Long-term effects of AST-120 on the progression and prognosis of pre-dialysis chronic kidney disease: a 5-year retrospective study

Satô, Eiichi; Tanaka, Atsushi; Oyama, Jun‐ichi; Yamasaki, Ayumu; Shimomura, Mitsuhiro; Atsushi, Hiwatashi; Ueda, Yoshihiko; Amaha, Mayuko; Nomura, Motoo; Matsumura, Daiju; Nakamura, Tsukasa; Node, Koichi

doi:10.1007/s00380-015-0785-7

Cited by 17 publications

(12 citation statements)

References 25 publications

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“…One hundred twenty-eight patients received AST-120 (6 g/day), while the remaining 150 patients did not. The prevalence of dialysis induction, mortality, and cardiovascular events in patients treated with AST-120 was significantly lower after 3 and 5 years compared with the prevalence observed in the untreated patients, suggesting that long-term treatment with AST-120 may improve the prognosis of CKD patients in the predialysis stage [124,125].…”

Section: Evidence From (Pre)clinical Studiesmentioning

confidence: 88%

“…Additional evidence can be extrapolated from studies restoring the OS imbalance of kidney disease. Indeed, some interventional studies in humans suggest improvement of renal injury or creatinine clearance with the correction of the OS imbalance [79,[124][125][126][127].…”

Section: Evidence From (Pre)clinical Studiesmentioning

confidence: 99%

“…AST-120, an oral absorbent used particularly to decrease uremic toxins such as IS [124], has been commonly used in Japan to slow deterioration of renal function in patients with CKD. Sato et al studied in a retrospective analysis of 278 patients, diagnosed with CKD stages III-V, the effect of AST-120 on the need to start dialysis during 5 years.…”

Section: Evidence From (Pre)clinical Studiesmentioning

confidence: 99%

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Oxidative stress in chronic kidney disease

et al. 2018

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Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen (ROS) and nitrogen (RNS) species. When the balance is not disturbed, OS has a role in physiological adaptations and signal transduction. However, an excessive amount of ROS and RNS results in the oxidation of biological molecules such as lipids, proteins, and DNA. Oxidative stress has been reported in kidney disease, due to both antioxidant depletions as well as increased ROS production. The kidney is a highly metabolic organ, rich in oxidation reactions in mitochondria, which makes it vulnerable to damage caused by OS, and several studies have shown that OS can accelerate kidney disease progression. Also, in patients at advanced stages of chronic kidney disease (CKD), increased OS is associated with complications such as hypertension, atherosclerosis, inflammation, and anemia. In this review, we aim to describe OS and its influence on CKD progression and its complications. We also discuss the potential role of various antioxidants and pharmacological agents, which may represent potential therapeutic targets to reduce OS in both pediatric and adult CKD patients.

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Section: Evidence From (Pre)clinical Studiesmentioning

confidence: 88%

Section: Evidence From (Pre)clinical Studiesmentioning

confidence: 99%

Section: Evidence From (Pre)clinical Studiesmentioning

confidence: 99%

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Oxidative stress in chronic kidney disease

et al. 2018

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“…In patients with chronic kidney disease (CKD), elevated levels of indoxyl sulfate and p-cresyl sulfate are associated with increased risk of all-cause mortality, and p-cresyl sulfate was associated with an increased risk of cardiovascular events [12]. Administration of the oral sorbent AST-120, that prevents intestinal absorption of PBUT precursors, has been associated with a lower risk of mortality and cardiovascular events [13,14].…”

Section: Introductionmentioning

confidence: 99%

Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome

Gelder

Middel

Vernooij

et al. 2020

Toxins

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Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (−15.3 to 34.6) in patients treated with HDF and increased by 11.9% (−15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

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“…After 3 and 5 years, the incidence of dialysis induction, mortality, and cardiac and stroke events in patients who underwent AST-120 treatment was meaningfully lower ( p < 0.0001) than that of the control group. The study indicated that long-term treatment with AST-120 improves the prognosis of CKD patients at the pre-dialysis stage [ 118 ].…”

Section: Clinical Trials Involving Ast-120mentioning

confidence: 99%

Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

Liu

Tomino

2018

Toxins

140

101

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Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.

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Long-term effects of AST-120 on the progression and prognosis of pre-dialysis chronic kidney disease: a 5-year retrospective study

Cited by 17 publications

References 25 publications

Oxidative stress in chronic kidney disease

Oxidative stress in chronic kidney disease

Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome

Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

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