Sex and time-of-day differences in kidney oxygen consumption

Abstract

Renal hemodynamics, renal transporter expression levels, and urine excretion all exhibit circadian variations. Disturbance of these diurnal patterns is associated with hypertension and chronic kidney disease. Renal hemodynamics determines oxygen delivery, whereas renal transport and metabolism determines oxygen consumption. The balance between oxygen delivery and consumption then yields renal oxygenation. We hypothesized that kidney oxygenation also demonstrates 24-h periodicity. Another notable modulator of kidney function is sex, which has impacts on renal hemodynamics and transport function that are regulated by as well as independent of the circadian clock. The goal of this study was to investigate the diurnal and sexual variations in renal oxygen consumption and oxygenation. For this purpose, we developed computational models of rat kidney function that represent sexual dimorphism and circadian variation in renal hemodynamics and transporter activities. Model simulations predicted substantial differences in tubular Na+ transport and oxygen consumption among different nephron segments. We also simulated the effect of loop diuretics, which are used in the treatment of renal hypoxia, on the outer medullary oxygen tension. Our model predicted a significantly higher effect of loop diuretics on renal oxygenation in female rats compared to male rats. In addition, loop diuretics were more effective when administered during the active phase.