Adam T. Whaley-Connell, MD, James R. Sowers, MD, Joseph A. Vassalotti, MD, Moro O. Salifu, MD, MPH, Suying Li, PhD,

Transcription

1 Prevalence and Associations of of CKD: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) Samy I. McFarlane, MD, MPH, Shu-Cheng Chen, MS, 2 3 Adam T. Whaley-Connell, MD, 3 4,5 1 James R. Sowers, MD, Joseph A. Vassalotti, MD, Moro O. Salifu, MD, MPH, Suying Li, PhD, 2 Changchun Wang, MS, 2 George Bakris, MD, Peter A. McCullough, MD, MPH, Allan J. Collins, MD, 8,9 and Keith C. Norris, MD, on behalf of the Kidney Early Evaluation Program Investigators Background: Early identification of anemia of chronic kidney disease may be important for the development of preventive strategies. We compared anemia prevalence and characteristics in the National Kidney Foundation Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) populations. Methods: Clinical, demographic, and laboratory data were collected from August 2000 to December 31, 2006, from participants in KEEP, a community-based health-screening program targeting individuals 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. was defined as hemoglobin level less than 13.5 g/dl for men and less than 12.0 g/dl for women (Kidney Disease Outcomes Quality Initiative [KDOQI] 2006) or less than 13.0 g/dl for men and less than 12.0 g/dl for women (World Health Organization [WHO]). Results: In KEEP (n 70,069), 68.3% of participants, and in NHANES (n 17,061), 52% of participants, were women. African Americans represented 33.9% of the KEEP and 11.2% of the NHANES cohorts, and Hispanics comprised 12.4% of KEEP and 13.2% of NHANES. Using the KDOQI classification, anemia was present in 13.9% and 6.3% of KEEP and NHANES participants, whereas using the WHO classification, anemia was present in 11.8% and 5.3%, respectively. In adjusted analysis of KEEP data, KDOQI-defined anemia was significantly more likely in men (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.23 to 1.37); this pattern was reversed when using WHO-defined anemia (OR, 0.68; 95% CI, 0.64 to 0.72). Adjusted odds of anemia were greater for African American than white KEEP participants (OR, 2.98; 95% CI, 2.80 to 3.16; OR, 3.00; 95% CI, 2.81 to 3.20 for KDOQI- and WHO-defined anemia, respectively). Conclusion: was twice as common in the targeted KEEP chronic kidney disease screening program cohort than in the NHANES sample population. African Americans had a 3-fold increased likelihood of anemia compared with whites. Targeted screening can identify anemia in a high-risk population. Am J Kidney Dis 51(S2):S46-S by the National Kidney Foundation, Inc. INDEX WORDS: ; chronic kidney disease; diabetes; race; sex. hronic kidney disease (CKD) is highly C prevalent in the US population, with recent estimates indicating that up to 16.5% of 1 people aged 20 years or older have the disease. African Americans and other racial and ethnic 2,3 minority groups are at increased risk of CKD. is a common complication of CKD and is associated with increased risk of cardiovascular disease (CVD), morbidity, and mortality, par- 4,5 ticularly in high-risk populations. CVD risk in patients with CKD involves traditional and nontraditional risk factors. 4-9 Traditional risk factors From the 1 Division of Endocrinology, SUNY-Downstate and Kings County Hospital Centers, Brooklyn, NY; 2 Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, MN; 3 University of Missouri-Columbia School of Medicine, Columbia, MO; 4 National Kidney Foundation; 5 Department of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, NY; 6 Hypertensive Diseases Unit, Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Pritzker School of Medicine, Chicago, IL; 7 Department of Medicine, Divisions of Cardiology, Nutrition and Preventive Medicine, William Beaumont Hospital, Royal Oak, MI; 8 Charles R. Drew University of Medicine and Science; and 9 David Geffen School of Medicine, University of California, Los Angeles, CA. Received November 21, Accepted in revised form December 28, A list of the members of the Kidney Early Evaluation Program Investigators appears at the end of this article. Address correspondence to Samy I. McFarlane, MD, MPH, Department of Medicine, Box 50, State University of New York, Health Science Center at Brooklyn, Kings County Hospital Center, 450 Clarkson Ave, Brooklyn, NY smcfarlane@downstate.edu 2008 by the National Kidney Foundation, Inc /08/ $34.00/0 doi: /j.ajkd S46 American Journal of Kidney Diseases, Vol 51, No 4, Suppl 2 (April), 2008: pp S46-S55

