Abstract 15018: Experimental Renal Ischemia Induces Proximal Tubule CD40 Expression
Introduction: CD40 plays a crucial role in immunity and inflammation, is activated by sCD40L released from activated platelets, and induces renal fibrosis in some injury models. Our recent work in patients with atherosclerotic renal artery stenosis suggests that 1) platelet inhibition prevents ischemic renal injury, and 2) circulating CD40 predicts loss of kidney function. The mechanism linking CD40 to ischemic renal injury is not known.
Hypothesis: Renal ischemia induces renal CD40 expression.
Methods: Male Sprague Dawley rats weighing between 250-300 g were used. Western blot analysis, trichrome staining, and immunohistochemistry were performed on kidney tissue derived from two kidney one clip (2K1C) rats (n=10) four weeks following surgery. Eight sham operated animals were used as controls.
Results: The 2K1C animals exhibited a substantial increase in systolic blood pressure compared to controls (162 ± 5 vs 111 ± 1mmHg, p<0.01). Kidney tissue derived from the clipped kidneys showed a significant increase in CD40 expression compared to the unaffected contralateral kidneys and controls (Figure 1, p<0.01). The increase in CD40 expression was confirmed by immunohistochemistry, and was confined to the proximal tubule. The affected kidneys also showed a significant increase in collagen type-1 compared to the contralateral kidneys and controls (p<0.01), which was confirmed by trichrome staining.
Conclusions: Ischemic renal disease induces proximal tubular expression of CD40 providing a mechanistic link between CD40 and the development of renal injury.
- © 2013 by American Heart Association, Inc.