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Prevalence and Associations of Anemia of CKD: Kidney Early EvaluationProgram (KEEP) and National Health and Nutrition Examination Survey

(NHANES) 1999-2004

Samy I. McFarlane, MD, MPH,1 Shu-Cheng Chen, MS,2 Adam T. Whaley-Connell, MD,3

James R. Sowers, MD,3 Joseph A. Vassalotti, MD,4,5 Moro O. Salifu, MD, MPH,1 Suying Li, PhD,2

Changchun Wang, MS,2 George Bakris, MD,6 Peter A. McCullough, MD, MPH,7 Allan J. Collins, MD,2

and Keith C. Norris, MD,8,9 on behalf of the Kidney Early Evaluation Program Investigators

Background: Early identification of anemia of chronic kidney disease may be important for thedevelopment of preventive strategies. We compared anemia prevalence and characteristics in theNational Kidney Foundation Kidney Early Evaluation Program (KEEP) and National Health and NutritionExamination Survey (NHANES) 1999-2004 populations.

Methods: Clinical, demographic, and laboratory data were collected from August 2000 to December31, 2006, from participants in KEEP, a community-based health-screening program targeting individu-als 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, orhypertension. Anemia was defined as hemoglobin level less than 13.5 g/dL for men and less than 12.0g/dL for women (Kidney Disease Outcomes Quality Initiative [KDOQI] 2006) or less than 13.0 g/dL formen 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% ofparticipants, were women. African Americans represented 33.9% of the KEEP and 11.2% of theNHANES cohorts, and Hispanics comprised 12.4% of KEEP and 13.2% of NHANES. Using the KDOQIclassification, anemia was present in 13.9% and 6.3% of KEEP and NHANES participants, whereasusing the WHO classification, anemia was present in 11.8% and 5.3%, respectively. In adjusted analysisof 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 whiteKEEP participants (OR, 2.98; 95% CI, 2.80 to 3.16; OR, 3.00; 95% CI, 2.81 to 3.20 for KDOQI- andWHO-defined anemia, respectively).

Conclusion: Anemia was twice as common in the targeted KEEP chronic kidney disease screeningprogram cohort than in the NHANES sample population. African Americans had a 3-fold increasedlikelihood of anemia compared with whites. Targeted screening can identify anemia in a high-riskpopulation.Am J Kidney Dis 51(S2):S46-S55. © 2008 by the National Kidney Foundation, Inc.

INDEX WORDS: Anemia; chronic kidney disease; diabetes; race; sex.

Ailtpt

hronic kidney disease (CKD) is highlyprevalent in the US population, with re-

ent estimates indicating that up to 16.5% ofeople aged 20 years or older have the disease.1

frican Americans and other racial and ethnicinority groups are at increased risk of CKD.2,3

From the 1Division of Endocrinology, SUNY-Downstate andings County Hospital Centers, Brooklyn, NY; 2Chronic Dis-ase Research Group, Minneapolis Medical Research Founda-ion, Minneapolis, MN; 3University of Missouri-Columbiachool of Medicine, Columbia, MO; 4National Kidney Founda-ion; 5Department of Medicine, Division of Nephrology, Mountinai School of Medicine, New York, NY; 6Hypertensive Dis-ases Unit, Section of Endocrinology, Diabetes and Metabo-ism, University of Chicago, Pritzker School of Medicine,hicago, IL; 7Department of Medicine, Divisions of Cardiol-gy, Nutrition and Preventive Medicine, William Beaumontospital, Royal Oak, MI; 8Charles R. Drew University of

9

edicine and Science; and David Geffen School of Medicine,

American Journal of Kidney46

nemia is a common complication of CKD ands associated with increased risk of cardiovascu-ar disease (CVD), morbidity, and mortality, par-icularly in high-risk populations.4,5 CVD risk inatients with CKD involves traditional and non-raditional risk factors.4-9 Traditional risk factors

niversity of California, Los Angeles, CA.Received November 21, 2007. Accepted in revised form

ecember 28, 2007.A list of the members of the Kidney Early Evaluation

rogram Investigators appears at the end of this article.Address correspondence to Samy I. McFarlane, MD,PH, Department of Medicine, Box 50, State University ofew York, Health Science Center at Brooklyn, Kings Countyospital Center, 450 Clarkson Ave, Brooklyn, NY 11203.-mail: smcfarlane@downstate.edu© 2008 by the National Kidney Foundation, Inc.0272-6386/08/5104-0107$34.00/0

