Importance Coronary artery calcification (CAC) is highly prevalent in patients with pre-dialysis chronic kidney disease (CKD). However, there are sparse data on the association of CAC with subsequent risk of cardiovascular disease (CVD) and all-cause mortality in this population. Objectives To study the prospective association of CAC with risk of CVD and all-cause mortality among patients with pre-dialysis CKD. Design, Setting, and Participants Chronic Renal Insufficiency Cohort study recruited adults aged 21–74 years with an estimated-glomerular filtration rate (eGFR) of 20–70 mL/min/1.73 m2 from seven clinical centers in the US. Of them, 1,541 participants without CVD at baseline who had CAC measures were included in current analyses. Exposure CAC was assessed by electron-beam computed tomography or multi-detector computed tomography. Main Outcomes and Measures Incidence of CVD (including myocardial infarction, heart failure, and stroke) and all-cause mortality were reported every six months and confirmed by medical record adjudication. Results During an average of 5.9 years of follow-up, we observed 188 CVD (60 myocardial infarction, 120 heart failure, and 27 stroke) and 137 deaths. In Cox proportional hazards models adjusted for age, gender, race, clinical site, education, physical activity, total cholesterol, HDL-cholesterol, systolic blood pressure, antihypertensive treatment, current cigarette smoking, diabetes, body-mass index, C-reactive protein, hemoglobin A1c, phosphate, troponin T, log-N-terminal pro-B-type natriuretic peptide, fibroblast growth factor-23, eGFR, and proteinuria, the hazard ratios (95% confidence interval [CI]) associated with one standard deviation of CAC were 1.40 (1.16 to 1.69, p<.001) for CVD, 1.44 (1.02 to 2.02, p=.04) for myocardial infarction, 1.39 (1.10 to 1.76, p=.006) for heart failure, and 1.19 (0.94 to 1.51, p=.15) for all-cause mortality. In addition, inclusion of CAC score led to significant increase in c-statistic 0.02 (95% CI 0.00 to 0.09, p<.001) for predicting CVD over all above-mentioned established and novel CVD risk factors. Conclusion and Relevance CAC is independently and significantly related to the risks of CVD, myocardial infarction, and heart failure in CKD patients. In addition, CAC improves risk prediction for CVD, myocardial infarction, and heart failure over established and novel CVD risk factors among CKD patients, although the change in c-statistics is small.

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.

Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease (CKD), prior to starting hemodialysis. We determined the association between SBP and mortality at advanced CKD and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort (CRIC) participants with advanced CKD followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants: 1) had an estimated glomerular filtration rate <30 ml/min/1.73m2 (N=1,705); 2) initiated hemodialysis and had dialysis-unit SBP measures (N=403) and; 3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a CRIC study visit (N=326). Cox models adjusted for demographics, cardiovascular risk factors and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced CKD, there was no association between SBP and mortality (HR 1.02 [95% CI: 0.98–1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (HR 1.26 [95% CI: 1.14–1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP which may merit more consideration as a target for clinical management and in interventional trials.

Novel biomarkers may improve our ability to predict which patients with chronic kidney disease (CKD) are at higher risk for progressive loss of renal function. Here we assessed the performance of urine neutrophil gelatinase-associated lipocalin (NGAL) for outcome prediction in a diverse cohort of 3386 patients with CKD in the CRIC study. In this cohort, the baseline mean estimated glomerular filtration rate (eGFR) was 42.4 ml/min/1.73m2; the median 24-hour urine protein was 0.2 gm/day; and the median urine NGAL concentration was 17.2 ng/mL. Over an average follow-up of 3.2 years, there were 689 cases in which the eGFR was decreased by half or incident end-stage renal disease developed. Even after accounting for eGFR, proteinuria and other known CKD progression risk factors, urine NGAL remained a significant independent risk factor (Cox model hazard ratio 1.70 highest to lowest quartile). The association between baseline urine NGAL levels and risk of CKD progression was strongest in the first two years of biomarker measurement. Within this time frame, adding urine NGAL to a model which included eGFR, proteinuria and other CKD progression risk factors led to net reclassification improvement of 24.7%; but the C-statistic remained nearly identical. Thus, while urine NGAL was an independent risk factor of progression among patients with established CKD of diverse etiology, it did not substantially improve prediction of outcome events.

Background: Low health literacy in the general population is associated with increased risk of death and hospitalization. The evaluation of health literacy in individuals with predialysis chronic kidney disease (CKD) is limited. Methods: We conducted a cross-sectional study to evaluate the associations of limited health literacy with kidney function and cardiovascular disease (CVD) risk factors in 2,340 non-Hispanic (NH) Whites and Blacks aged 21 – 74 years with mild-to-moderate CKD. Limited health literacy was defined as a Short Test of Functional Health Literacy in Adults (STOFHLA) score ≤ 22. Outcomes evaluated included estimated glomerular filtration rate (eGFR), 24-hour urine protein excretion, and CVD risk factors. Results: The prevalence of limited health literacy was 28% in NH-Blacks and 5% in NH-Whites. Compared with participants with adequate health literacy, those with limited health literacy were more likely to have lower eGFR (34 vs. 42 mL/min/1.73 m2); higher urine protein/24-hours (0.31 vs. 0.15 g); and higher self-reported CVD (61 vs. 37%); and were less likely to have BP < 130/80 mmHg (51 vs. 58%); p ≤ 0.01 for each comparison. After adjustment, limited health literacy was associated with self-reported CVD (OR 1.51, 95% CI 1.13 – 2.03) and lower eGFR (β –2.47, p = 0.03). Conclusion: In this CKD cohort, limited health literacy was highly prevalent, especially among NH-Blacks, and it was associated with lower eGFR and a less favorable CVD risk factor profile. Further studies are needed to better understand these associations and inform the development of health literacy interventions among individuals with CKD.