2 in CKD Data From KEEP and NHANES Population S47 include diabetes, hypertension, obesity, dyslipidemia, smoking, and advanced age. 8 Nontraditional risk factors include hyperhomocysteinemia, hyperparathyroidism, hyperphosphatemia, endothelial dysfunction, diastolic dysfunction, and anemia, which is increasingly recognized in this patient population. 6,7,9 of CKD generally is attributed to absolute or relative erythropoietin deficiency. However, other factors, such as iron deficiency, blood loss, shortened red blood cell life span, and inflammation, may contribute to its development. 10,11 In the general population, anemia is more prevalent and severe in African Americans than whites. 12,13 Although racial and ethnic differences in anemia prevalence and severity were noted in patients with CKD, 14 the extent and characteristics of anemia in populations at risk of CKD are less well defined. Early identification of anemia, particularly in high-risk populations, could lead to effective preventive and therapeutic strategies to improve outcomes. Thus, better understanding of the characteristics of this population has potential public health benefits. We examined the prevalence and associations of anemia in participants in the Kidney Early Evaluation Program (KEEP), a large free communitybased CKD screening program, and compared them with the National Health and Nutrition Examination Survey (NHANES) , a representative sample of the US general population. KEEP targets high-risk populations; eligible participants are 18 years or older and have a personal or family history of diabetes or hypertension or a family history of kidney disease. Conversely, NHANES surveys were targeted toward randomized cohorts that are generalizable to the US population. The objectives of this study are to: (1) assess the prevalence of anemia in the KEEP and NHANES populations by risk groups, including age, sex, race, diabetes, and CVD, by using National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) and World Health Organization (WHO) anemia definitions; (2) assess the prevalence of CKD stages in anemic patients across the different risk groups in the KEEP and NHANES cohorts; and (3) identify factors associated with significant odds of anemia in the CKD high-risk population of the KEEP program. METHODS Definitions KEEP and the NHANES database are fully described elsewhere in this supplement. 15 Disease definitions are as follows. History of diabetes is defined as self-reported diabetes or retinopathy, and history of hypertension, as selfreported hypertension. is defined as hemoglobin level less than 13.5 g/dl ( 135 g/l) for men and less than 12.0 g/dl ( 120 g/l) for women (KDOQI 2006) 10 or less than 13.0 g/dl ( 130 g/l) for men and less than 12.0 g/dl ( 120 g/l) for women (WHO). Obesity is defined as body mass index of 30 kg/m 2 or greater. History of CVD in KEEP is defined as self-reported heart attack, heart bypass surgery, heart angioplasty, stroke, heart failure, abnormal heart rhythm, or peripheral arterial disease (survey form in use before May 2005). NHANES defined history of CVD (applicable only to participants 20 years) as self-reported history of coronary heart disease, angina/angina pectoris, heart attack, congestive heart failure, or stroke. Estimated glomerular filtration rate (egfr) was determined by using the isotope-dilution mass spectrometry 4-variable Modification of Diet in Renal Disease Study equation. CKD is defined as egfr less than 60 ml/min/1.73 m 2 ( 1.0 ml/s/1.73 m 2 ) and/or albumin-creatinine ratio of 30 mg/g or greater. 