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doi:10.1053/j.ajkd.2007.12.019

Diseases, Vol 51, No 4, Suppl 2 (April), 2008: pp S46-S55

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Anemia in CKD Data From KEEP and NHANES Population S47

nclude diabetes, hypertension, obesity, dyslipi-emia, smoking, and advanced age.8 Nontradi-ional risk factors include hyperhomocysteine-ia, hyperparathyroidism, hyperphosphatemia,

ndothelial dysfunction, diastolic dysfunction,nd anemia, which is increasingly recognized inhis patient population.6,7,9 Anemia of CKD gen-rally is attributed to absolute or relative erythro-oietin deficiency. However, other factors, suchs iron deficiency, blood loss, shortened redlood cell life span, and inflammation, may con-ribute to its development.10,11

In the general population, anemia is morerevalent and severe in African Americans thanhites.12,13 Although racial and ethnic differ-

nces in anemia prevalence and severity wereoted in patients with CKD,14 the extent andharacteristics of anemia in populations at risk ofKD are less well defined. Early identification ofnemia, particularly in high-risk populations,ould lead to effective preventive and therapeu-ic strategies to improve outcomes. Thus, betternderstanding of the characteristics of this popu-ation has potential public health benefits. Wexamined the prevalence and associations ofnemia in participants in the Kidney Early Evalu-tion Program (KEEP), a large free community-ased CKD screening program, and comparedhem with the National Health and Nutritionxamination Survey (NHANES) 1999-2004, a

epresentative sample of the US general popula-ion. KEEP targets high-risk populations; eli-ible participants are 18 years or older and havepersonal or family history of diabetes or hyper-

ension or a family history of kidney disease.onversely, NHANES 1999-2004 surveys were

argeted toward randomized cohorts that are gen-ralizable to the US population.

The objectives of this study are to: (1) assesshe prevalence of anemia in the KEEP andHANES populations by risk groups, including

ge, sex, race, diabetes, and CVD, by usingational Kidney Foundation Kidney Disease Out-

omes Quality Initiative (KDOQI) and Worldealth Organization (WHO) anemia definitions;

2) assess the prevalence of CKD stages in ane-ic patients across the different risk groups in

he KEEP and NHANES cohorts; and (3) iden-ify factors associated with significant odds ofnemia in the CKD high-risk population of the

EEP program. (

METHODS

efinitions

KEEP and the NHANES database are fully describedlsewhere in this supplement.15 Disease definitions are asollows. History of diabetes is defined as self-reported diabe-es or retinopathy, and history of hypertension, as self-eported hypertension. Anemia is defined as hemoglobinevel less than 13.5 g/dL (�135 g/L) for men and less than2.0 g/dL (�120 g/L) for women (KDOQI 2006)10 or lesshan 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 bodyass index of 30 kg/m2 or greater. History of CVD in KEEP

s defined as self-reported heart attack, heart bypass surgery,eart angioplasty, stroke, heart failure, abnormal hearthythm, or peripheral arterial disease (survey form in useefore May 2005). NHANES defined history of CVD (appli-able only to participants �20 years) as self-reported historyf coronary heart disease, angina/angina pectoris, heartttack, congestive heart failure, or stroke. Estimated glomer-lar filtration rate (eGFR) was determined by using thesotope-dilution mass spectrometry 4-variable Modificationf Diet in Renal Disease Study equation. CKD is defined asGFR less than 60 mL/min/1.73 m2 (�1.0 mL/s/1.73 m2)nd/or albumin-creatinine ratio of 30 mg/g or greater.16

