Abstract 5261: Myocardial Infarction Impairs Renal Function, Induces Renal Interstitial Fibrosis and Increases Kim-1 Expression: Implications for the Cardiorenal Syndrome
Introduction: Accelerated progressive decline in renal function has been described as a coexistent event post-myocardial infarction (MI) (cardiorenal syndrome, CRS). We hypothesized that MI has early detrimental effects on the kidney by evaluating functional, structural and molecular changes over time.
Methods: Male Sprague-Dawley rats were randomized to three groups: non-operated, sham and MI. Cardiac and renal function was assessed prior to sacrifice at 4, 8, 12 and 16 weeks. Tissues were assessed for injury markers and pathological changes using histological methods and real-time PCR.
Results: Myocardial infarct size and blood pressure (BP) were the same in all groups. Percent fractional shortening was reduced in MI animals at all time points by up to 63% at 16 weeks. As expected, heart/body weight (BW) and left ventricle/BW were significantly greater in MI than sham animals. Glomerular filtration rate (GFR) was significantly decreased in MI compared to sham at 4 wks (p=0.016) but not at 8 and 12 wks; and deteriorated further at 16 wks (p=0.052). Renal cortical interstitial fibrosis and TGF-β bioactivity (p-smad2) were significantly greater in MI animals at all time points. The degree of fibrosis progressively increased and was maximal at 16 weeks. TGF-β1 gene expression in the kidney cortex trended toward an increase at 4 and 8 weeks (p=0.109 and 0.070, respectively). In addition, Kim-1 positive staining in the tubules was more prominent in MI animals over time.
Conclusions: CRS occurs early post-MI and is associated with progressive renal interstitial fibrosis via activation of Smad2 signaling pathway. Kim-1 may represent an early marker of post-MI kidney injury.