Circadian rhythms in glomerular filtration govern natriuresis and diuretic responsiveness

Jun 18, 2026Frontiers in physiology

Daily body clock controls kidney filtering, salt removal, and response to water pills

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Abstract

Key Natransporters exhibit circadian rhythms that influence renal function and diuretic responses.

Circadian regulation affects the abundance and activity of renal transporter proteins involved in sodium transport.
Conditional knockdown of the Bmal1 gene results in decreased oscillations of transporter activity and altered sodium excretion patterns.
In hypertensive conditions, sodium transport shifts from proximal to distal segments, enhancing overall sodium and water excretion.
Daily patterns of sodium excretion are primarily influenced by variations in single-nephron glomerular filtration rate.
Optimal timing for diuretic use may vary based on individual circadian patterns rather than a fixed schedule.

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Kidney function exhibits circadian rhythms that arise in part from clock-gene-mediated regulation of renal transporter proteins. Key Natransporters under circadian control include NHE3, SGLT1, NKCC2, NCC, and ENaC, which are targeted by commonly prescribed diuretics. The present study uses computational models of nephron transport to investigate how circadian regulation influences renal function and the natriuretic responses to diuretics in normotensive and Ang II-induced hypertensive rat kidneys. Simulations of conditional Bmal1 knockdown predict marked attenuation of transporter oscillations, segment-specific changes in mean transporter abundance, and a loss of the normal dipping pattern in Naexcretion. In the hypertensive kidney, Natransport is redistributed from proximal to distal segments, increasing overall natriuresis and diuresis while largely preserving the phase of excretory rhythms when filtration retains its circadian oscillation. Across normotensive and hypertensive conditions, the model predicts that the phase and amplitude of daily excretory rhythms are primarily determined by oscillations in single-nephron glomerular filtration rate (SNGFR). When SNGFR exhibits a normal circadian rhythm ("dippers"), diuretic-induced natriuresis is greatest during the active phase. In contrast, when SNGFR rhythms are absent ("non-dippers"), the time of maximal natriuretic response shifts to the inactive phase, when transporter expression is lowest. Thus, the optimal time of diuretic administration depends on circadian phenotype rather than clock time alone. These findings highlight the importance of renal circadian regulation in determining diuretic responsiveness and suggest that dosing strategies may need to account for individual dipping status. + + +

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Circadian rhythms in glomerular filtration govern natriuresis and diuretic responsiveness

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