Supported Research

Lay Abstract

The overall objective of this research proposal is to determine how the response of kidney cells to problems with protein production and folding can cause these cells to die and how we can stop this process. Death of kidney cells occurs when the kidney does not get enough blood. When the kidney does not get enough blood, we call this renal ischemia. Death of kidney cells can also occur when the kidney is exposed to harmful chemicals. Both processes cause acute kidney injury and both processes cause the proteins that make up the kidney cells to misfold and not function. This type of kidney injury involves death of cells within the kidney, which stops the kidney from working properly to filter the blood. This type of kidney injury can cause kidney failure and may be life threatening. Even if the kidneys recover from the damage they endured, this can increase the risk of developing long-term kidney disease and kidney failure later in life. Purpose: These studies will allow us to find out if correcting problems with the production of proteins in the cells that make up the kidneys will be useful to help people who are sick with kidney injury. Our data to date has suggested specific drug targets, and in these studies we will determine the validity of these targets in human kidney cells and animal models. We will also test specific drugs to see if they can prevent kidney injury in animal models. Anticipated Outcomes: We hope to validate our drug targets and find lead compounds that can be further developed as drugs to prevent kidney injury. Patient Engagement: We do not have a patient engagement plan since our work is being conducted on a molecular biological level and so does not directly involve patients. However, we feel our research to find new approaches to prevent kidney injury where no current treatments exist will benefit patients or in the best case scenario prevent people from becoming chronic kidney disease patients. Relevance to Patients/Community: Our work is relevant to patients and the community since kidney injury caused by lack of blood flow to the kidneys in a number of circumstances, including cardiac bypass surgery and dangerously low blood pressure, worsens the patients’ condition and may become life threatening. We seek to develop a way to prevent this kidney injury that, in the form of a drug, may be given to patients at risk and prevent this life threatening condition. Further, we wish to improve kidney recovery from this situation so patients do not face an increased risk of chronic kidney disease or kidney failure later in life. Conclusion: We feel we can develop unique drug targets to prevent acute kidney injury in patient populations at risk to renal ischemia. Using test compounds we feel we can further drug discovery to prevent the occurrence of this life threatening condition in those at risk and prevent some of the death and subsequent kidney disease that arises under this conditions.