BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease (CVD). Increased oxidative stress plays a role in the pathogenesis of CVD in CKD patients. The oral charcoal adsorbent AST-120 attenuates the progression of CKD possibly by removing uraemic toxins such as indoxyl sulfate (IS), and reduces oxidative stress. We investigated the relationship between oxidative stress and cardiac damage in CKD and its prevention by AST-120. METHODS: Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed. RESULTS: At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 +/- 0.28 mL/min versus 1.60 +/- 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 +/- 0.46 mL/min versus 0.75 +/- 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores. CONCLUSIONS: Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.
BACKGROUND:Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease (CVD). Increased oxidative stress plays a role in the pathogenesis of CVD in CKDpatients. The oral charcoal adsorbent AST-120 attenuates the progression of CKD possibly by removing uraemic toxins such as indoxyl sulfate (IS), and reduces oxidative stress. We investigated the relationship between oxidative stress and cardiac damage in CKD and its prevention by AST-120. METHODS: Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed. RESULTS: At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 +/- 0.28 mL/min versus 1.60 +/- 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 +/- 0.46 mL/min versus 0.75 +/- 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores. CONCLUSIONS: Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.
Authors: Adrienne Tin; Robert Scharpf; Michelle M Estrella; Bing Yu; Megan L Grove; Patricia P Chang; Kunihiro Matsushita; Anna Köttgen; Dan E Arking; Eric Boerwinkle; Thu H Le; Josef Coresh; Morgan E Grams Journal: J Am Soc Nephrol Date: 2017-07-18 Impact factor: 10.121
Authors: Fellype C Barreto; Daniela V Barreto; Sophie Liabeuf; Natalie Meert; Griet Glorieux; Mohammed Temmar; Gabriel Choukroun; Raymond Vanholder; Ziad A Massy Journal: Clin J Am Soc Nephrol Date: 2009-08-20 Impact factor: 8.237