Effect of Repeated Oral Administrations of the Oral Adsorbent AST-120 on Serum Creatinine and Other Markers of Renal Function

Marier, Jean‐François; Lee, James; Kambhampati, Siva Rama Prasad; Galitz, Lawrence; Vargas, Ramón; Moberly, James B.; Salazar, Daniel E.

doi:10.1159/000092242

Cited by 17 publications

(26 citation statements)

References 19 publications

(13 reference statements)

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“…level, whichever occurred first. Because an earlier study of AST-120 found no significant differences between AST-120-treated and placebotreated patients in 24-hour urinary creatinine excretion and sCr, 31 indicating that inconsequential or no amounts of creatinine were adsorbed by AST-120 in the gut, sCr was determined to be a valid measure of renal function in patients treated with AST-120, and an increase in sCr was selected as a component of the composite end point. The secondary end point was a quadruple composite of the primary end point and death.…”

Section: Assessments and Outcomesmentioning

confidence: 99%

Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD

Schulman

Berl

Beck

et al. 2015

Journal of the American Society of Nephrology

220

186

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Reduced GFR in patients with CKD causes systemic accumulation of uremic toxins, which has been correlated with disease progression and increased morbidity. The orally administered spherical carbon adsorbent AST-120 reduces systemic toxin absorption through gastrointestinal sequestration, which may slow disease progression in these patients. The multinational, randomized, double-blind, placebocontrolled Evaluating Prevention of Progression in CKD (EPPIC)-1 and EPPIC-2 trials evaluated the effects of AST-120 on the progression of CKD when added to standard therapy. We randomly assigned 2035 adults with moderate to severe disease (serum creatinine at screening, 2.0-5.0 mg/dl for men and 1.5-5.0 mg/dl for women) to receive either placebo or AST-120 (9 g/d). The primary end point was a composite of dialysis initiation, kidney transplantation, and serum creatinine doubling. Each trial continued until accrual of 291 primary end points. The time to primary end point was similar between the AST-120 and the placebo groups in both trials (EPPIC-1: hazard ratio, 1.03; 95% confidence interval, 0.84 to 1.27; P=0.78) (EPPIC-2: hazard ratio, 0.91; 95% confidence interval, 0.74 to 1.12; P=0.37); a pooled analysis of both trials showed similar results. The estimated median time to primary end points for the placebo groups was 124 weeks for power calculations, but actual times were 189.0 and 170.3 weeks for EPPIC-1 and EPPIC-2, respectively. Thus, disease progression was more gradual than expected in the trial populations. In conclusion, the benefit of adding AST-120 to standard therapy in patients with moderate to severe CKD is not supported by these data. 26: 173226: -174626: , 201526: . doi: 10.1681 CKD, defined as kidney damage or a GFR,60 ml/min per 1.73 m 2 for $3 months, 1 is associated with increased risk for cardiovascular events, hospitalization, and death 2 and is a global public health problem. A meta-analysis of population-based studies from 40 countries and regions reported a 6.3% overall prevalence of CKD stages 3-5 (,60 ml/min per 1.73 m 2 ). 3 Furthermore, approximately 1870 cases of ESRD per million population were reported in 2010 compared with 1355 per million in 2000, 4 underscoring the need for treatments to slow or prevent the progression of CKD. J Am Soc NephrolEarly management of CKD is recommended to reduce cardiovascular events and additional complications of decreased GFR, improve quality of life, and prolong survival. 5 Current guidelines focus on managing factors that can hasten CKD progression, such as hypertension and diabetes. 6-8 Although angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) slow the progression of CKD, especially in patients

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Section: Assessments and Outcomesmentioning

confidence: 99%

Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD

Schulman

Berl

Beck

et al. 2015

Journal of the American Society of Nephrology

220

186

View full text Add to dashboard Cite

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“…AST-120 takes the form of spherical particles, 0.2-0.4 mm in diameter, composed predominantly of porous carbon material with a high surface area, exceeding over 1600 m 2 /g [Marier et al 2006]. The abundant porosity and its wide distribution provide an extensive and efficient binding surface, which enables selective adsorption and removal of low molecular weight substances from the intestinal lumen.…”

Section: Introductionmentioning

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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“…One concern is that changes in serum creatinine associated with the use of AST‐120 are due to adsorption of creatinine from the gut as opposed to an impact on renal function. However, a recent study evaluated whether the adsorption of creatinine with AST‐120 in the gut would acutely alter creatinine balance, which would limit the meaningfulness of serum creatinine as a measure of disease progression 32 . The study used a two‐way crossover design and found no significant differences in serum creatinine or 24‐h urine creatinine with AST‐120 (9 g/day) versus placebo, thereby indicating that serum creatinine is a valid measure of changes in renal function.…”

Section: Discussionmentioning

confidence: 99%