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Circadian disruption (CD) is a risk factor in cardiovascular disease although we know little about its effects on the kidney.

Previous work from our group showed that short-term CD in mice by
restricting food availability to the daytime is sufficient to invert diurnal blood pressure rhythms
yet kidney excretory function remained aligned with the light-dark cycle. Thus, we hypothesize
that long-term CD will result in kidney damage. C57BL/6 mice on a regular 12:12 light:dark cycle
were placed on an inactive time-restricted feeding (iTRF, 12h food access during the day/lights
on) or ad libitum feeding protocol for 8 weeks. Both sexes had an inversion in diurnal water
intake rhythms but maintained normal diurnal urinary excretion. Aldosterone (aldo) and
endothelin-1 (ET-1) contribute to circadian timing of sodium transport systems in the collecting
duct. While male iTRF mice maintained their diurnal rhythm of aldosterone excretion
(2.0±1.4ng/hr in light, p=0.06; 7.8±3.1ng/hr in dark, p=0.37, n=6), female iTRF mice lost their
diurnal rhythm (4.4±2.7ng/hr in light, p=0.85; 4.4±3.1ng/hr in dark, p=0.11, n=6). Male mice
with iTRF had significantly lower ET-1 excretion, but maintained the diurnal variation. In
contrast, female iTRF mice demonstrated an inverted ET-1 excretion pattern (18.5±6.3ng/hr in
light vs. 7.3±2.9ng/hr in dark, p=0.03, n=3) compared to ad lib fed mice (18.9±2.1ng/hr in light
vs. 33.7±5.6ng/hr in dark, p=0.01, n=3). Picrosirus red staining of kidneys revealed a striking
increase in glomerular and interstitial fibrosis in iTRF male mice as compared to their ad lib
counterparts. In contrast, iTRF female mice appeared to be completely protected from
increased fibrosis. These results support our hypothesis that long-term CD due to timing of food
intake exacerbates kidney damage. However, females were protected against renal fibrosis,
perhaps due in part to an ability to better modulate kidney rhythms in response to food timing.

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