Renal IRI is the most common form of acute kidney injury and has been studied extensively. As an experimental model, this has a translational focus for transplant nephrology and is a useful model to study cellular responses to IRI. IRI is characterized by tubular swelling, cell death (apoptosis and necrosis), mitochondrial dysfunction, inflammatory responses, and deregulated vascular function.46 Microvascular and tubular components of the kidney have mutual, as well as unique, responses to IRI, which contribute to decreased kidney function. Given that IRI is potentially reversible, MPM can be used to image these cellular processes and then determine the success, or failure, of novel interventions. Recently, Hall and colleagues14 have used MPM to demonstrate the role of redox alterations occurring as a result of IRI. By using endogenous NADH fluorescence, mitochondrial selective probes (TMRM), ROS-sensitive dyes [dihydroethidium (DHE)], and glutathione indicators, they have shown that IRI mainly affects the distribution of mitochondria in the proximal tubular epithelium, with increased superoxide levels. Although increased ROS have been implicated in the pathophysiology of IRI before, MPM has allowed direct visualization of ROS in conjunction with cell damage. MPM image analysis of IRI during two models of kidney transplantation has revealed cast formation in the tubular profiles, mainly from increased tubular injury, necrosis, and apoptosis.51 This study also assessed the efficacy of p53 siRNA during rodent kidney transplantation and found that it significantly improved kidney function and decreased cast formation, perhaps by increasing blood flow through the vasculature.