Akizawa 2009
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Country: Japan
Study design: randomized controlled trial
Number: treatment group (231), control group (229)
Duration: 56 weeks
Chronic kidney disease stage of treatment group subjects: 3 or lower
(21%), 4 (47%), 5 (32%)
Chronic kidney disease stage of control group subjects: 3 or lower
(20%), 4 (53%), 5 (27%)
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Outpatient
20 years or older at the time of consent to participate in the study
Serum creatinine level of 5.0 mg/dL or less at the time of case
registration
Inverse serum creatinine (calculated by using measurements at ≥ 4
times during an observation period that occurred within 48 weeks of
case registration) that is decreasing on average, determined by using
linear regression analysis
Blood pressure that is well controlled before the initial serum
creatinine measurement during the observation period
Treatment with an angiotensin-converting enzyme inhibitor and/or
angiotensinogen II receptor blocker before the initial serum
creatinine measurement during the observation period
Receipt of low-protein diet therapy (protein < 0.8 g/kg/d)
before the initial serum creatinine measurement during the observation
period
No change in type or dose of medication for kidney disease during the
4 weeks before case registration
Participant has been informed about the purpose, description, expected
adverse effects, and risks of this study according to the consent form
and has voluntarily signed the informed consent form
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Presence of obstructive disorder of the gastrointestinal tract
(constipation, ileus, and so on)
Treatment with AST-120 within the period from the initial serum
creatinine measurement before case registration to the time of study
commencement
Presence of rapidly progressive glomerular nephritis, hydronephrosis,
obstructive uropathy, drug-induced nephropathy, or transplanted kidney
Presence of such complications as severe hepatopathy, liver cirrhosis,
severe infection, class III or higher New York Heart Association
congestive heart failure, severe arrhythmia, or unstable angina
Occurrence of cardiac infarction, cerebral infarction, or cerebral
hemorrhage within the past 6 months
Presence of severe nephrotic syndrome (serum albumin < 2
g/dL)
Pregnancy or planning to become pregnant during the study period
Alcohol abuse
Body weight less than 80% or more than 160% of the standard weight
([height (m)]2 x 22)
Significant difficulty with control of blood glucose levels within 3
months of case registration (hemoglobin A1c > 8.0% on 1
occasion)
Presence of progressive malignant tumor
Unavailable for study visits at least once per 2 months to provide
urine samples
Presence of other reasons that made participation in the study
inappropriate, as determined by an investigator
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Treatment group: AST-120 6 g/d (3 divided doses) + conventional
treatment
Control group: conventional treatment
Conventional treatment: low protein diet (protein < 0.8
g/kg/d) + angiotensin-converting enzyme inhibitor or angiotensinogen
II receptor blocker
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Incidence of end-stage renal disease
Mortality rate
Doubling or serum creatinine
Adverse events
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Cha 2016
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Country: South Korea
Study design: randomized controlled trial
Number: treatment group (289), control group (290)
Duration: 36 months
Chronic kidney disease stage of control group subjects: 3 (29.3%), 4
(70.7%)
Chronic kidney disease stage of treatment group subjects: 3 (26.5%),
4 (73.5%)
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Provided informed consent
Aged ≥18 years
Followed over 6 months by nephrologists
Chronic kidney disease stage 3 or 4
Expected estimated glomerular filtration rate decline of ≥2.5 ml/min
per 1.73 m2 over 6 months or ≥5 ml/min per 1.73 m2 over 12 months
Had controlled blood pressure
No significant changes in the medical treatment for chronic kidney
disease
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Taken ketosteril or AST-120 within the last 2 months
Gastrointestinal disease, such as an active ulcer or inflammatory
bowel disease
Obstructive uropathy or other reversible kidney diseases
Autosomal dominant polycystic kidney disease
Proteinuria ≥10 g/d
Received a kidney transplantation
Moderate to severe heart failure, uncontrolled arrhythmia, or unstable
angina
Active infections or uncontrolled inflammatory diseases
Liver cirrhosis (Child-Turcotte-Pugh class B or C)
Progressive malignancy
Cerebral infarction or hemorrhage within the last 6 months
Uncontrolled blood sugar level (hemoglobin A1c ≥10.0%)
Severe anemia (hemoglobin ≤7.0 g/dl)
Life expectancy ≤12 months
Pregnant, lactating, planning to be pregnant during study period
Determined by the investigators to be inappropriate participants
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Treatment group: AST-120 6.0 g/day (3 divided doses) + routine
treatment
Control group: routine treatment
Routine treatment: standard care including angiotensin-converting
enzyme inhibitor or angiotensinogen II receptor blocker and lipid
modifiers, low-salt and low-protein diet
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Doubling of serum creatinine
50% reduction in glomerular filtration rate
End-stage renal disease requiring renal replacement therapy
Urinary protein excretion
All-cause mortality
All-cause hospitalization
Quality-of-life assessment
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Konishi 2008