16 CKD stages were defined as follows: stage 1, egfr greater than 90 ml/min/1.73 m 2 ( 1.50 ml/s/1.73 m 2 ) and/or albumin-creatinine ratio of 30 mg/g or greater; stage 2, egfr of 60 to 89 ml/min/1.73 m 2 (1.00 to 1.48 ml/s/1.73 m 2 ) and/or albumin-creatinine ratio of 30 mg/g or greater; stage 3, egfr of 30 to 59 ml/min/1.73 m 2 (0.50 to 0.98 ml/s/1.73 m 2 ); stage 4, egfr of 15 to 29 ml/min/1.73 m 2 (0.25 to 0.48 ml/s/1.73 m 2 ); and stage 5, egfr less than 15 ml/min/1.73 m 2 ( 0.25 ml/s/1.73 m 2 ). Statistical Analysis Prevalence of anemia was analyzed with risk factors by using both the KDOQI and WHO definitions. Multiple logistic regression was used to determine the independent relationships between anemia outcome and associations, including age; sex; race; screening year; education; smoking status; personal history of diabetes, hypertension, or CVD; family history of diabetes or hypertension; obesity; and CKD. P less than 0.05 is considered statistically significant. RESULTS The population screened for the KEEP program included 70,069 eligible participants. data were collected for all participants and data for key variables were collected for 51,727 (73.8%). The NHANES cohort included 17,061 adult participants aged 18 years and older. Compared with NHANES, women and African Americans were overrepresented in KEEP. Of KEEP participants, 68.3% were women compared with 52% of NHANES participants (Table 1). Racial distribution in the KEEP popu-

3 S48 McFarlane et al Table 1. Prevalence by Risk Group: KEEP and NHANES KEEP NHANES * (%) (%) Characteristics No. of Participants % KDOQI WHO No. of Participants % KDOQI WHO Age (y) , , , , , , , , , , Sex Men 22, , Women 47, , Race/ethnicity White 32, , African American 23, , Other 13, , Non-Hispanic 61, , Hispanic 8, , Education High school 10, , High school 58, , Current smoker Yes 7, , No 58, , Obesity status Body mass index 30, , kg/m 2 Body mass index 38, , kg/m 2 diabetes Yes 18, , No 50, , hypertension Yes 36, , No 32, , cardiovascular disease Yes 13, , No 56, , Abbreviations: KEEP, Kidney Early Evaluation Program; NHANES, National Health and Nutrition Examination Survey; WHO, World Health Organization: KDOQI, Kidney Disease Outcomes Quality Initiative. *All analyses related to smoking status or cardiovascular disease are limited to participants 20 years and older. KDOQI: hemoglobin level less than 13.5 g/dl ( 135 g/l) for men and less than 12 g/dl ( 120 g/l) for women. WHO: hemoglobin level less than 13.0 g/dl ( 130 g/l) for men and less than 12 g/dl ( 120 g/l) for women. lation was 33.9% African American, 12.4% Hispanic, and 46.8% white. The NHANES population was 11.2% African American, 13.2% Hispanic, and 71.4% white. Because KEEP is a screening program targeted toward high-risk populations, KEEP data differ from NHANES data in prevalence of CKD risk factors. Prevalences of obesity, diabetes, hypertension, and CVD were greater for KEEP than NHANES participants: obesity, 44% versus 30.8%; diabetes, 26.8% versus 6.7%; hypertension, 53.5% versus 26.3%; and CVD, 19.9% versus 8.9%. Smoking and low education level (less than high school) were more prevalent in the NHANES

4 in CKD Data From KEEP and NHANES Population S49 Table 2. Mean Hemoglobin Values for KEEP and NHANES Participants by Sex and Racial Subgroups KEEP* (n 68,526) Hemoglobin (g/dl) NHANES (n 15,076) All Men Women White African American Other race Hispanic Non-Hispanic Note: KEEP values, mean SD; NHANES values, mean SE. To convert hemoglobin in g/dl to g/l, multiply by 10. Abbreviations: KEEP, Kidney Early Evaluation Program; NHANES, National Health and Nutrition Examination Survey. *In KEEP, all P for sex, race, and ethnicity study cohort than KEEP: smoking, 24.9% in NHANES versus 12.1% in KEEP, and low education level, 21.6% versus 15.5%. Using the KDOQI definition, the prevalence of anemia in KEEP participants was 2.2 times greater than in NHANES participants (13.9% versus 6.3%; Table 1). Greater anemia prevalence in KEEP was observed consistently across age and racial groups in both sexes and for each risk factor examined, including obesity, hypertension, diabetes, and CVD. (defined by KDOQI) was lower in current smokers compared with nonsmokers (KEEP, 9.8% versus 14.3%; NHANES, 3.6% versus 