Project Summary Abstract This research will provide information on the inner working of the kidney as it recovers from acute injury. Recovery of the kidney from acute injury is often incomplete and leaves behind a kidney that is prone to subsequent permanent decline due to physical and metabolic stresses of trying to compensate for incomplete healing. Ideally, targeted intervention would hasten recovery from acute kidney injury and diminish its long- term consequences. However, major knowledge gaps in the area of renal recovery currently preclude a rational approach to treatment. Knowledge gaps include the physical reason why the injured kidney appears to filter less fluid, the vulnerability of the injured kidney to be further injured by changes in blood pressure, or whether standard medical treatments or prescribed diets are helpful or harmful in patients recovering from kidney injury. Kidney features that are observed at the whole-kidney level emerge from events at the microscopic level and treatments have their direct effect at the microscopic level. However, there can be multiple combinations of microscopic events that could account for a given observation at the whole-kidney level. Therefore, microscopic behavior cannot be deduced from whole-kidney behavior and must be observed directly. This cannot be done in humans but can be done in rat models of human kidney injury using specialized techniques uniquely available to the investigators. Through these methods, this research will determine the effects of simple maneuvers on multiple internal variables thereby establishing boundary conditions for efficient design of future clinical trials in the field of kidney recovery.

Project Narrative Recovery from acute kidney injury (AKI) is often incomplete and leaves behind a kidney that is prone to develop chronic kidney disease (CKD). The proposed research will explore how various functions of the kidney are regulated and evolve as the kidney recovers from AKI and how the evolution and ultimate outcome are affected by pre-existing CKD, standard medical treatments including angiotensin blockade, changes in dietary NaCl, and inhibitors of the principle kidney glucose transporter, SGLT2. Experiments will employ standard rat models of AKI where key variables can be measured that cannot be measured in human subjects.