Rest-activity Circadian Rhythms Are Disrupted In Patients With Chronic Kidney Diseases

Circadian rhythms of activity are emerging as important contributors to health, however, activity rhythms in patients with chronic kidney disease (CKD) have not yet been defined. PURPOSE: The purpose of this study was to characterize the rest activity rhythms (RAR) in CKD patients and to examine their association with all-cause mortality. METHODS: The National Health and Nutrition Examination Survey 2011-2014 was analyzed. Patients with Stages 3-5 CKD (n = 1114; Mean age: 47.4 years, 48% female) were compared with non-CKD individuals (n = 5885, Mean age: 59.2 years old, 48% female). Pre-processed wrist-worn accelerometer data were obtained as a form of monitor-independent movement summary (MIMS) unit. After screening minute-by-minute MMIS for non-wear and missing data, the imputed data were averaged into 10-minute intervals and processed for RAR analyses. First, activity regularity (inter-daily stability (IS)) and activity fragmentation (intra-daily variability (IV)) were calculated. Second, a parametric cosinor model was fitted to each individual with a varying number of cosinor components from which the rhythmic strength (amplitude), the rhythm adjusted mean (mesor), and the timing of peak activity (acrophase) were calculated. Lastly, Cox regression was performed to compare RAR indicators for the prediction of all-cause mortality, which was linked to the mortality follow-up through December 31, 2019. RESULTS: The RAR of the majority of adults was best explained by a multi-component cosinor model, with the 4-component model fitting the largest proportion of the sample (67%) for both CKD and non-CKD groups. CKD patients had a lower rhythmic amplitude and mesor (Ps < .001). Patients with CKD also exhibited greater fragmentation in RAR compared to non-CKD adults (mean IV [95% CI], 0.73 [0.71,0.76] vs. 0.68 [0.66,0.69]; P < .001). Among CKD patients, rhythmic amplitude (Hazard ratio (HR) = 0.87), mesor (HR = 0.87), and activity fragmentation (HR = 1.97) were significantly associated with an increased risk of all-cause mortality. CONCLUSIONS: Patients with CKD showed a dampened rhythmic amplitudes and greater fragmentation of activity rhythms that were associated with a higher risk of all-cause mortality. These data suggest that circadian behavior rhythms may be important biomarkers for health in CKD.