The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; =1330) or<140 mm Hg (standard group; =1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD ( values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m per year; <0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

Depression is highly prevalent and is associated with poor quality of life and increased mortality among adults with chronic kidney disease (CKD), including those with end-stage renal disease (ESRD). However, there are several important differences in the diagnosis, epidemiology, and management of depression between patients with non−dialysis-dependent CKD and ESRD. Understanding these differences may lead to a better understanding of depression in these 2 distinct populations. First, diagnosing depression using self-reported questionnaires may be less accurate in patients with ESRD compared with CKD. Second, although the prevalence of interview-based depression is approximately 20% in both groups, the risk factors for depression may vary. Third, potential mechanisms of depression might also differ in CKD versus ESRD. Finally, considerations regarding the type and dose of antidepressant medications vary between CKD and ESRD. Future studies should further examine the mechanisms of depression in both groups, and test interventions to prevent and treat depression in these populations.

SummaryBackground and objectives Levels of fibroblast growth factor 23 (FGF23) and inflammatory markers are commonly elevated in CKD, and each is associated with adverse clinical outcomes. This study tested the hypothesis that FGF23 is independently associated with inflammation in CKD.Design, setting, participants, & measurements The association between levels of FGF23 and the inflammatory markers IL-6, C-reactive protein (CRP), TNF-a, and fibrinogen was assessed in a cross-sectional analysis of 3879 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study between June 2003 and September 2008.Results FGF23 correlated directly with IL-6 (r=0.4), CRP (r=0.2), TNF-a (r=0.4), and fibrinogen (r=0.3; P,0.001 for each). In univariate and multivariable-adjusted linear regression analyses, natural log (ln) transformed FGF23 was significantly associated with lnIL-6, lnCRP, lnTNF-a, and fibrinogen (P,0.001 for each). Each unit higher lnFGF23 was associated with severe inflammation, defined as levels of all inflammatory markers in the highest 25th percentile, in univariate (odds ratio [OR], 2.4 [95% confidence interval (CI), 2.0-2.9]) and multivariable-adjusted (OR, 2.0 [95% CI, 1.6-2.5]) logistic regression analyses. Ascending FGF23 quartiles were independently associated with severe inflammation (OR, 5.6 for the highest versus lowest FGF23 quartile [95% CI, 2.3-13.9]; P for trend , 0.001).Conclusions Higher FGF23 levels are independently associated with higher levels of inflammatory markers in patients with CKD and with significantly greater odds of severe inflammation. Future studies should evaluate whether inflammation modifies the association between FGF23 and adverse outcomes in CKD.

Background In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD). Study Design Prospective cohort. Setting & Participants 3006 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictors Four lifestyle factors (regular physical activity, body mass index [BMI] 20–<25 kg/m2, nonsmoking, and “healthy diet”), individually and in combination. Outcomes CKD progression (50% decrease in estimated glomerular filtration rate or end-stage renal disease), atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease), and all-cause mortality. Measurements Multivariable-adjusted Cox proportional hazards. Results During median follow-up of 4 years, we observed 726 CKD progression events, 353 atherosclerotic events, and 437 deaths. BMI ≥ 25 kg/m2 and nonsmoking were associated with reduced risk of CKD progression (HRs of 0.75 [95% CI, 0.58–0.97] and 0.61 [95% CI, 0.45–0.82] for BMIs of 25–<30 and ≥30, respectively, vs. 20–<25 kg/m2; HR for nonsmoking of 0.68 [95% CI, 0.55–0.84] compared to current smoker reference group) and reduced risk of atherosclerotic events (HRs of 0.67 [95% CI, 0.46–0.96] for BMI 25–<30 vs. 20–<25 kg/m2 and 0.55 [95% CI, 0.40–0.75] vs. current smoker). Factors associated with reduced all-cause mortality were regular physical activity (HR, 0.64 [95% CI, 0.52–0.79] vs. inactive), BMI ≥30 kg/m2 (HR, 0.64 [95% CI, 0.43–0.96] vs. 20–<25 kg/m2) and nonsmoking (HR, 0.45 [95% CI, 0.34–0.60] vs. current smoker). BMI <20 kg/m2 was associated with increased all-cause mortality risk (HR, 2.11 [95% CI, 1.13–3.93] vs. 20–25 kg/m2). Adherence to all four lifestyle factors was associated with 68% lower risk of all-cause mortality compared to adherence to no lifestyle factors (HR, 0.32; 95% CI, 0.11–0.89). Limitations Lifestyle factors were only measured once. Conclusions Regular physical activity, nonsmoking, and BMI ≥25 kg/m2 were associated with lower risk of adverse outcomes in this cohort of individuals with CKD.

