**7.2 Key notes**

An increase in LPS-induced TNFα and TNFR1 directly damages the glomerular endothelial cell fenestrae and the glomerular endothelial surface layer [8]. We have shown that not only does LPS-induce AKI in mice, but the serum of mice injected with LPS also contains cytotoxic milieu that can directly cause renal epithelial cell death [51, 52]. Overall, these studies suggest that LPS-induced AKI can be an effect of direct activity of LPS on renal parenchyma and in parallel the SIRS like condition can result in cytokine driven renal parenchymal damage to collectively worsen outcomes. Given the dependency of this model on above mentioned variables, emphasis on the importance of testing in multiple, different animal models prior to advancing therapeutic agents into clinical trials is warranted.
