Abstract 17765: The Uremic Toxin Adsorbent AST-120 Abrogates Renal Injury Post-Myocardial Infarction Evidenced By Bormalization Of Kidney Injury Molecule-1 Protein Expression
Introduction: An accelerated progressive decline in renal function is a frequent accompaniment of myocardial infarction (MI). We have previously shown that the kidney injury molecule (KIM)-1 is up-regulated post-MI. The uremic toxin, indoxyl sulfate (IS), is increased in chronic kidney disease (CKD); levels can be reduced by administration of the oral adsorbent AST-120, which has been shown to reduce pathological renal fibrosis in CKD. However, the effect of AST-120 on renal injury post-MI has not been fully explored.
Methods: MI-induced Sprague-Dawley rats were randomized to receive either AST-120 (dose 8% in rat chow) (n=14) or were untreated (MI+Veh; n=14) for 16 weeks. Sham operated rats (n=13) 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 pathological changes using histological and immunohistochemical methods.
Results: Ejection fraction and fractional shortening was reduced by 39% and 49% respectively (P<0.001), and isovolumetric relaxation time was increased by 31% (P<0.05) in MI +Veh animals vs. sham. Compared to sham, MI+Veh animals demonstrated an increase in the number of KIM-1 positively stained tubules (Sham 10.8 ± 2.2, MI+Veh 22.4 ± 4.5, P<0.05), increased percentage area of renal interstitial renal fibrosis (Sham 1.88 ± 0.13, MI+Veh 3.99 ± 0.18, P<0.001), increased the difference in endpoint and baseline serum IS levels by 2.2 fold (P<0.05) and reduced GFR. AST-120 reduced serum IS (P<0.001), renal KIM-1 expression (MI+AST-120 6.1 ± 1.4, P<0.05) and renal interstitial fibrosis (MI+AST-120 3.47 ± 0.21, P<0.05) compared to MI+Veh animals. KIM-1 expression was positively correlated with serum IS levels (r=0.56; P=0.002). There was no difference in blood pressure or infarct size between MI groups.
Conclusions: The injury marker KIM-1 appears to be a sensitive renal biomarker for post-MI kidney effects that may be influenced by elevated IS levels. Treatment with AST-120 post-MI improves renal interstitial fibrosis and normalizes expression of KIM-1, in association with reduced IS levels. Thus, reduction of IS by AST-120 has beneficial renal effects post-MI.
- © 2012 by American Heart Association, Inc.