7.2%). Applying the WHO definition, results were similar, with anemia prevalence 2.2 times greater in the KEEP population than in the NHANES population (11.8% versus 5.3%). Results also were similar for smokers using the WHO anemia definition. Mean hemoglobin level was lower in KEEP (13.7 g/dl [137 g/l]) than NHANES participants (14.5 g/dl [145 g/l]; Table 2). KEEP mean hemoglobin values for patients with CKD by stage are significantly different (P 0.001), as follows: non-ckd, 13.8 g/dl (138 g/l); stage 1, 13.5 g/dl (135 g/l); stage 2, 13.7 g/dl (137 g/l); stage 3, 13.5 g/dl (135 g/l); stage 4, 12.2 g/dl (122 g/l); and stage 5, 11.3 g/dl (113 g/l). Smoking,, and CKD Using the KDOQI definition, anemia was less prevalent in current smokers in both the KEEP (8.6% for smokers, 12.6% for nonsmokers) and NHANES (14.0%, 25.3%) populations (Table 3). Results were similar using WHO anemia guidelines. The prevalence of anemia by smoking status for KEEP and NHANES is shown in Fig 1, and prevalence of anemia by CKD stages is shown in Fig 2. Sex Differences Using the KDOQI definition, anemia was more prevalent in KEEP men than women (15.5% versus 13.2%; Table 1). Conversely, using the WHO definition with a greater threshold for detection in men, the prevalence of anemia was greater in women than men (13.2% versus 8.9%). Men had greater hemoglobin values than women in both databases (KEEP, 14.7 g/dl [147 g/l] versus 13.2 g/dl [132 g/l]; NHANES, 15.4 g/dl [154 g/l] versus 13.6 g/dl [136 g/l]; Table 2). In participants with anemia, using the KDOQI definition, greater proportions of men than women had advanced CKD (KEEP, 35.1% versus 27.6%; NHANES, 28.2% versus 15.7%; Table 4). Results were similar using the WHO anemia guidelines. We used a multivariate logistic regression model that considered the odds of anemia in KEEP participants, a high-ckd-risk population. Using KDOQI guidelines, men had greater odds of anemia than women (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.23 to 1.37; P 0.001; Table 5). Conversely, using the WHO anemia definition, odds were lower for men than women (OR, 0.68; 95% CI, 0.64 to 0.72; P 0.001), reflecting the greater threshold of anemia detection in men, whereas the threshold for women was the same in the KDOQI and WHO definitions. Racial/Ethnic Differences Prevalences of anemia were greatest for African Americans in both the KEEP and NHANES cohorts (Table 1). In KEEP participants, using the KDOQI definition, prevalences of anemia were 21.7% for African Americans, 9.9% for whites, and 9.1% for Hispanics. NHANES data also showed a greater prevalence of anemia in African Americans. A similar pattern of racial

5 S50 McFarlane et al Table 3. Characteristics Distribution by Status: KEEP and NHANES KEEP NHANES * KDOQI WHO KDOQI WHO No No No No No. of participants 9,747 60,322 8,288 61,781 1,480 13,596 1,260 13,816 Age (y) Sex Men Women Race/ethnicity White African American Other Non-Hispanic Hispanic Education High school High school Current smoker Yes No Obesity status Body mass index kg/m 2 Body mass index kg/m 2 diabetes Yes No hypertension Yes No cardiovascular disease Yes No Note: Categorical values are expressed in percent. Abbreviations: KEEP, Kidney Early Evaluation Program; NHANES, National Health and Nutrition Examination Survey; WHO, World Health Organization: KDOQI, Kidney Disease Outcomes Quality Initiative. *All analyses related to smoking status or cardiovascular disease limited to participants aged 20 years or older. KDOQI: hemoglobin level less than 13.5 g/dl ( 135 g/l) for men and less than 12 g/dl ( 120 g/l) for women. WHO: hemoglobin level less than 13.0 g/dl ( 130 g/l) for men and less than 12 g/dl ( 120 g/l) for women. distribution was observed using WHO anemia criteria. Mean hemoglobin values were lowest in African Americans compared with other racial and ethnic groups in both KEEP and NHANES databases (Table 2), whereas values for Hispanics and whites were similar. In the KEEP cohort, average hemoglobin levels were 13.2 g/dl (132 g/l) for African Americans, 14.0 g/dl (140 g/l) for Hispanics, and 14.0 g/dl (140 g/l) for whites.

