Acute kidney injury (AKI) is a frequent complication in the intensive care unit with limited therapeutic modalities. Although survival from isolated AKI has improved with recent advancements in renal replacement therapy, mortality from AKI complicated by multiorgan dysfunction has remained unchanged and is estimated to be approximately 50%. Hence, defining and better understanding the pathophysiology of distant organ dysfunction associated with AKI is clinically important because it may lead to new treatment strategies. In animal models, it has become increasingly clear that AKI is not an isolated event but results in remote organ dysfunction involving the heart, lungs, liver, intestines, and brain through an inflammatory mechanism that involves neutrophil migration, cytokine expression, and increased oxidative stress. The purpose of this brief review is to summarize the human and basic science evidence for AKI and its detrimental effects on distant organs.

Extracellular superoxide dismutase (EC-SOD, EC 1.15.1.1) is a major antioxidant enzyme that is located in the extracellular matrix and on the cell surface. EC-SOD protects against cell and tissue damage initiated by extracellular-produced reactive oxygen species (ROS). We investigated a major role of EC-SOD in the development of tumor formation. In this study, we reported that skin-specific overexpressed EC-SOD transgenic mice showed half the number of tumors compared with the nontransgenic mice in the dimethylbenzanthracene (DMBA)-initiated and a 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin carcinogenesis model. This model showed a significant increase of the epidermal cell proliferation in the nontransgenic mice, but the proliferative response in the transgenic mice was delayed. The 8-hydroxy-2'-deoxyguanosine (8OH-dG) detection assay showed that the oxidative DNA damage was significantly higher in the nontransgenic mice than in the transgenic mice after TPA treatments. Overall, EC-SOD overexpression inhibited the TPA-induced cell proliferation and DNA damage, and reduced the subsequent formation of tumors. Our data suggest that EC-SOD plays a protective role in DMBA/TPA-induced skin carcinogenesis.

Severely jaundiced healthy term infants had similar rates of decrease in iSB levels during the first 4 h of intensive phototherapy, irrespective of whether they received oral or intravenous fluid supplementation. However, using the oral route avoided the need for intravenous cannulae and their attendant complications.

Despite the present lack of therapies for the treatment and prevention of acute renal failure, there are reasons to be optimistic. Recent research has led to the development of several different strategies that may provide a breakthrough in the treatment of acute renal failure.