AST-120 (Kremezin) for Chronic Kidney Disease
AST-120 (Kremezin) has demonstrated consistent reductions in circulating protein-bound uremic toxin biomarkers, especially indoxyl sulfate, but it has not shown consistent benefits on hard clinical outcomes in randomized controlled trial meta-analyses. [1], [2], [3]
Current CKD management recommendations emphasize kidney- and cardiovascular-protective therapies with established outcome benefit (including RAS inhibitors, SGLT2 inhibitors, and mineralocorticoid receptor antagonists where indicated), and AST-120 is not part of these evidence-based core treatment strategies. [4]
Mechanism of Action and Expected Biomarker Effects
AST-120 is an oral carbon adsorbent designed to reduce intestinal generation and systemic absorption of protein-bound uremic toxins. [2]
Systematic review evidence shows reduction in serum indoxyl sulfate levels with AST-120 versus placebo. [1], [3]
Clinical Efficacy for Kidney Outcomes
A meta-analysis of randomized trials found no statistically significant reduction in the risk of the composite renal outcome (risk ratio 0.97, 95% CI 0.88–1.07) and no statistically significant reduction in all-cause mortality (risk ratio 0.94, 95% CI 0.73–1.20). [1]
A separate network meta-analysis found that tailored-dose AST-120 was associated with lower event rates of end-stage renal disease (risk ratio 0.78, 95% CI 0.62–0.99) and composite renal outcomes (risk ratio 0.78, 95% CI 0.63–0.97) versus no AST-120, while mortality effects were not significant. [2]
Clinical Efficacy for Mortality
No statistically significant mortality benefit was detected in pooled randomized trial evidence (risk ratio 0.94, 95% CI 0.73–1.20). [1]
Safety and Tolerability
In randomized trial meta-analytic data, adverse events were not significantly different between AST-120 and placebo except for dermatologic events. [1]
Practical Evidence-Based Interpretation
AST-120 can lower specific biomarker targets in CKD. [1], [3]
AST-120 has not demonstrated consistent improvement in CKD progression and mortality across randomized trial meta-analyses, with some analyses suggesting benefit only under specific dosing strategies. [1], [2]
Treatment Prioritization in CKD
KDIGO-directed CKD treatment is centered on interventions with proven outcome benefit, including RAS inhibitors and SGLT2 inhibitors for appropriate patients and additional agents for selected risk profiles. [4]
AST-120 should not be used as a substitute for guideline-directed disease-modifying CKD therapies. [4]
Bottom Line
AST-120 (Kremezin) reduces indoxyl sulfate and other protein-bound uremic toxin biomarkers in CKD, but randomized trial meta-analyses have not shown consistent reductions in CKD progression outcomes or all-cause mortality, with mortality benefit not demonstrated and renal outcome benefit, when present, appearing dose-strategy dependent. [1], [2], [3]