6 in CKD Data From KEEP and NHANES Population S51 WHO K/DOQI Figure 1. Prevalence of anemia by smoking status. Abbreviations: NHANES, National Health and Nutrition Examination Survey; KEEP, Kidney Early Evaluation Program; WHO, World Health Organization: KDOQI, Kidney Disease Outcomes Quality Initiative. Prevalence of anemia (%) Current smoker Nonsmoker Current smoker Nonsmoker KEEP NHANES Similarly, in the NHANES cohort, hemoglobin levels were 13.6 g/dl (136 g/l) for African Americans, 14.6 g/dl (146 g/l) for Hispanics, and 14.6 g/dl (146 g/l) for whites. In anemic KEEP participants, using the KDOQI definition, 52.5% were African American, 32.9% were white, and 8.1% were Hispanic (Table 3). Conversely, in anemic NHANES participants, 50.1% were white, 31.5% were African American, and 13.2% were Hispanic. This reflects the overrepresentation of African Americans in KEEP compared with NHANES. Results were similar using the WHO anemia guidelines. Compared with whites, African Americans in KEEP had greater odds of anemia (OR, 2.98; 95% CI, 2.80 to 3.16; P for KDOQI criteria; OR, 3.00; 95% CI, 2.81 to 3.20; P for WHO criteria; Table 5). Compared with non-hispanics, Hispanic participants had lower odds of anemia (OR, 0.79; 95% CI, 0.70 to 0.88; P 0.01 for KDOQI criteria; OR, 0.80; 95% CI, 0.71 to 0.90; P for WHO criteria). Other Factors Associated With in the KEEP Population A greater proportion of advanced CKD (stages 3 to 5) was observed in anemic patients of all racial groups and various risk factors. However, it was not observed in the youngest KEEP age group (18 to 30 years), in which the prevalence of stage 1 CKD was greater (stage 1, 9.3%; stage 2, 2.4%; and stages 3 to 5, 3.0%; Table 4). Corresponding data were not available for the NHANES population because of unreliable estimates. Compared with the age group with the highest number of participants (ages 46 to 60 years), both younger and older age categories had greater odds of anemia by using the KDOQI definition, with the greatest odds observed in the WHO K/DOQI Prevalence of anemia (%) Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 CKD stages Figure 2. Prevalence of anemia by chronic kidney disease (CKD) stage in Kidney Early Evaluation Program. Abbreviations: WHO, World Health Organization: KDOQI, Kidney Disease Outcomes Quality Initiative.

