Catalytic (Labile) Iron in Kidney Disease

Despite advances in understanding the pathophysiology of acute kidney injury and chronic kidney disease, treatment for kidney disease remains unsatisfactory. The labile iron pool consists of chemical forms that can participate in redox cycling, and is therefore often referred to as catalytic iron. There are two broad lines of evidence for the role of labile iron in disease states: that it is increased in disease states, and that iron chelators provide a protective effect, thus establishing a cause—effect relationship. We summarize the importance of labile iron in several models of acute kidney injury including rhabdomyolysis, gentamicin, and cisplatin-induced acute kidney injury. In addition, we review evidence for the role of catalytic iron in inflammatory and non-inflammatory models of experimental glomerular disease as well as models of progressive kidney disease. We finally provide some preliminary human data indicating that the extensive experimental observations in experimental models may be relevant to human disease. This focus on iron is particularly relevant because of the availability of iron chelators to potentially provide new therapeutic tools to prevent and/or treat kidney disease. Randomized clinical trials are needed to evaluate the safety and efficacy of iron chelators in the treatment of acute and chronic kidney disease.