kidneys, and its renal expression is decreased in chronic kidney disease (CKD). The present study aimed to examine whether renal expression of Klotho is regulated by indoxyl sulfate, a uremic toxin, using rat kidneys and human proximal tubular cells (HK-2). Methods: The effect of indoxyl sulfate on renal expression of Klotho was examined using (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive indoxyl sulfate-administered rats (DH+IS). The effects of indoxyl sulfate, inhibitors of nuclear factor-ĸB (NF-ĸB) and an antioxidant on the expression of Klotho in HK-2 cells were examined. Results: DH+IS and DN+IS rats showed decreased expression of Klotho mRNA in the kidneys as compared with DH and DN rats, respectively. Indoxyl sulfate suppressed the expression of Klotho mRNA and protein in HK-2 cells, whereas an antioxidant, N-acetylcysteine, and NF-ĸB inhibitors, pyrrolidine dithiocarbamate and isohelenin, alleviated these effects. Conclusions: Indoxyl sulfate downregulates Klotho expression in kidneys through production of reactive oxygen species and activation of NF-ĸB in proximal tubular cells. Indoxyl sulfate may be involved in reduced renal expression of Klotho in CKD.

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An Oral Sorbent, AST-120, Increases Klotho Expression and Inhibits Cell Senescence in the Kidney of Uremic Rats

Cited by 40 publications

References 32 publications

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

The role of AST-120 and protein-bound uremic toxins in irritable bowel syndrome: a therapeutic perspective

Indoxyl Sulfate Downregulates Renal Expression of Klotho through Production of ROS and Activation of Nuclear Factor-ĸB

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