KD stages were defined as follows: stage 1, eGFR greaterhan 90 mL/min/1.73 m2 (�1.50 mL/s/1.73 m2) and/orlbumin-creatinine ratio of 30 mg/g or greater; stage 2,GFR of 60 to 89 mL/min/1.73 m2 (1.00 to 1.48 mL/s/1.732) and/or albumin-creatinine ratio of 30 mg/g or greater;

tage 3, eGFR of 30 to 59 mL/min/1.73 m2 (0.50 to 0.98L/s/1.73 m2); stage 4, eGFR of 15 to 29 mL/min/1.73 m2

0.25 to 0.48 mL/s/1.73 m2); and stage 5, eGFR less than 15L/min/1.73 m2 (�0.25 mL/s/1.73 m2).

tatistical Analysis

Prevalence of anemia was analyzed with risk factors bysing both the KDOQI and WHO definitions. Multipleogistic regression was used to determine the independentelationships between anemia outcome and associations,ncluding age; sex; race; screening year; education; smokingtatus; personal history of diabetes, hypertension, or CVD;amily history of diabetes or hypertension; obesity; andKD. P less than 0.05 is considered statistically significant.

RESULTS

The population screened for the KEEP pro-ram included 70,069 eligible participants. Ane-ia data were collected for all participants and

ata for key variables were collected for 51,72773.8%). The NHANES 1999-2004 cohort in-luded 17,061 adult participants aged 18 yearsnd older. Compared with NHANES, womennd African Americans were overrepresented inEEP. Of KEEP participants, 68.3% were women

ompared with 52% of NHANES participants

Table 1). Racial distribution in the KEEP popu-

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McFarlane et alS48

ation was 33.9% African American, 12.4% His-anic, and 46.8% white. The NHANES popula-ion was 11.2% African American, 13.2%ispanic, and 71.4% white. Because KEEP is a

creening program targeted toward high-riskopulations, KEEP data differ from NHANES

Table 1. Anemia Prevalence by Ris

KEEP

A

Characteristics No. of Participants % KDOQ

ge (y)18-30 5,582 8.0 10.31-45 15,729 22.5 13.46-60 24,617 35.1 11.61-75 18,238 26.0 15.�75 5,903 8.4 24.

exMen 22,214 31.7 15.Women 47,855 68.3 13.ace/ethnicityWhite 32,096 46.8 9.African American 23,200 33.9 21.Other 13,223 19.3 10.Non-Hispanic 61,385 86.8 14.Hispanic 8,684 13.2 9.

ducation�High school 10,679 15.5 16.�High school 58,318 84.5 13.urrent smokerYes 7,952 12.1 9.No 58,029 88.0 14.besity statusBody mass index

� 30 kg/m230,317 44.0 14.

Body mass index� 30 kg/m2

38,579 56.0 13.

elf-reporteddiabetes

Yes 18,586 26.8 19.No 50,773 73.2 11.

elf-reportedhypertension

Yes 36,883 53.5 16.No 32,023 46.5 11.

elf-reportedcardiovasculardisease

Yes 13,912 19.9 18.No 56,157 80.2 12.

Abbreviations: KEEP, Kidney Early Evaluation ProgramHO, World Health Organization: KDOQI, Kidney Disease*All analyses related to smoking status or cardiovascular†KDOQI: hemoglobin level less than 13.5 g/dL (�135 g/L‡WHO: hemoglobin level less than 13.0 g/dL (�130 g/L)

ata in prevalence of CKD risk factors. Preva- s

ences of obesity, diabetes, hypertension, andVD were greater for KEEP than NHANESarticipants: obesity, 44% versus 30.8%; diabe-es, 26.8% versus 6.7%; hypertension, 53.5%ersus 26.3%; and CVD, 19.9% versus 8.9%.moking and low education level (less than high

up: KEEP and NHANES 1999-2004

NHANES 1999-2004*

%) Anemia (%)