7 Table 4. Prevalence of Chronic Kidney Disease Stages in Anemic Patients by Characteristics: KEEP and NHANES KDOQI* WHO S52 KEEP NHANES KEEP NHANES Chronic Kidney Disease Stage Chronic Kidney Disease Stage Chronic Kidney Disease Stage Chronic Kidney Disease Stage Characteristic None None None None No. of participants 5, , , , Age (y) NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR Sex Men NR NR Women Race/ethnicity White NR NR African American Others NR NR NR NR NR Non-Hispanic Hispanic NR NR NR NR NR NR Education High school High school Current smoker Yes NR NR NR 14.2 No Obesity status Body mass index 30 kg/m Body mass index 30 kg.m diabetes Yes NR NR No hypertension Yes No cardiovascular disease Yes NR NR NR NR 61.7 No Abbreviations: KEEP, Kidney Early Evaluation Program; NHANES, National Health and Nutrition Examination Survey; WHO, World Health Organization: KDOQI, Kidney Disease Outcomes Quality Initiative; NR, estimates not reliable. *KDOQI: hemoglobin level less than 13.5 g/dl ( 135 g/l) for men and less than 12 g/dl ( 120 g/l) for women. WHO: hemoglobin level less than 13.0 g/dl ( 130 g/l) for men and less than 12 g/dl ( 120 g/l) for women. McFarlane et al

8 in CKD Data From KEEP and NHANES Population S53 Table 5. Odds of From Multivariable Logistic Regressions: KEEP KDOQI* WHO Odds Ratio (95% confidence interval) P Odds Ratio (95% confidence interval) P Age (y) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Sex Women 1 1 Men 1.30 ( ) ( ) Race/ethnicity White 1 1 African American 2.98 ( ) ( ) Other 1.39 ( ) ( ) Non-Hispanic 1 1 Hispanic 0.79 ( ) ( ) Current smoker 0.63 ( ) ( ) Education high school 0.87 ( ) ( ) diabetes 1.73 ( ) ( ) hypertension 1.07 ( ) ( ) 0.06 cardiovascular disease 1.29 ( ) ( ) Family history of diabetes 1.02 ( ) ( ) 0.5 Family history of hypertension 0.95 ( ) ( ) 0.4 Body mass index 30 kg/m ( ) ( ) 0.9 Chronic kidney disease 1.73 ( ) ( ) Cohort year ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 0.3 Note: n 51,727. All listed variables are in the multivariable logistic regression. For example, analysis of cohort year is adjusted for other variables in the table. Abbreviations: KEEP, Kidney Early Evaluation Program; NHANES, National Health and Nutrition Examination Survey; WHO, World Health Organization: KDOQI, Kidney Disease Outcomes Quality Initiative. *KDOQI: hemoglobin level less than 13.5 g/dl ( 135 g/l) for men and less than 12 g/dl ( 120 g/l) for women. WHO: hemoglobin level less than 13.0 g/dl ( 130 g/l) for men and less than 12 g/dl ( 120 g/l) for women. oldest age group (age 75 years; OR, 2.20; 95% CI, 2.00 to 2.42; P 0.01; Table 5). Results were similar using WHO criteria. Other risk factors that significantly increased the odds of anemia included lower educational level, diabetes mellitus, hypertension, CVD, and CKD, with risk greatest for patients with diabetes and CKD (OR, 1.73; 95% CI, 1.63 to 1.83; P for patients with diabetes; OR, 1.73; 95% CI, 1.63 to 1.84; P for patients with CKD) using KDOQI guidelines. Results were similar using the WHO anemia definition (Table 5). DISCUSSION Our study highlights several major differences between a targeted community-based screening program (KEEP) and a generalizable population health survey (NHANES ). Greater percentages of KEEP participants were at risk of CKD and anemia, including African Americans, who were 3 times more prevalent in KEEP than NHANES. Risk factors for CKD and CVD 5,9,14 also were better represented in KEEP populations than in NHANES. For example, obesity was 1.4 times; hypertension was 2 times; and

