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Kidney Int. 2008 Oct;74(8):1017-25. doi: 10.1038/ki.2008.346. Epub 2008 Jul 16.

Pre-existing renal disease promotes sepsis-induced acute kidney injury and worsens outcome.

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National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1268, USA.


While it is known that risk of death from sepsis is higher in patients with pre-existing chronic kidney disease its mechanism is unknown. To study this we established a two-stage mouse model where renal disease was first induced by folic acid injection followed by sub-lethal cecal ligation and puncture to induce sepsis. Septic mice with pre-existing renal disease had significantly higher mortality, serum creatinine, vascular permeability, plasma vascular endothelial growth factor (VEGF) levels, bacteremia, serum IL-10, splenocyte apoptosis and more severe septic shock when compared to septic mice without pre-existing disease. To evaluate the contribution of vascular and immunological dysfunction, we treated the folate-septic mice with soluble Flt-1 to bind VEGF and chloroquine to reduce splenocyte apoptosis. These treatments together resulted in a significant improvement in kidney injury, hemodynamics and survival. Our study shows that the sequential mouse model mimics human sepsis frequently complicated by pre-existing renal disease and might be useful in evaluating preventive and therapeutic strategies.

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