WHO‡ No. of Participants % KDOQI† WHO‡

9.3 4,285 23.9 4.8 4.611.9 3,496 30.6 5.9 5.19.8 2,813 25.1 5.0 4.2

12.7 2,872 13.8 7.9 5.720.0 1,610 6.5 15.7 13.0

8.9 7,194 48.0 4.9 2.813.2 7,882 52.0 7.6 7.6

8.0 7,305 71.4 4.4 3.519.0 3,027 11.2 18.5 16.29.1 4,744 17.5 6.8 6.1

12.4 10,770 13.2 6.3 5.38.0 4,306 6.3 5.8

14.1 5,144 21.6 8.6 7.511.4 9,903 78.4 5.7 4.7

7.8 2,940 24.9 3.6 2.912.3 10,553 75.1 7.2 6.1

13.1 4,555 30.8 6.8 6.0

10.9 10,111 69.2 5.8 4.8

16.9 1,346 6.7 15.1 12.69.97 13,723 93.3 5.7 4.8

13.6 4,333 26.3 8.5 7.19.9 10,553 73.7 5.5 4.7

15.8 1,559 8.9 13.2 10.210.9 11,888 91.1 5.7 4.9

NES, National Health and Nutrition Examination Survey;mes Quality Initiative.e are limited to participants 20 years and older.en and less than 12 g/dL (�120 g/L) for women.n and less than 12 g/dL (�120 g/L) for women.

k Gro

nemia (

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52

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74

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chool) were more prevalent in the NHANES

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Anemia in CKD Data From KEEP and NHANES Population S49

tudy cohort than KEEP: smoking, 24.9% inHANES versus 12.1% in KEEP, and low educa-

ion level, 21.6% versus 15.5%.Using the KDOQI definition, the prevalence

f anemia in KEEP participants was 2.2 timesreater than in NHANES participants (13.9%ersus 6.3%; Table 1). Greater anemia preva-ence in KEEP was observed consistently acrossge and racial groups in both sexes and forach risk factor examined, including obesity,ypertension, diabetes, and CVD. Anemia (de-ned by KDOQI) was lower in current smok-rs compared with nonsmokers (KEEP, 9.8%ersus 14.3%; NHANES, 3.6% versus 7.2%).pplying the WHO definition, results were

imilar, with anemia prevalence 2.2 timesreater in the KEEP population than in theHANES population (11.8% versus 5.3%).esults also were similar for smokers using theHO anemia definition.Mean hemoglobin level was lower in KEEP

13.7 g/dL [137 g/L]) than NHANES partici-ants (14.5 g/dL [145 g/L]; Table 2). KEEP meanemoglobin values for patients with CKD bytage are significantly different (P � 0.001), asollows: non-CKD, 13.8 g/dL (138 g/L); stage 1,3.5 g/dL (135 g/L); stage 2, 13.7 g/dL (137/L); stage 3, 13.5 g/dL (135 g/L); stage 4, 12.2

Table 2. Mean Hemoglobin Values for KEEP andNHANES 1999-2004 Participants by Sex

and Racial Subgroups

Hemoglobin (g/dL)

KEEP*(n � 68,526)

NHANES 1999-2004(n � 15,076)

ll 13.7 � 1.5 14.5 � 0.05en 14.7 � 1.4 15.4 � 0.05omen 13.2 � 1.4 13.6 � 0.05hite 14.0 � 1.4 14.6 � 0.04frican American 13.2 � 1.6 13.6 � 0.03ther race 13.9 � 1.5 14.5 � 0.07ispanic 14.0 � 1.5 14.6 � 0.08on-Hispanic 13.7 � 1.5 14.5 � 0.05

Note: KEEP values, mean � SD; NHANES values,ean � SE. To convert hemoglobin in g/dL to g/L, multiplyy 10.Abbreviations: KEEP, Kidney Early Evaluation Program;HANES, National Health and Nutrition Examination Sur-ey.*In KEEP, all P for sex, race, and ethnicity � 0.001.

/dL (122 g/L); and stage 5, 11.3 g/dL (113 g/L). A

moking, Anemia, andCKD

Using the KDOQI definition, anemia was lessrevalent in current smokers in both the KEEP8.6% for smokers, 12.6% for nonsmokers) andHANES (14.0%, 25.3%) populations (Table 3).esults were similar using WHO anemia guide-

ines. The prevalence of anemia by smokingtatus for KEEP and NHANES is shown in Fig 1,nd prevalence of anemia by CKD stages ishown in Fig 2.

