Habitual sleep and kidney function in chronic kidney disease: the Chronic Renal Insufficiency Cohort study.

Physiological evidence suggests that sleep modulates kidney function. Our objective was to examine the cross-sectional association between kidney function and objectively-estimated habitual sleep duration, quality and timing in a cohort of patients with mild to moderate chronic kidney disease. This study involved two US clinical centers of the Chronic Renal Insufficiency Cohort (CRIC) study, including 432 participants in a CRIC ancillary sleep study. Habitual sleep duration, quality and timing were measured using wrist actigraphy for 5-7 days. Validated sleep questionnaires assessed subjective sleep quality, daytime sleepiness and risk of sleep apnea. Kidney function was assessed with the estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation, and the urinary protein to creatinine ratio. Lower estimated glomerular filtration rate was associated with shorter sleep duration (-1.1 mL min-1  1.73 m-2 per hour less sleep, P = 0.03), greater sleep fragmentation (-2.6 mL min-1  1.73 m-2 per 10% higher fragmentation, P < 0.001) and later timing of sleep (-0.9 mL min-1  1.73 m-2 per hour later, P = 0.05). Higher protein to creatinine ratio was also associated with greater sleep fragmentation (approximately 28% higher per 10% higher fragmentation, P < 0.001). Subjective sleep quality, sleepiness and persistent snoring were not associated with estimated glomerular filtration rate or protein to creatinine ratio. Thus, worse objective sleep quality was associated with lower estimated glomerular filtration rate and higher protein to creatinine ratio. Shorter sleep duration and later sleep timing were also associated with lower estimated glomerular filtration rate. Physicians treating patients with chronic kidney disease should consider inquiring about sleep and possibly sending for clinical sleep assessment. Longitudinal and interventional trials are needed to understand causal direction.

The Association of Sleep Duration and Quality with CKD Progression.

Evidence suggests that sleep disorders are common in individuals with CKD, but the influence of sleep duration and quality on CKD progression is unknown. We examined the association of habitual sleep duration and quality with CKD progression in 431 Chronic Renal Insufficiency Cohort (CRIC) Study participants, of whom 48% were women and 50% had diabetes (mean age of 60 years old, mean eGFR =38 ml/min per 1.73 m2, and median urine protein-to-creatinine ratio [UPCR] =0.20 g/g). We assessed sleep duration and quality by 5-7 days of wrist actigraphy and self-report. Primary outcomes were incident ESRD, eGFR slope, log-transformed UPCR slope, and all-cause death. Participants slept an average of 6.5 hours per night; mean sleep fragmentation was 21%. Over a median follow-up of 5 years, we observed 70 ESRD events and 48 deaths. In adjusted analyses, greater sleep fragmentation associated with increased ESRD risk (hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.07 per 1% increase in fragmentation). In adjusted mixed effects regression models, shorter sleep duration (per hour less) and greater sleep fragmentation (per 1% more) each associated with greater eGFR decline (-1.12 and -0.18 ml/min per 1.73 m2 per year, respectively; P=0.02 and P<0.01, respectively) and greater log UPCR slope (0.06/yr and 0.01/yr, respectively; P=0.02 and P<0.001, respectively). Self-reported daytime sleepiness associated with increased risk for all-cause death (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20 per one-point increase in the Epworth Sleepiness Scale score). These findings suggest that short and poor-quality sleep are unrecognized risk factors for CKD progression.

Sleep disturbances as nontraditional risk factors for development and progression of CKD: review of the evidence.

Despite the high prevalence and enormous public health implications of chronic kidney disease (CKD), the factors responsible for its development and progression are incompletely understood. To date, only a few studies have attempted to objectively characterize sleep in patients with CKD prior to kidney failure, but emerging evidence suggests a high prevalence of sleep disorders, particularly obstructive sleep apnea. Laboratory and epidemiologic studies have shown that insufficient sleep and poor sleep quality promote the development and exacerbate the severity of 3 important risk factors for CKD, namely hypertension, type 2 diabetes, and obesity. In addition, sleep disturbances might have a direct effect on CKD through chronobiological alterations in the renin-angiotensin-aldosterone system and sympathetic nervous system activation. The negative impact of sleep disorders on vascular compliance and endothelial function also may have a deleterious effect on CKD. Sleep disturbances therefore may represent a novel risk factor for the development and progression of CKD. Optimizing sleep duration and quality and treating sleep disorders may reduce the severity and delay the progression of CKD.