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.

CKD in Hispanics: Baseline characteristics from the CRIC (Chronic Renal Insufficiency Cohort) and Hispanic-CRIC Studies.

BACKGROUND: Little is known regarding chronic kidney disease (CKD) in Hispanics. We compared baseline characteristics of Hispanic participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies with non-Hispanic CRIC participants. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Participants were aged 21-74 years with CKD using age-based estimated glomerular filtration rate (eGFR) at enrollment into the CRIC/H-CRIC Studies. H-CRIC included Hispanics recruited at the University of Illinois in 2005-2008, whereas CRIC included Hispanics and non-Hispanics recruited at 7 clinical centers in 2003-2007. FACTOR: Race/ethnicity. OUTCOMES: Blood pressure, angiotensin-converting enzyme (ACE)-inhibitor/angiotensin receptor blocker (ARB) use, and CKD-associated complications. MEASUREMENTS: Demographic characteristics, laboratory data, blood pressure, and medications were assessed using standard techniques and protocols. RESULTS: Of H-CRIC/CRIC participants, 497 were Hispanic, 1,650 were non-Hispanic black, and 1,638 were non-Hispanic white. Low income and educational attainment were nearly twice as prevalent in Hispanics compared with non-Hispanics (P < 0.01). Hispanics had self-reported diabetes (67%) more frequently than non-Hispanic blacks (51%) and whites (40%; P < 0.01). Blood pressure >130/80 mm Hg was more common in Hispanics (62%) than blacks (57%) and whites (35%; P < 0.05), and abnormalities in hematologic, metabolic, and bone metabolism parameters were more prevalent in Hispanics (P < 0.05), even after stratifying by entry eGFR. Hispanics had the lowest use of ACE inhibitors/ARBs among the high-risk subgroups, including participants with diabetes, proteinuria, and blood pressure >130/80 mm Hg. Mean eGFR was lower in Hispanics (39.6 mL/min/1.73 m(2)) than in blacks (43.7 mL/min/1.73 m(2)) and whites (46.2 mL/min/1.73 m(2)), whereas median proteinuria was higher in Hispanics (protein excretion, 0.72 g/d) than in blacks (0.24 g/d) and whites (0.12 g/d; P < 0.01). LIMITATIONS: Generalizability; observed associations limited by residual bias and confounding. CONCLUSIONS: Hispanics with CKD in the CRIC/H-CRIC Studies are disproportionately burdened with lower socioeconomic status, more frequent diabetes mellitus, less ACE-inhibitor/ARB use, worse blood pressure control, and more severe CKD and associated complications than their non-Hispanic counterparts.

Self-Reported Tobacco, Alcohol, and Illicit Drug Use and Progression of Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Previous studies suggest that tobacco, alcohol, and illicit drug use is associated with CKD. We examined the associations of substance use with CKD progression and all-cause mortality among patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Chronic Renal Insufficiency Cohort Study is a prospective, longitudinal cohort study among 3939 participants with CKD in the United States. Self-reported tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug (cocaine, heroin, or methamphetamine) use were obtained at baseline and annual follow-up visits. CKD progression was defined as incident ESKD or halving of eGFR. Substance use was modeled as the cumulative average exposure to capture both recent and long-term use in multivariable time-dependent Cox regression. RESULTS: Over a median 5.5-year follow-up, 1287 participants developed CKD progression, and 1001 died. Baseline proportions of tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug use were 13%, 20%, 33%, and 12%, respectively. Compared with nonsmoking throughout follow-up, multivariable-adjusted hazard ratios for persistent tobacco smoking were 1.02 (95% confidence interval, 0.86 to 1.21) for CKD progression and 1.86 (95% confidence interval, 1.54 to 2.24) for all-cause mortality. Compared with nondrinking throughout follow-up, multivariable-adjusted hazard ratios for persistent alcohol drinking were 1.06 (95% confidence interval, 0.88 to 1.29) for CKD progression and 0.73 (95% confidence interval, 0.58 to 0.91) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent marijuana use were 0.94 (95% confidence interval, 0.82 to 1.07) for CKD progression and 1.11 (95% confidence interval, 0.96 to 1.30) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent hard illicit drug use were 1.25 (95% confidence interval, 1.00 to 1.55) for CKD progression and 1.41 (95% confidence interval, 1.10 to 1.81) for all-cause mortality. CONCLUSIONS: Hard illicit drug use is associated with higher risk of CKD progression and all-cause mortality, tobacco smoking is associated with higher risk of all-cause mortality, and alcohol drinking is associated with lower risk of all-cause mortality among patients with CKD.