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Background In the United States, incidence of ESRD is 1.5 times higher in men than in women, despite men's lower prevalence of CKD. Prior studies, limited by inclusion of small percentages of minorities and other factors, suggested that men have more rapid CKD progression, but this finding has been inconsistent.Methods In our prospective investigation of sex differences in CKD progression, we used data from 3939 adults (1778 women and 2161 men) enrolled in the Chronic Renal Insufficiency Cohort Study, a large, diverse CKD cohort. We evaluated associations between sex (women versus men) and outcomes, specifically incident ESRD (defined as undergoing dialysis or a kidney transplant), 50% eGFR decline from baseline, incident CKD stage 5 (eGFR,15 ml/min per 1.73 m 2 ), eGFR slope, and all-cause death.Results Participants' mean age was 58 years at study entry; 42% were non-Hispanic black, and 13% were Hispanic. During median follow-up of 6.9 years, 844 individuals developed ESRD, and 853 died. In multivariable regression models, compared with men, women had significantly lower risk of ESRD, 50% eGFR decline, progression to CKD stage 5, and death. The mean unadjusted eGFR slope was 21.09 ml/min per 1.73 m 2 per year in women and 21.43 ml/min per 1.73 m 2 per year in men, but this difference was not significant after multivariable adjustment.Conclusions In this CKD cohort, women had lower risk of CKD progression and death compared with men. Additional investigation is needed to identify biologic and psychosocial factors underlying these sexrelated differences.Although women in the United States have a greater prevalence of CKD compared with men, men are 1.5 times more likely to develop ESRD. The reasons for this sex-related disparity are not well understood. In their prospective cohort study evaluating sex-related differences in CKD progression, the authors evaluated data from 3939 adults enrolled in the Chronic Renal Insufficiency Cohort Study, a large and diverse CKD cohort. They find a lower risk of ESRD and death from any cause in women compared with men, and these differences remained statistically significant, even after adjustment for sociodemographic characteristics, baseline kidney function, cardiovascular risk factors, medications, and markers of bone mineral metabolism. Additional research is needed to elucidate biologic and psychosocial factors underlying the sex-related difference in CKD progression.

Despite the high prevalence and enormous public health implications of chronic kidney disease (CKD), the factors responsible for its development and progression remain incompletely understood. To date, only a few studies have attempted to objectively characterize sleep in CKD patients 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 three 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 may also have also have a deleterious effect on CKD. Sleep disturbances may therefore 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.

Background and objectives Low health-related quality of life is associated with increased mortality in patients with ESRD. However, little is known about demographic and clinical factors associated with health-related quality of life or its effect on outcomes in adults with CKD.Design, settings, participants, & measurements Data from 3837 adult participants with mild to severe CKD enrolled in the prospective observational Chronic Renal Insufficiency Cohort and Hispanic Chronic Renal Insufficiency Cohort Studies were analyzed. Health-related quality of life was assessed at baseline with the Kidney Disease Quality of Life-36 and its five subscales: mental component summary, physical component summary, burden of kidney disease (burden), effects of kidney disease (effects), and symptoms and problems of kidney disease (symptoms). Low health-related quality of life was defined as baseline score .1 SD below the mean. Using Cox proportional hazards analysis, the relationships between low health-related quality of life and the following outcomes were examined: (1) CKD progression (50% eGFR loss or incident ESRD), (2) incident cardiovascular events, and (3) all-cause death.Results Younger age, women, low education, diabetes, vascular disease, congestive heart failure, obesity, and lower eGFR were associated with low baseline health-related quality of life (P,0.05). During a median follow-up of 6.2 years, there were 1055 CKD progression events, 841 cardiovascular events, and 694 deaths. Significantly higher crude rates of CKD progression, incident cardiovascular events, and all-cause death were observed among participants with low health-related quality of life in all subscales (P,0.05). In fully adjusted models, low physical component summary, effects, and symptoms subscales were independently associated with a higher risk of incident cardiovascular events and death, whereas low mental component summary was independently associated with a higher risk of death (P,0.05). Low health-related quality of life was not associated with CKD progression.Conclusions Low health-related quality of life across several subscales was independently associated with a higher risk of incident cardiovascular events and death but not associated with CKD progression.