Myocardial infarction impairs renal function, induces renal interstitial fibrosis, and increases renal KIM-1 expression: implications for cardiorenal syndrome.

Progressive decline in renal function coexists with myocardial infarction (MI); however, little is known about its pathophysiology. This study aimed to systematically identify post-MI renal changes (functional, histological, and molecular) over time in a rat MI model and examine potential mechanisms that may underlie these changes. Rats were randomized into three groups: nonoperated, sham, and MI. Cardiac and renal function was assessed before death at 1, 4, 8, 12, and 16 wk with tissues collected for histological, protein, and gene studies. Tail-cuff blood pressure was lower in MI than sham and nonoperated animals only at 1 wk (P < 0.05). Systolic function was reduced (P < 0.0001) while heart/body weight and left ventricle/body weight were significantly greater in MI animals at all time points. Glomerular filtration rate decreased following MI at 1 and 4 wk (P < 0.05) but not at 8 and 12 wk and then deteriorated further at 16 wk (P = 0.052). Increased IL-6 gene and transforming growth factor (TGF)-β protein expression as well as macrophage infiltration in kidney cortex was detected at 1 wk (P < 0.05). Renal cortical interstitial fibrosis was significantly greater in MI animals from 4 wk, while TGF-β bioactivity (phospho-Smad2) was upregulated at all time points. The degree of fibrosis increased and was maximal at 16 wk. In addition, kidney injury molecule-1-positive staining in the tubules was more prominent in MI animals, maximal at 1 wk. In conclusion, renal impairment occurs early post-MI and is associated with hemodynamic and structural changes in the kidney possibly via activation of the Smad2 signaling pathway.