Research Highlights

Reducing the Incidence of Acute Kidney Injury

Charles Brooks, MD, MSc

Acute kidney injury (AKI), an independent risk factor for the development of chronic kidney disease, end-stage renal disease, and death, is a known complication of invasive procedures used in the diagnosis and treatment of cardiovascular disease. In addition to increased morbidity and mortality, AKI results in substantial increases to hospital costs.

Serum creatinine is a byproduct of muscle metabolism and an important measure of renal health. Even small increases in serum creatinine following cardiac surgery are associated with adverse outcomes; a single episode of AKI that results in a tripling of serum creatinine levels increases hospital costs by an average of $74,178. No drugs are currently approved for treatment of AKI, which has led us to ask: what are alternative methods for reducing the incidence of AKI? This clinical question propelled a multidisciplinary effort in the Division of Nephrology: the Acute Kidney Injury Risk Reduction Initiative.

We are investigating process and exposure variables for pre-, intra- and post-operative procedures, and designing risk-reduction interventions. The initiative’s preliminary outcomes data for cardiac surgery for the first three quarters since implementation of these interventions has shown a decrease in risk-adjusted incidence of AKI of one-third compared to baseline, with cost savings exceeding several hundred thousand dollars. We are continuing to develop and implement AKI risk-reduction strategies in each of the surgical service disciplines.


Modulation of Cellular Iron Dynamics to Treat Kidney Injury

Sundararaman Swaminathan, MD

Labile iron plays an important role in tissue and renal injury. As our understanding of renal iron transport at the molecular level has grown, so has the opportunity to develop novel therapeutics for kidney injury. No FDA-approved drugs exist to prevent or treat acute kidney injury (AKI). Our laboratory is taking advantage of the new knowledge available regarding iron metabolism to identify new therapeutic targets.

Low urine hepcidin levels predict AKI. Hepcidin-mediated downregulation of ferroportin leads to an increase in intracellular iron. In our first approach, we are determining the effects of therapeutic modulation of iron metabolism in models of AKI.

cellular ironEfforts to retard progression of diabetic nephropathy have met with little success. Our second major focus is defining diabetes-mediated effects on systemic and renal iron metabolism. Utilizing murine models and cell culture systems of diabetes, we are seeking to determine the effects of iron metabolism modulation on end-organ damage.

We believe these methods have the potential to be extended to treatment of human kidney disease.

Collaborators include Mark Okusa, Peter Lobo, Ariel Gomez, and Cindy Roy.