Weekly issue 2026-W41 ·
Pkd1 Deficiency Causes Intrinsic Renal Circadian Clock Dysfunction
Plain language
The body runs on an internal 24-hour clock, and organs such as the kidney have their own clocks too. In mice with PKD, the daily rhythm of drinking and passing urine became more disrupted as cysts grew. In cystic kidneys, the clock genes swung less and fell out of step, and losing the PKD1 gene also weakened the clock in kidney cells grown in the lab. This suggests PKD1 matters for the kidney's own clock, although the authors say more work is needed to separate direct effects from changes caused by the cysts. This is animal and cell research.
Clinical note
Preclinical study at organism, organ and cell level. Slowly progressive Pkd1RC/RC mice showed progressive disruption of diurnal water intake and urine output rhythms, paralleling cystic burden. Cystic kidneys had dampened, desynchronised core clock gene oscillations and PER2::LUC bioluminescence in explants, more pronounced in rapidly progressive Pkd1-KO mice. Pkd1 loss blunted clock gene oscillations in synchronised proximal tubular and inner medullary collecting duct cells in vitro, indicating cell-autonomous dysfunction independent of systemic cues. Builds on the group's earlier finding that renal clock disruption accelerates cyst growth. Direct effects of Pkd1 loss versus secondary cystic remodelling in vivo remain to be separated.
Question for your next visit
Does my daily routine, such as sleep or when I drink fluids, matter for my kidneys?