The Kidney Clock Contributes to Timekeeping by the Master Circadian Clock

Area of Science:

• Chronobiology
• Nephrology
• Sleep Medicine

Background:

• The kidney possesses a robust internal circadian clock.
• Kidney failure is associated with disrupted sleep patterns.
• The precise mechanisms linking kidney dysfunction to circadian disruption are unclear.

Purpose of the Study:

• To investigate if aberrant kidney circadian rhythms contribute to sleep disturbances in chronic kidney disease (CKD).
• To examine the impact of CKD on the kidney's circadian clock function in vivo and in vitro.
• To explore the kidney's role in whole-body circadian timekeeping.

Main Methods:

• Adenine-induced chronic kidney disease (CKD) model in mice.
• Assessment of behavioral circadian rhythms.
• In vitro analysis of kidney and suprachiasmatic nucleus (SCN) clock pacing.
• Comparison with choroid plexus clock function.

Main Results:

• CKD mice exhibited unstable behavioral circadian rhythms.
• The master clock (SCN) pacing remained intact in isolated conditions.
• The kidney clock showed reduced robustness and a prolonged period under CKD.
• Kidney clock dysfunction in CKD is analogous to choroid plexus clock disruption.

Conclusions:

• Aberrant kidney circadian rhythms are implicated in sleep disturbances associated with CKD.
• The kidney functions as a significant peripheral clock influencing whole-body circadian timing.
• Disruption of the kidney clock may impact the central circadian pacemaker, affecting sleep-wake cycles.