Self-reported Medication Adherence and CKD Progression.

INTRODUCTION: In the general population, medication nonadherence contributes to poorer outcomes. However, little is known about medication adherence among adults with chronic kidney disease (CKD). We evaluated the association of self-reported medication adherence with CKD progression and all-cause death in patients with CKD. METHODS: In this prospective observational study of 3305 adults with mild-to-moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, the baseline self-reported medication adherence was assessed by responses to 3 questions and categorized as high, medium, and low. CKD progression (50% decline in eGFR or incident end-stage renal disease) and all-cause death were measured using multivariable Cox proportional hazards. RESULTS: Of the patients, 68% were categorized as high adherence, 17% medium adherence, and 15% low adherence. Over a median follow-up of 6 years, there were 969 CKD progression events and 675 deaths. Compared with the high-adherence group, the low-adherence group experienced increased risk for CKD progression (hazard ratio = 1.27, 95% confidence interval = 1.05, 1.54) after adjustment for sociodemographic and clinical factors, cardiovascular medications, number of medication types, and depressive symptoms. A similar association existed between low adherence and all-cause death, but did not reach standard statistical significance (hazard ratio = 1.14 95% confidence interval = 0.88, 1.47). CONCLUSION: Baseline self-reported low medication adherence was associated with an increased risk for CKD progression. Future work is needed to better understand the mechanisms underlying this association and to develop interventions to improve adherence.

Vascular risk factors and cognitive impairment in chronic kidney disease: the Chronic Renal Insufficiency Cohort (CRIC) study.

BACKGROUND AND OBJECTIVES: Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score>1 SD below the mean score. RESULTS: Among 3591 participants, the mean age was 58.2±11.0 years, and the mean estimated GFR (eGFR) was 43.4±13.5 ml/min per 1.73 m2. Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR<30 ml/min per 1.73 m2 was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m2. This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders. CONCLUSIONS: The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

Chronic Renal Insufficiency Cohort (CRIC) Study: baseline characteristics and associations with kidney function.

BACKGROUND AND OBJECTIVES: The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with CKD. We examined baseline demographic and clinical characteristics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seven clinical centers recruited adults who were aged 21 to 74 yr and had CKD using age-based estimated GFR (eGFR) inclusion criteria. At baseline, blood and urine specimens were collected and information regarding health behaviors, diet, quality of life, and functional status was obtained. GFR was measured using radiolabeled iothalamate in one third of participants. RESULTS: A total of 3612 participants were enrolled with mean age +/- SD of 58.2 +/- 11.0 yr; 46% were women, and 47% had diabetes. Overall, 45% were non-Hispanic white, 46% were non-Hispanic black, and 5% were Hispanic. Eighty-six percent reported hypertension, 22% coronary disease, and 10% heart failure. Mean body mass index was 32.1 +/- 7.9 kg/m(2), and 47% had a BP >130/80 mmHg. Mean eGFR was 43.4 +/- 13.5 ml/min per 1.73 m(2), and median (interquartile range) protein excretion was 0.17 g/24 h (0.07 to 0.81 g/24 h). Lower eGFR was associated with older age, lower socioeconomic and educational level, cigarette smoking, self-reported CVD, peripheral arterial disease, and elevated BP. CONCLUSIONS: Lower level of eGFR was associated with a greater burden of CVD as well as lower socioeconomic and educational status. Long-term follow-up of participants will provide critical insights into the epidemiology of CKD and its relationship to adverse outcomes.