Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea

BACKGROUND: We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD). METHODS: We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment. RESULTS: The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046). CONCLUSION: Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.

AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

Effects of Oral Adsorbent AST-120 (Kremezin(R)) on the Progression of Chronic Kidney Disease / 대한신장학회지

PURPOSE: AST-120 is known to delay progression of chronic kidney disease (CKD) when combined with other proven therapy. AST-120 is an oral adsorbent for uremic toxin, such as indoxyl sulfate from the gastrointestinal tract. There have been a lot of studies to show its effect in other countries, but there are few studies done in Korea yet. METHODS: 195 patients were included in the study (mean age, 64+/-14 years; diabetes mellitus (DM), 104 patients; male, 130 patients). The patients with CKD who started AST-120 and maintained the medication for at least 6 months were enrolled. The patients' laboratory results for 6 months before and after administrating AST-120 was surveyed. Then the rate of patients' renal functional deterioration was compared before and after AST-120. In addition, adverse effects during the medication were surveyed. RESULTS: There were no statistically significant differences in laboratory data between before and after AST-120 administration. But, after administrating AST-120, the renal deterioration slope has blunted significantly from -0.0123+/-0.0318 to -0.0013+/-0.0184 dL/mg/month (p<0.01) in 1/sCr and from -1.1423+/-2.3906 to 0.0639+/-1.3825 ml/min/1.73m2/month (p<0.01) in estimated glomerular filtration rate (eGFR). There were no differences between DM and non-DM patients in the effect of AST-120, as well as ages over 70 and below 70. There were no serious adverse effects during medication. CONCLUSION: This study showed that AST-120 had additive effect on retarding the CKD progression when combined with established therapy regardless of DM and ages without serious adverse effects.