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This Viewpoint questions whether the use of race as a variable in the CKD-EPI equation to estimate glomerular filtration rate (eGFR) puts some black patients at a disadvantage with respect to renally cleared antibiotics and access to kidney transplantation, and argues that more objective clinical variables might improve the equation’s precision while avoiding problems with identifying race.

An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44615 ml/min per 1.73 m 2 ). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR] . Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.

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.

CKD is a major risk factor for ESRD, cardiovascular disease, and premature death. Whether dietary sodium and potassium intake affect CKD progression remains unclear. We prospectively studied the association of urinary sodium and potassium excretion with CKD progression and all-cause mortality among 3939 patients with CKD in the Chronic Renal Insufficiency Cohort Study. Urinary sodium and potassium excretion were measured using three 24-hour urine specimens, and CKD progression was defined as incident ESRD or halving of eGFR. During follow-up, 939 CKD progression events and 540 deaths occurred. Compared with the lowest quartile of urinary sodium excretion (,116.8 mmol/24 h), hazard ratios (95% confidence intervals) for the highest quartile of urinary sodium excretion ($194.6 mmol/24 h) were 1.54 (1.23 to 1.92) for CKD progression, 1.45 (1.08 to 1.95) for all-cause mortality, and 1.43 (1.18 to 1.73) for the composite outcome of CKD progression and all-cause mortality after adjusting for multiple covariates, including baseline eGFR. Additionally, compared with the lowest quartile of urinary potassium excretion (,39.4 mmol/24 h), hazard ratios for the highest quartile of urinary potassium excretion ($67.1 mmol/24 h) were 1.59 (1.25 to 2.03) for CKD progression, 0.98 (0.71 to 1.35) for all-cause mortality, and 1.42 (1.15 to 1.74) for the composite outcome. These data indicate that high urinary sodium and potassium excretion are associated with increased risk of CKD progression. Clinical trials are warranted to test the effect of sodium and potassium reduction on CKD progression.

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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.

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.