The uremic toxin adsorbent AST-120 abrogates renal injury post-MI evidenced by normalization of KIM-1 protein expression and reduced collagen turnover

Abstract

Introduction: A progressive decline in renal function is a frequent accompaniment of myocardial infarction (MI). Wehave previously shown that post-MI the uraemic toxin, indoxyl sulphate (IS), kidney injurymolecule (KIM)-1 and cardiac fibrosis are increased. In chronic kidney disease (CKD) we have reported increased IS and cardiac fibrosis; both were reduced following treatment with the oral carbonic adsorbent AST-120. However, the effect of AST-120 on renal injury post-MI has not been fully explored. Methods: MI-induced rats received either AST-120 (8% in rat chow) or were untreated (MI+Veh) for 16 weeks. Sham operated rats served as controls. Serum IS level was measured at baseline and 16 weeks. Echocardiography and glomerular filtration rate (GFR) was assessed prior to sacrifice at 16 weeks. Tissues were assessed for changes using immunohistological and western blot methods. Results: Heart: Ejection fraction and fractional shortening were reduced by 39% and 49% post-MI respectively (P< 0.001 vs. sham).Cardiac collagen I andTIMP-1 expression was elevated post-MI (10 and 5 fold respectively, P< 0.01) and following AST-120 treatment reduced back to sham levels (P< 0.01). No change in MMP-2 expression was detected; and no difference observed in blood pressure betweenMI groups. Kidney:MI+Veh increased delta serum IS levels, renal fibrosis and KIM-1 expression; and reduced GFR (P< 0.05 vs sham). Compared to MI+Veh, AST-120 treatment reduced serum IS, renal fibrosis and KIM-1 expression (P< 0.05). KIM-1 expression positively correlated with serum IS levels (r= 0.56; P= 0.002). Conclusions: AST-120 reduced cardiac collagen by suppressing TIMP-1 expression. KIM-1 appears to be a sensitive renal biomarker for post-MI kidney that may be influenced by elevated IS levels. AST-120 treatment post-MI improves renal fibrosis and normalises KIM-1 and IS levels. Thus AST-120 has beneficial cardiac and renal effects post-MI, and may be a potential treatment for cardiorenal syndrome.