Devreotes Prize for Early-stage Investigator Impact: Functional coupling of metabolic oscillations and hemodynamics in the kidney

Age-related decline of renal function is faster in males than in age-matched females, manifesting in increased susceptibility to both chronic and acute kidney diseases among males, in humans and rodents. Glomerular filtration rate (GFR) is tightly regulated by tubuloglomerular feedback (TGF) within renal tubules to optimize filtration of plasma and reabsorption of essential molecules, which is highly energy demanding. Intravital microscopy were used to capture in vivo GFR oscillations and spontaneous metabolic oscillations in individual renal tubular epithelial cells, revealing functional coupling between cell-level metabolism and tissue-level fluid flow, as well as intriguing sex-biased characteristics. Mathematical modeling of TGF suggests that dynamic features of the system differ between male and female kidneys due to differential metabolic regulation in renal tubules, resulting in male kidneys being more prone to stress-induced damage, therefore providing an explanation for sexual dimorphism in renal aging and diseases. With this mechanistic model, this work also provides insight into how pharmacological interventions can be employed to confer renoprotection.