exDifferences

Using the KDOQI definition, anemia was morerevalent in KEEP men than women (15.5%ersus 13.2%; Table 1). Conversely, using theHO definition with a greater threshold for

etection in men, the prevalence of anemia wasreater in women than men (13.2% versus 8.9%).en had greater hemoglobin values than women

n both databases (KEEP, 14.7 g/dL [147 g/L]ersus 13.2 g/dL [132 g/L]; NHANES, 15.4 g/dL154 g/L] versus 13.6 g/dL [136 g/L]; Table 2).n participants with anemia, using the KDOQIefinition, greater proportions of men than womenad advanced CKD (KEEP, 35.1% versus 27.6%;HANES, 28.2% versus 15.7%; Table 4). Resultsere similar using the WHO anemia guidelines.We used a multivariate logistic regressionodel that considered the odds of anemia inEEP participants, a high-CKD-risk population.sing KDOQI guidelines, men had greater oddsf anemia than women (odds ratio [OR], 1.30;5% confidence interval [CI], 1.23 to 1.37; P �.001; Table 5). Conversely, using the WHOnemia definition, odds were lower for men thanomen (OR, 0.68; 95% CI, 0.64 to 0.72; P �.001), reflecting the greater threshold of anemiaetection in men, whereas the threshold foromen was the same in the KDOQI and WHOefinitions.

acial/EthnicDifferences

Prevalences of anemia were greatest for Afri-an Americans in both the KEEP and NHANESohorts (Table 1). In KEEP participants, usinghe KDOQI definition, prevalences of anemiaere 21.7% for African Americans, 9.9% forhites, and 9.1% for Hispanics. NHANES data

lso showed a greater prevalence of anemia in

frican Americans. A similar pattern of racial

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McFarlane et alS50

istribution was observed using WHO anemiariteria.

Mean hemoglobin values were lowest in Afri-an Americans compared with other racial and

Table 3. Characteristics Distributio

KEEP

KDOQI† W

AnemiaNo

Anemia Anemia

o. of participants 9,747 60,322 8,288ge (y)18-30 5.9 8.3 6.331-45 21.1 22.7 22.546-60 29.2 36.1 29.061-75 29.2 25.5 28.0�75 14.5 7.4 14.2

exMen 35.2 31.1 23.8Women 64.8 68.9 76.2ace/ethnicityWhite 32.9 49.1 31.3African American 52.5 30.8 53.9Other 14.6 20.1 14.8Non-Hispanic 91.9 86.9 91.7Hispanic 8.1 13.1 8.3

ducation�High school 18.6 15.0 18.4�High school 81.4 85.0 81.6urrent smokerYes 8.6 12.6 8.0No 91.4 87.4 92.0besity statusBody mass index

� 30 kg/m247.0 43.5 48.6

Body mass index� 30 kg/m2

53.1 56.5 51.4

elf-reporteddiabetes

Yes 38.4 24.9 38.4No 61.6 75.1 61.6

elf-reportedhypertension

Yes 61.8 52.2 61.5No 38.2 47.8 38.5

elf-reportedcardiovasculardisease

Yes 26.7 18.8 26.5No 73.3 81.3 73.5

Note: Categorical values are expressed in percent.Abbreviations: KEEP, Kidney Early Evaluation ProgramHO, World Health Organization: KDOQI, Kidney Disease*All analyses related to smoking status or cardiovascular†KDOQI: hemoglobin level less than 13.5 g/dL (�135 g/L‡WHO: hemoglobin level less than 13.0 g/dL (�130 g/L)

thnic groups in both KEEP and NHANES data- f

ases (Table 2), whereas values for Hispanicsnd whites were similar. In the KEEP cohort,verage hemoglobin levels were 13.2 g/dL (132/L) for African Americans, 14.0 g/dL (140 g/L)

nemia Status: KEEP and NHANES

NHANES 1999-2004*

KDOQI† WHO‡

Noemia Anemia

NoAnemia Anemia

NoAnemia

781 1,480 13,596 1,260 13,816

8.2 17.9 23.8 20.0 23.622.4 28.6 30.9 29.2 30.936.0 20.0 25.8 20.1 25.725.8 17.4 13.7 15.0 13.97.7 16.1 5.8 15.7 5.9

