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

Hui, Ran; Kang, Shin Wook; Park, Cheol Whee; Ryong, Dae; Na, Ki Young; Kim, Sung Gyun; Yoon, Sun Ae; Han, Sang Youb; Chang, Jae Hyun; Park, Sung Sup; Lim, Chun Soo; Kim, Yon Su

doi:10.2215/cjn.12011214

Cited by 71 publications

(68 citation statements)

References 24 publications

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“…Heart failure also increases intestinal leakiness independently of CKD 181 . Among patients with CKD, intestinal p-cresol uptake is higher in those with cardiovascular disease, independent of kidney function 182 .…”

Section: Ckd Alters the Gut-kidney Linkmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.

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Section: Ckd Alters the Gut-kidney Linkmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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“…plus routine care compared with routine care alone in patients with stages 1-5 (non-dialysis) CKD, Wu et al [54] reported that AST-120 treatment resulted in a signiicant reduction in the rate of decline in creatinine clearance (2 studies, 486 participants; standardized mean diference CKD from 11 Korean centres reported that oral administration of AST (6 g/day of AST-120 in 3 divided daily doses) did not signiicantly afect time to the primary composite outcome of doubling of serum creatinine, eGFR decrease >50%, or initiation of renal replacement therapy (HR 1.12, 95% CI 0.85-1.48) [56]. There was no signiicant diference in change in serum IS levels over time between the intervention and control group (p = 0.29).…”

Section: Gastrointestinal Sequestrationmentioning

confidence: 99%

The Roles of Indoxyl Sulphate and p-Cresyl Sulphate in Patients with Chronic Kidney Disease: A Review of Therapeutic Options

Nataatmadja¹,

Cho²,

Campbell³

et al. 2018

Chronic Kidney Disease - From Pathophysiology to Clinical Improvements

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Indoxyl sulphate (IS) and p-cresyl sulphate (PCS) are products of proteolytic bacterial fermentation by gut microbiota. They accumulate in the sera of patients with chronic kidney disease (CKD) and have been associated with CKD progression and cardiovascular and all-cause mortality. Therapeutic strategies for lowering IS and PCS include increased clearance (enhanced dialysis), gastrointestinal sequestration (oral adsorbents), reduced synthesis (dietary protein restriction, dietary ibre augmentation and pre-, pro-or synbiotics), antioxidants and organic anion transporter modulators. This review will discuss the roles of IS and PCS as therapeutic targets and examine the clinical evidence for diferent treatment options and their efects on CKD and cardiovascular disease risk. We will include our group's research with pre-, pro-and synbiotic interventions to mitigate serum uraemic toxin accumulation and modify cardiovascular and renal risk.Keywords: indoxyl sulphate, p-cresyl sulphate, uraemic toxins, chronic kidney disease, gut microbiome IntroductionThe reciprocal relationship observed between gut microbiota and chronic kidney disease (CKD) has led to the recent recognition of the 'gut-kidney axis'. Patients with CKD, including those with end-stage kidney disease (ESKD), often experience impaired uraemic toxin clearance, salt and water retention, dietary restrictions, anorexia, dysgeusia and malnutrition, © 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.which in turn leads to quantitative and qualitative alterations in gut microbiome composition (gut dysbiosis). Further efects include gut wall oedema, intestinal barrier impairment, translocation of bacteria and endotoxins across the intestinal wall and resultant systemic inlammation [1][2][3]. Gut dysbiosis may in turn lead to the production of various toxins and metabolites that contribute to uraemic toxicity, cardiovascular disease and progressive kidney scarring and failure [4][5][6]. The central role of the gut microbiome in kidney health therefore makes it an appealing therapeutic target in patients with CKD [7,8].Two key nephrovascular toxins produced by proteolytic bacterial fermentation in the gut are indoxyl sulphate (IS) and p-cresyl sulphate (PCS). IS is produced by tryptophan metabolism facilitated by Escherichia coli and Clostridium sporogenes, while PCS is generated by break down of tyrosine and phenylalanine by intestinal anaerobes, such as Clostridium diicile, Faecalibacterium prausnizii, Subdoligranulum and selected strains within the Biidobacterium and Lactobacillus genus [8]. IS and PCS are both solely produced by the gut microbiota [9][10][11][12] and accumulate in the serum of patients with CKD due to both increased intestinal production and reduced glomerular iltration and proximal tubular sec...

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“…The detailed study protocol is described elsewhere (Cha et al 2016). In brief, the study participants with advanced CKD were recruited from March 2009 to August 2010 and underwent follow-up for 36 months.…”

Section: Study Populationmentioning

confidence: 99%

“…We performed the current study to identify whether OGN was associated with MACCEs or all-cause mortality, using data from a prospective randomized controlled study, K-STAR (Kremezin STudy Against Renal disease progression in Korea) (Cha et al 2016). …”

Section: Introductionmentioning

confidence: 99%

Higher Serum Levels of Osteoglycin Are Associated with All-Cause Mortality and Cardiovascular and Cerebrovascular Events in Patients with Advanced Chronic Kidney Disease

Baek

Hui

Kang

et al. 2017

Tohoku J. Exp. Med.

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Patients with chronic kidney disease (CKD) have markedly increased rates of major adverse cardiovascular and cerebrovascular events (MACCEs) and mortality. Therefore, identifying early biomarkers predicting clinical outcomes in patients with CKD is critical. We aimed to determine whether osteoglycin, a basic component of the vascular extracellular matrix, was associated with MACCEs or all-cause mortality, using data from a prospective randomized controlled study, K-STAR (Kremezin STudy Against Renal disease progression in Korea: NCT 00860431). A total of 383 patients (mean age: 56.4 years, men/women = 252/131) with CKD stage 3 to 4 from the original trial were enrolled in the present study. We measured serum osteoglycin level and examined the impact of osteoglycin on clinical outcomes. The mean value of osteoglycin levels was 13.3 ± 9.4 ng/mL (healthy control: 5.3 ± 2.1 ng/mL). In multivariable analysis, lower levels of proteinuria and hemoglobin and higher levels of C-reactive protein were significantly associated with higher osteoglycin levels. Estimated glomerular filtration rate was not related to osteoglycin level. During a mean follow-up period of 56 months, 25 deaths, 61 MACCEs, and 76 composite outcomes (all-cause mortality or MACCEs) occurred. In the non-diabetic group, each 1-ng/mL increase in serum osteoglycin was associated with all-cause mortality and composite outcome (hazard ratio [HR] = 1.058, P = 0.031; HR = 1.041, P = 0.036). However, osteoglycin levels were not associated with mortality, MACCEs, or composite outcome in the diabetic group. Our results indicate that serum osteoglycin is a potential predictor of adverse outcomes in patients with CKD.

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

Cited by 71 publications

References 24 publications

The systemic nature of CKD

The systemic nature of CKD

The Roles of Indoxyl Sulphate and p-Cresyl Sulphate in Patients with Chronic Kidney Disease: A Review of Therapeutic Options

Higher Serum Levels of Osteoglycin Are Associated with All-Cause Mortality and Cardiovascular and Cerebrovascular Events in Patients with Advanced Chronic Kidney Disease

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