Efficacy of AST-120 in Preventing the Progression of Chronic Kidney Disease: A Meta-analysis

Chronic kidney disease (CKD) is a major cause of disease burden globally. With end-stage renal disease (ESRD), renal replacement therapy via dialysis or kidney transplant can be economically costly. This meta-analysis evaluated the efficacy of AST-120, an oral adsorbent marketed to be able to delay progression of CKD. Outcomes assessed included mortality, ESRD incidence, and doubling of serum creatinine. Databases including Cochrane, PubMed, and Clinicaltrials.gov were searched, and literature-mining from prior publications was also done, yielding a total of 50 non-duplicate citations. Further screening for appropriateness yielded 5 studies included in this meta-analysis. Regarding the effect of AST-120 on all-cause mortality among CKD patients, the pooled data showed a total of 110 events out of 1503 subjects in the interventional group and 116 events out of 1494 subjects in the control group, giving a risk ratio (RR) with 95% confidence interval (CI) of 0.94 [0.74, 1.21]. On the outcome of ESRD incidence, a total of 353 events out of 1524 subjects in the interventional group and 374 events out of 1517 subjects in the control group yielded a RR with 95% CI of 0.94 [0.83, 1.07]. Regarding doubling of serum creatinine, 155 events in both the interventional and control groups, which had 1503 and 1494 subjects, respectively, gave a RR with 95% CI of 0.99 [0.80, 1.22]. In conclusion, AST-120 has no significant clinical benefit over standard treatment in delaying CKD progression. Further studies examining different dosages of AST-120 and its effect on different CKD stages are recommended.

Effects and Safety of an Oral Adsorbent on Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis

Background: AST-120 (Kremezin), which is an oral spherical carbon adsorbent, has been reported to have the potential for retarding disease progression in patients with chronic kidney disease. We aimed to evaluate its efficacy and safety in this study. Methods: We systematically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases. The primary outcomes were the renal outcome and all-cause mortality, and the change in serum indoxyl sulfate (IS) levels. The safety outcome was also evaluated in terms of reported major adverse events. A random-effects model was used when heterogeneity was expected. Results: Eight studies providing data for 3349 patients were included in the meta-analysis. The risk ratio of renal outcome and all-cause mortality were 0.97 (95% CI: 0.88–1.07; 6 trials) and 0.94 (0.73–1.20; 5 trials), respectively. Furthermore, the weighted mean change in IS levels from baseline to the end of the study was −0.28 mg/dL (95% CI: −0.46 to −0.11; 4 trials). Conclusions: This study provides evidence that AST-120 can effectively lower IS levels but still controversial in terms of slowing disease progression and all-cause mortality. Except for dermatological events, the incidence of adverse events did not differ significantly between the AST-120 and placebo groups.

EFFICACY OF GRANULOCYTE COLONY-STIMULATING FACTOR AND ENTEROSORPTION IN MELPHALAN-INDUCED BONE MARROW SUPPRESSION IN GUERIN CARCINOMA GRAFTED RATS

Background. Side effects of antineoplastic agents (especially leukopenia and neutropenia) could be the main limiting factors for efficient treatment. Objective. The research is aimed at the study of myeloprotective capability of biosimilars of granulocyte colony stimulating factor (G-CSF) and granular carbon oral adsorbent C2 in melphalan-induced bone marrow suppression in Guerin carcinoma-grafted rats. Methods. Melphalan at the dose of 5.5 mg/kg was used to promote bone marrow suppression in the Guerin carcinoma grafted rats. To fight myelosuppression, we used filgrastim and its analogue, designed and produced by IEPOR, a recombinant granulocyte colony-stimulating factor (r-GCSF). Carbon granulated enterosorbent C2 was used for enteral sorption therapy (bulk density γ=0.18 g/cm3, diameter of granules 0.15-0.25 mm, BET pore surface – 2162 m2/g). All rats were sacrificed on the 17th day after carcinoma cells inoculation or on the 8th day after Melphalan injection. Results. Alkylating cytostatic agent caused severe leukopenia (by 95.7%), neutropenia (by 73.9%), and thrombocytopenia (by 84.9%) in the experimental rats. Mortality rate was 57%. Filgrastim and enterosorption with carbon oral adsorbent C2 increased the studied indices, but the most prominent results were observed when combination of both factors was used. Studied means did not affect the anti-tumor efficacy of Melphalan alone and in combination. Conclusions. Our results are perspective for further investigation of the efficacy of the combination of carbon oral adsorbents and hematopoietic cytokines in cases of ameliorate anti-cancer chemotherapy side effects, and its implementation into clinics.