Lower circadian rhythmicity of rest-activity patterns is associated with a higher risk of chronic kidney disease in older adults

As the global burden of chronic kidney disease (CKD) continues to rise, it is important to identify factors that may support preservation of kidney function with age. Circadian rhythmicity declines with age, and evidence suggests that circadian rhythms influence renal physiology, yet their role in long-term kidney health remains underexplored. We tested the hypothesis that lower circadian rhythmicity would be associated with an elevated risk of kidney function decline. About 1315 older adults participating in the Rush Memory and Aging Project, a prospective community-based cohort study of the chronic conditions of aging, were studied. The median age of participants was 81.5 years [IQR: 71.8-91.2], 76.3% were female, and 93.7% identified as Caucasian. The stability of the circadian activity rhythm was quantified from up to 10 consecutive days of wrist activity using interdaily stability (IS) metric. Lower baseline IS was associated with lower eGFR (estimate = -1.9 ml/min/1.73 m² per 1SD lower IS, SE 0.4, <i>p</i> = 5.0 × 10^-6). Among those without baseline CKD (eGFR < 60 ml/min/1.73 m²), lower IS was associated with a ~ 25% higher future risk of developing CKD (HR 1.26, 95% CI 1.11-1.43) over a 5-years period, approaching the increased hazard associated with diabetes (HR 1.37). Effects were independent of known CKD risk factors including age, sex, obesity, hypertension, and diabetes, as well as multiple measures of sleep quality. Reduced circadian rhythmicity may therefore represent a novel modifiable risk factor for age-related decline in kidney function and CKD.