The role of catalytic iron in acute kidney injury.

What is Catalytic (Labile) Iron, and Why is it Important? The pathologic effects of iron accumulation in tissue in iron-overload states, such as are described in patients with thalassemia, are widely known. What is new in the field is the recognition that iron plays an important role in the pathophysiology of tissue injury in the absence of systemic iron overload. Critical to iron’s importance in biologic processes is its ability to cycle reversibly between its ferrous and ferric oxidation states. This precise property, which is essential for its functions, also makes it very dangerous because free iron can catalyze the formation of free radicals (1), which can damage macromolecular components of the cell. Although iron is the most abundant transitional metal in the body, labile, or catalytic, iron, which can be measured by several methods (1,2), constitutes only a small fraction of the total iron pool. Labile iron was originally defined as a transitional pool between extracellular and cellular iron and was generally associated with low-molecular-weight chelates. From a pathophysiologic standpoint, however, an iron pool that can participate in redox cycling is important and is therefore often referred to as catalytic iron. There are two broad lines of evidence for the role of catalytic iron in the pathophysiology of disease: That it is increased in disease states and that iron chelators provide a protective effect, thereby establishing a cause– effect relationship. This has been demonstrated in a variety of disease states, including acute and chronic kidney disease, acute myocardial infarction, and neurodegenerative disorders. Thus, its role in disease processes seems to be a common theme of cellular injury.