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Country: Japan
Study design: randomized controlled trial
Number: treatment group (6), control group (10)
Mean duration of follow up: 37 months (control group), 34 months
(treatment group)
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Persistent positive test for urinary protein or > 300
mg/g creatinine of albumin in a spot urine
Having type 2 diabetes mellitus
Serum creatinine < 1.5 mg/dL
24-h urinary protein excretion > 0.5 g/day
No history of cardiovascular diseases
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Those not satisfying inclusion criteria
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Treatment group: AST-120 6.0 g/day + conventional treatment
Control group: conventional treatment
Conventional treatment: blood pressure, lipid, glycemic control
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Incidence of end-stage renal disease (hemodialysis initiation)
Incidence of serum creatinine exceeding 2 mg/dL
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Schulman 2015 (EPPIC-1)
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Multi-center
Study design: randomized controlled trial
Number: treatment group (510), control group (510)
Median duration: 102.1 weeks (treatment group), 103.3 weeks (control
group)
Chronic kidney disease stage of subjects in treatment group: 3a (1%),
3b (18.8%), 4 (62%), 5 (18.2%)
Chronic kidney disease stage of subjects in control group: 3a (0.2%),
3b (15.3%), 4 (69.3%), 5 (15.1%)
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Age ≥18 years
Moderate to severe chronic kidney disease
Proteinuria or progressive decline of renal function
Expected not to require renal replacement therapy for 6 months after
trial
Stable blood pressure in the past 3 months
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Uncontrolled hypertension
Obstructive or reversible kidney disease
Nephrotic syndrome (urine protein/urine creatinine 6.0)
Adult polycystic kidney disease
Uncontrolled arrhythmia or severe cardiovascular disease
Immunosuppressive therapy within 3 months
Accelerated or malignant hypertension within 6 months
History of any of the following: kidney transplantation,
malabsorption, inflammatory bowel disease, hiatal hernia, active
peptic ulcer, and severe gastrointestinal dysmotility not attributable
to the use of a phosphate binder
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Treatment group: AST-120 9.0 g/day (ten 300-mg capsules thrice daily
with meals) + routine treatment
Control group: placebo (ten 300-mg capsules thrice daily with meals) +
routine treatment
Routine treatment: not specified
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Incidence of death
Incidence of end-stage renal disease
Incidence of doubling of serum creatinine
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Schulman 2015 (EPPIC-2)
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Multi-center
Study design: randomized controlled trial
Number: treatment group (508), control group (507)
Median duration: 96.3 weeks (treatment group), 91.6 weeks (control
group)
Chronic kidney disease stage of subjects in treatment group: 3a
(0.6%), 3b (16.6%), 4 (66.2%), 5 (16.6%)
Chronic kidney disease stage of subjects in control group: 3a (0.4%),
3b (11.7%), 4 (69.2%), 5 (18.7%)
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Age ≥18 years
Moderate to severe chronic kidney disease
Proteinuria or progressive decline of renal function
Expected not to require renal replacement therapy for 6 months after
trial
Stable blood pressure in the past 3 months
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Uncontrolled hypertension
Obstructive or reversible kidney disease
Nephrotic syndrome (urine protein/urine creatinine 6.0)
Adult polycystic kidney disease
Uncontrolled arrhythmia or severe cardiovascular disease
Immunosuppressive therapy within 3 months
Accelerated or malignant hypertension within 6 months
History of any of the following: kidney transplantation,
malabsorption, inflammatory bowel disease, hiatal hernia, active
peptic ulcer, and severe gastrointestinal dysmotility not attributable
to the use of a phosphate binder
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Treatment group: AST-120 9.0 g/day (ten 300-mg capsules thrice daily
with meals) + routine treatment
Control group: placebo (ten 300-mg capsules thrice daily with meals) +
routine treatment
Routine treatment: not specified
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Incidence of death
Incidence of end-stage renal disease
Incidence of doubling of serum creatinine
Quality-of-life assessments
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Yorioka 2008
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Country: Japan
Study design: randomized controlled trial
Number: treatment group (15), control group (13)
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Adult patients 20-80 years old
Chronic kidney disease stage 3-4
Etiology of chronic kidney disease: chronic glomerulonephritis,
diabetic nephropathy, nephrosclerosis
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Age <20 or >80 years
Other underlying kidney diseases
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Treatment group: AST-120 6.0 g/day + routine treatment
Control group: routine treatment
Routine treatment: low protein diet + renin-angiotensin-aldosterone
system blocker therapy
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Incidence of end-stage renal disease
Change in glomerular filtration rate
Change on slope of glomerular filtration rate curve
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