9 S54 diabetes was 4 times more prevalent in KEEP than NHANES. Not surprisingly, the KEEP population had a greater rate of CKD, with an associated much greater prevalence of anemia; this value was 2.2 times greater than in the NHANES sample population. The greater prevalence of anemia observed in the KEEP cohort was consistent across sex, racial and ethnic groups, and CVD risk categories, except for smoking. The high prevalence of diabetes observed in the KEEP cohort, 26.8% compared with 6.7% in the NHANES sample population, likely is a major contributor to the greater prevalence of anemia in KEEP participants through its effect on risk of CKD and other mechanisms. 4 is common in patients with diabetes and often goes unrecognized and untreated Although egfr and iron stores are the strongest predictors of hemoglobin levels in patients with diabetes, these factors do not fully account for the increased prevalence of anemia in the diabetic population. 4,19 Other factors, such as absolute and/or relative erythropoietin deficiency, inflammation, and oxidative stress, may explain the development of anemia in patients with diabetes and CKD. Furthermore, accumulating evidence indicates that in patients with early diabetic nephropathy, anemia is a common finding and associated with erythropoietin deficiency. 4,17 Although men had greater hemoglobin values than women, they also had greater rates of more advanced CKD. The KDOQI definition with a lower threshold for anemia detection in men (13.5 g/dl [135 g/l]) thus was more reflective of the severity of CKD observed in men, resulting in a 30% greater risk of anemia in men than women. This is in contrast to the WHO anemia definition, with a lower hemoglobin cutoff value for men (13.0 g/dl [130 g/l]) or a greater threshold for diagnosing anemia in men, which reversed the odds of anemia between sexes; women had a 32% greater risk of anemia than men using WHO criteria. The greater prevalence of anemia in participants older than 60 years compared with those aged 46 to 60 years likely is a reflection of a greater rate of CKD in older participants and lower egfrs with aging. 20 Conversely, the greater risk of anemia in younger KEEP participants may represent mechanisms of anemia other than CKD, given the lower prevalence and less severe CKD in younger participants. It also could reflect higher representation of women and African Americans, groups with a greater risk of anemia independent of CKD. 12,13 The lower prevalence of anemia in current smokers in both the KEEP and NHANES populations is consistent with previous data indicating greater hemoglobin levels in smokers caused by secondary erythrocytosis. 21 Cigarette smoking appears to cause a generalized upward shift of the hemoglobin distribution curve, thus decreasing the utility of hemoglobin levels to detect anemia in smokers. 22 Treatment of anemia is by identification of underlying cause, which, in patients with CKD, may be either functional or actual iron deficiency with or without erythropoietic hormone resistance or deficiency. 23 KEEP data include insufficient specific medication data to address anemia treatment in this study. Findings from our study have potentially significant public health implications. Early recognition of anemia through a targeted screening program for populations at high risk of CKD may become important for the development of preventive and therapeutic strategies. Decreased working capacity, cognitive impairment, angina, and cardiorenal anemia syndrome, a triad of worsening anemia, worsening CKD, and worsening congestive heart failure, are potential consequences of anemia of CKD. 24 ACKNOWLEDGEMENTS McFarlane et al In addition to the authors listed, the Kidney Early Evaluation Program (KEEP) Investigators are Dennis Andress, MD, David Calhoun, MD, Bruce Johnson, MD, Claudine T. Jurkovitz, MD, MPH, Chamberlain I. Obialo, MD, Lesley A. Stevens, MD, and Michael G. Shlipak, MD. The authors thank Shane Nygaard, BA, and Nan Booth, MSW, MPH of the Chronic Disease Research Group for manuscript preparation and manuscript editing, respectively. Support: KEEP is a program of the National Kidney Foundation Inc and is supported by Amgen, Abbott, Genzyme, Ortho Biotech Products LP, and Novartis, with additional support provided by Siemens Medical Solutions Diagnostics, Lifescan, Suplena, and OceanSpray Cranberries. Financial Disclosure: Dr Vassalotti reports having received grant support from the Centers for Disease Control and Prevention, but has no conflicts of interest with the subject of this article. Dr Collins has received research support from Amgen. The other authors have no conflicts of interest with the subject matter of this manuscript.

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