Exercise Sensitizes the Pressure Diuresis Response: Shifting Immune Landscapes May Underlie Renal Adaptations to Exercise.

Physical activity and exercise confer health benefits through actions on several physiological systems; however, the mechanisms by which they impact renal health remain poorly understood. Studies show exercise slows age-related decline in kidney function and protects against AKI. We hypothesize that exercise triggers adaptative responses, which preserve hemodynamic balance in the kidneys under stress. We evaluated running-induced adaptations in 10-14-wk-old C57BL/6J male and female mice subjected to voluntary running or in male mice subjected to forced treadmill running. We evaluated renal perfusion with contrast-enhanced ultrasound and assessed kidney function by measuring the ability to clear a volume load. Additionally, we performed flow cytometry, cytokine array, histopathology, and bulk mRNA sequencing. We found exercise significantly increased cortical microvascular blood volume (p=0.0085), as indicated by increased plateau contrast signal intensity. Additionally, exercised male, but not female, mice excreted significantly more urine in the first hour after a saline bolus (p=0.0055). At the cellular level, we observed a significant increase in kidney resident macrophages (KRMs; CD45+CD11b+F4/80hi) after treadmill training in male mice. Lastly, bulk mRNA sequencing suggested treadmill training induced changes relating to water and sodium handling as well as angiogenesis and wound healing. These data suggest that exercise alters the immune landscape of the kidney, increases renal microvascular volume, and improves sensitivity of the pressure diuresis response. Future studies will test the hypothesis that macrophages cause the functional adaptations observed.