Studies in Renal Hemodynamics

The principal functional unit of the kidney is the nephron, a capillary tuft connected to a renal tubule. There are about 1 million nephrons in the human kidney, and a significant fraction of these may be closely coupled through the microvasculature. Through computational and analytical methods, two major research questions will be addressed: how does coupling of a large number of nephrons affect the dynamics of the collective system, and how can uncertainty, in modeling paradigms and in the parameters inherent in modeling, be incorporated into computational simulations of renal blood flow. Coupling arises in vivo, and must be included in models. Uncertainty in model parameters is a recognized consequence of our limited knowledge of the systems under study; uncertainty regarding the limitations of the very models used in our studies may alter major findings identified in the analysis. Answering these two questions will provide important steps in linking simulations with experiment. Because of the nephron's role in filtering blood, it is frequently assumed, either explicitly or implicitly, that the behavior observed in a single nephron is representative of whole kidney function. This assumption has proven valid and useful in many contexts. However, the coupling of two individual nephrons is known to induce dynamics of the pair that is not present in the individual. Massive coupling of nephrons, as it is thought to occur in the kidney, will likely elicit collective behavior from the system that cannot be guessed beforehand. Likewise, idealized modeling and specification of model parameters may not accurately reflect the environment in which the nephron exists in vivo. This project brings new mathematical ideas to the study of renal blood flow regulation, a complex biological system that plays an important role in human health.