Grant: Operating Grant

High blood pressure is the single most important cause of kidney disease. So we need to understand how the kidney normally is protected from episodes of high blood pressure. In relation to their size the two kidneys have the highest blood flows in the body. A human kidney contains a million functional units called nephrons. Each nephron consists of a glomerulus, the tiny filter where fluid is removed from blood, and the tubule that leads fluid away. The glomerulus is a delicate structure and must be protected from episodes of high blood pressure that occur routinely in all of us. Humans and other animals have a process that adjusts the caliber of the small blood vessels that feed the glomeruli. The process is called autoregulation because it occurs entirely within the kidney. It stabilizes kidney blood flow and pressure at the glomerulus when blood pressure varies. Typically it is thought that autoregulation at each glomerulus acts independently. However, neighboring nephrons (about 20 in a cluster) exchange information and tend to work together. We suspect that these interactions are important to the effectiveness of autoregulation but we really know very little about them. We acquire images of perfusion at the surface of the kidney and analyze them to examine the signatures left when autoregulation is active. This will tell us how important it is for the nephrons in a cluster to work together. We will define how big the cluster is and how its size varies under normal conditions. Then we will use several experimental tricks to change the number of nephrons in the cluster. We expect that autoregulation provides better protection when nephrons act together. We are well placed to perform these studies because we have expertise in the subject and a long-standing interest in autoregulation. We were the first to define the problem and how to address it. We have a team made up of a physiologist, a kidney doctor, and an engineer who specializes in data analysis.