Efficacy of AST-120 for Patients With Chronic Kidney Disease: A Network Meta-Analysis of Randomized Controlled Trials.

Pei-Yu Su,Ya-Han Lee,Chiehfeng Chen,Li-Na Kuo,Yen-Cheng Chen,Elizabeth H Chang,Yi-No Kang

doi:10.3389/fphar.2021.676345

Pei-Yu Su, Ya-Han Lee + Show 5 more

Open Access

https://doi.org/10.3389/fphar.2021.676345

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Abstract

AST-120, an oral spherical activated carbon, may delay the need for kidney dialysis and improve uremia symptoms because it can adsorb acidic and basic organic compounds, especially small-molecule uremic toxins. However, previous studies produced no conclusive evidence regarding the benefits of AST-120 in delaying the progression of chronic kidney disease (CKD). Therefore, this systematic review and network meta-analysis evaluated the effects of AST-120 in patients with CKD. Related keywords of CKD and AST-120 were used to search four databases to obtain potential evidence on this topic, and two authors individually completed evidence selection, data extraction, and quality assessment. Network meta-analysis was performed for mortality, end-stage renal disease, composite renal outcomes, and laboratory outcomes based on a frequentist approach. In total, 15 randomized controlled trials (n = 3,763) were included in the present synthesis, and the pooled results revealed non-significant differences in mortality among the treatment strategies. Low- and high-dose AST-120 were not superior to no AST-120 treatment regarding renal outcomes. However, the event rates of end-stage renal disease (risk ratio [RR] = 0.78, 95% confidence interval [CI] = 0.62–0.99) and composite renal outcomes (RR = 0.78, 95% CI: 0.63–0.97) were significantly lower in the tailored-dose AST-120 group than in no AST-120 group. The results did not reveal a small-study effect on the outcomes. Tailored dosing of AST-120 appeared to represent an optimal treatment strategy because it resulted in lower rates of composite renal outcomes and end-stage renal disease.

Highlights

Chronic kidney disease (CKD) is a direct cause of morbidity and mortality and a risk factor for cardiovascular disease, illustrating its significant effect on global health
The present study identified 3,327 references in the Cochrane Database of Systematic Reviews (i 107), Embase (i 1,689), PubMed (i 1,067), and Web of Science (i 464)
1774 references were reviewed for eligibility, and 1724 references were eliminated because of a lack of relevance (i 1,576), the inclusion of non-human cohorts (i 79), the inclusion of non-CKD populations (i 2), and a study type other than randomized controlled trial (RCT) (i 67)

Summary

Introduction

Chronic kidney disease (CKD) is a direct cause of morbidity and mortality and a risk factor for cardiovascular disease, illustrating its significant effect on global health. CKD, as a direct cause of impaired kidney function and cardiovascular disease, is responsible for 23.5 million disability-adjusted life-years 22.2–28.9) and 1.4-million cardiovascular disease-related deaths (95% UI 1.2–1.6). CKD progression increases healthcare expenditures because patients with end-stage renal disease eventually require dialysis or kidney transplantation. Early detection and appropriate treatment of CKD are important for both patients and clinicians in clinical practice. Lifestyle modification, and conventional drug treatment are used to prevent progression to end-stage renal disease or death, these strategies may not effectively control CKD. No approved therapies currently target control of uremic toxins, which may have a role in CKD progression. No approved therapies currently target control of uremic toxins, which may have a role in CKD progression. (Lau et al, 1979; Solerte et al, 1987; Kidney Disease Outcomes Quality Initiative, 2004)

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