Circulating pro-apoptotic mediators in burn septic acute renal failure

We still have no uniform concept of the pathogenesis of septic acute kidney injury (AKI). While renal hypoperfusion is the predominant factor in hypodynamic states, neither systemic nor intrarenal vasomotor changes seem to be the sole contributor to AKI in sepsis. Inflammatory and procoagulatory mediators likely play an additional role. Yet, how they exactly injure the kidney is not well understood. Septic AKI occurs without obvious inflammatory infiltrates, vascular thrombosis and tubular cell necrosis.The elegant study of Mariano and coworkers [1] in this issue of Critical Care shows that acute renal failure in septic burn patients is characterized by proteinuria, attributable to both glomerular and tubular damage. The severity of proteinuria correlated with systemic inflammatory and procoagulatory markers, and with impairment of renal function and non-survival. In a series of in vitro experiments they demonstrated that circulating factors reduced the viability and function of tubular cells and podocytes, and caused upregulation of several pro-inflammatory and pro-apoptotic genes and proteins, and down-regulation of apoptosis inhibitors. Pro-apoptotic effects were not attributable to antibiotic or uremic toxicity, but were partially attributable to endotoxin. Sepsis and burns had additive effects on tubular apoptosis. A possible mediator of these circulating pro-apoptotic effects may have been tumor necrosis factor (TNF), which was detected in burn septic acute renal failure plasma.Cells either die from necrosis or from apoptosis. While necrosis results from energy depletion, apoptosis consumes energy and is triggered by the upregulation of genes. These genes encode proteins involved in several biochemical pathways that cause cell shrinkage, condensation of chromatin, damage to cell membranes and nuclear fragmentation. Apoptosis is crucial for tissue homeostasis, tumor surveillance and immune function. Nature allows inhibition of apoptosis at several stages in the