Abstract 10918: AST-120 Prevents the Progression of Kidney Injury After Myocardial Infarction

Abstract

Introduction: Chronic kidney disease (CKD) is a crucial risk factor for cardiovascular disease (CVD), and combined CKD and CVD further increases morbidity and mortality. Therefore, the prevention of kidney injury is essential for the improvement of prognosis of patients with CVD. Among the many factors, increased oxidative stress plays a role for the pathogenesis of CKD and CVD. Hypothesis: AST-120, which is an oral charcoal adsorbent, may prevent kidney injury by reducing one of the uremic toxins, indoxyl sulfate (IS) and oxidative stress in a rat myocardial infarction (MI) model. Methods: At 10 weeks of age, male spontaneously hypertensive rats (SHR) were divided into 3 groups: SHR (n=6), MI (n=8) and MI+AST-120 groups (n=8) and the administration of AST-120 was started at 11 weeks of age. MI was induced by the ligation of the left coronary artery in the MI and MI+AST-120 groups at 10 weeks of age. At 18 weeks of age, rats were sacrificed, and blood and urine analyses, mRNA expression analysis, renal histological analysis, and echocardiography were performed in these groups. Results: At 18 weeks of age, though there were no significant differences in blood pressure and kidney function, serum IS levels and urinary IS excretion were reduced in the AST-120 groups compared to the MI groups. Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion, serum tissue growth factor beta (TGF-β) levels, serum neutrophil gelatinase-associated lipocalin (NGAL) levels, serum kidney injury molecular-1 (KIM-1) levels and serum,L-type fatty acid binding protein (L-FABP) levels were also decreased in the MI+AST-120 group compared to the other two groups. The mRNA expressions of NADPH oxidase and NF-kappa B, connective tissue growth factor (CTGF) in the kidney were significantly decreased in the MI+AST-120 group compared to the MI group. In vitro data using LCC-PK1 cells also supported the influence of IS on kidney injury. Further immunohistological analysis revealed that intrarenal oxidative stress was reduced by AST-120 administration. Conclusions: Our data showed that IS increased after MI and AST-120 is suggested to have protective effects on kidney injury after MI through the suppression of oxidative stress.