The pathogenesis of septic acute kidney injury (AKI) is not well understood. In the present issue of Critical Care, the combined clinical and experimental study from Mariano's group provides new insight into the disease. The study shows that plasma from septic burn patients with acute renal failure initiated pro-apoptotic effects and functional alterations in renal tubular cells and podocytes in vitro that correlated with the degree of proteinuria and renal dysfunction. Pro-apoptotic effects were not attributable to antibiotic or uremic toxicity, but were partially attributable to endotoxin. Sepsis and burn had additive effects. Apart from increasing our understanding of the pathogenesis of septic AKI, the study justifies further research on therapeutic interventions in several directions. These include the binding and elimination of the source of endotoxin by selective decontamination of the digestive tract, the blocking of apoptotic pathways, or the extracorporeal removal of circulating toxic mediators using high permeability hemofiltration or coupled plasma filtration and absorption.