Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation
Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba 270-0034, Japan. Metabolism: clinical and experimental
(Impact Factor: 3.89).
02/2010; 60(2):260-4. DOI: 10.1016/j.metabol.2010.01.023
AST-120 is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) and improves the prognosis of the patients under dialysis. Although tubulointerstitial injury is more important than glomerulopathy in terms of renal prognosis in patients with CRF, effect of AST-120 on tubular injury in CRF patients remains unknown. In this study, we examined whether and how AST-120 treatment could improve tubular damage in nondiabetic CRF patients. Fifty nondiabetic CRF patients were enrolled in the present study and divided into 2 groups: one was the AST-120-treated group (15 men and 10 women) and the other was the age-, sex-, and clinical variables-matched non-AST-120-treated control group. Patients were followed up for 12 months. We investigated the effects of AST-120 on serum levels of interleukin-6 (IL-6), proteinuria, and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and L-fatty acid binding protein (L-FABP), markers of oxidative stress and tubular injury, respectively. AST-120 treatment (6 g/d), but not control treatment, for 12 months significantly reduced IL-6, proteinuria, and urinary excretion levels of L-FABP and 8-OHdG, and inhibited the increase in serum creatinine in CRF patients. In univariate analyses, L-FABP levels were correlated with age, proteinuria, 8-OHdG, and IL-6. In multiple stepwise regression analysis, proteinuria and urinary 8-OHdG levels were independently related to L-FABP levels (R² = 0.605). Our present study demonstrated for the first time that AST-120 improved tubular injury in nondiabetic CRF patients. AST-120 may exert beneficial effects in CRF patients by protecting tubular damage partly via reduction of proteinuria and oxidative stress generation.
Available from: Glyn O. Phillips
- "One such approach is to administer sorbents that bind to microbial metabolites. Evidence is accumulating that the carbon-based sorbent AST-120 may reduce circulating levels of indoxyl sulfate and ameliorate decline in renal function (Iida et al., 2006; Nakamura et al., 2011; Owada et al., 2010; Ueda, Shibahara, Takagi, Inoue, & Katsuoka, 2007, 2008). This reduces the intestinal absorption of tryptophan-derived indole, which subsequently reduces the hepatic conversion of indole to indoxyl sulfate. "
Available from: Yasuhiro Hashimoto
- "In addition, Nakamura et al.  "
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ABSTRACT: The oral adsorbent AST-120 has the potential to delay dialysis initiation and improve survival of patients on dialysis. We evaluated the effect of AST-120 on dialysis initiation and its potential to improve survival in patients with chronic kidney disease. The present retrospective pair-matched study included 560 patients, grouped according to whether or not they received AST-120 before dialysis (AST-120 and non-AST-120 groups). The cumulative dialysis initiation free rate and survival rate were compared by the Kaplan-Meier method. Multivariate analysis was used to determine the impact of AST-120 on dialysis initiation. Our results showed significant differences in the 12- and 24-month dialysis initiation free rate (P < 0.001), although no significant difference was observed in the survival rate between the two groups. In conclusion, AST-120 delays dialysis initiation in chronic kidney disease (CKD) patients but has no effect on survival. AST-120 is an effective therapy for delaying the progression of CKD.
Available from: Hideki Fujii
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ABSTRACT: Cardiovascular disease (CVD) is a leading cause of death in chronic kidney disease (CKD) patients. One of the proposed mechanisms assumes that accumulated uremic toxins play an important role in the progression of CVD in CKD. Recently, it has been reported that AST-120 may attenuate progression of CVD through absorption of uremic toxins. In this study, we examined the association between the use of AST-120 and cardiac abnormalities in CKD patients.
This was a cross-sectional study of predialysis CKD patients hospitalized in our institution between April 2008 and October 2009. We divided 107 patients into two groups based on whether AST-120 had been administered for more than 6 months (AST-120 group: n = 43) or not (control group: n = 64). Echocardiography and laboratory tests were performed for all patients; we examined the relationship between clinical characteristics and cardiac abnormalities.
The number of patients with left ventricular (LV) concentric change was significantly smaller in the AST-120 group than in the control group. In multivariable analysis, the administration of AST-120, gender, and pulse pressure were significantly correlated with LV concentric change.
Our findings suggest that AST-120 prevents the development of LV concentric change in predialysis CKD patients.
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