32.8 37.0 48.8 25.4 49.367.2 63.0 51.2 74.6 50.7

49.0 50.1 73.5 47.6 73.431.1 31.5 9.4 32.6 9.519.9 18.4 17.1 19.8 17.087.1 86.8 86.8 85.6 86.912.9 13.2 13.2 14.4 13.1

15.1 29.0 20.7 29.8 20.784.9 71.0 79.3 70.2 79.3

12.6 14.0 25.3 13.2 25.287.4 86.0 74.7 86.8 74.8

43.4 34.6 30.5 35.8 30.5

56.6 65.4 69.5 64.2 69.5

25.2 16.1 6.1 16.0 6.274.8 83.9 93.9 84.0 93.8

52.5 35.8 26.0 35.3 26.147.5 64.2 74.0 64.7 73.9

19.0 18.5 8.2 16.9 8.481.0 81.5 91.8 83.1 91.6

NES, National Health and Nutrition Examination Survey;mes Quality Initiative.e limited to participants aged 20 years or older.en and less than 12 g/dL (�120 g/L) for women.n and less than 12 g/dL (�120 g/L) for women.

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Anemia in CKD Data From KEEP and NHANES Population S51

imilarly, in the NHANES cohort, hemoglobinevels were 13.6 g/dL (136 g/L) for Africanmericans, 14.6 g/dL (146 g/L) for Hispanics,

nd 14.6 g/dL (146 g/L) for whites.In anemic KEEP participants, using the

DOQI definition, 52.5% were African Ameri-an, 32.9% were white, and 8.1% were HispanicTable 3). Conversely, in anemic NHANES par-icipants, 50.1% were white, 31.5% were Africanmerican, and 13.2% were Hispanic. This re-ects the overrepresentation of African Ameri-ans in KEEP compared with NHANES. Resultsere similar using the WHO anemia guidelines.Compared with whites, African Americans in

EEP had greater odds of anemia (OR, 2.98;5% CI, 2.80 to 3.16; P � 0.001 for KDOQIriteria; OR, 3.00; 95% CI, 2.81 to 3.20; P �.001 for WHO criteria; Table 5). Comparedith non-Hispanics, Hispanic participants had

ower odds of anemia (OR, 0.79; 95% CI, 0.70 to

0

2

4

6

8

10

12

14

16

Pre

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ane

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Figure 1. Prevalence of anemia by smokingtatus. Abbreviations: NHANES, National Healthnd Nutrition Examination Survey; KEEP, Kid-ey Early Evaluation Program; WHO, Worldealth Organization: KDOQI, Kidney Diseaseutcomes Quality Initiative.

0

10

20

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50

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CKD stages

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ther FactorsAssociatedWithAnemia in theEEPPopulation

A greater proportion of advanced CKD (stagesto 5) was observed in anemic patients of all

acial groups and various risk factors. However,t was not observed in the youngest KEEP ageroup (18 to 30 years), in which the prevalencef stage 1 CKD was greater (stage 1, 9.3%; stage, 2.4%; and stages 3 to 5, 3.0%; Table 4).orresponding data were not available for theHANES population because of unreliable esti-ates. Compared with the age group with the

ighest number of participants (ages 46 to 60ears), both younger and older age categoriesad greater odds of anemia by using the KDOQIefinition, with the greatest odds observed in the

12.3

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14.3

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sm oker Nonsm oker Current sm oker Nonsm oker

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Figure 2. Prevalence of anemia by chronickidney disease (CKD) stage in Kidney EarlyEvaluation Program. Abbreviations: WHO, WorldHealth Organization: KDOQI, Kidney Disease

7.8

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85.4

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Anemia in CKD Data From KEEP and NHANES Population S53

ldest age group (age � 75 years; OR, 2.20; 95%I, 2.00 to 2.42; P � 0.01; Table 5). Resultsere similar using WHO criteria.Other risk factors that significantly increased

he odds of anemia included lower educationalevel, diabetes mellitus, hypertension, CVD, andKD, with risk greatest for patients with diabe-

es and CKD (OR, 1.73; 95% CI, 1.63 to 1.83; P0.001 for patients with diabetes; OR, 1.73;

5% CI, 1.63 to 1.84; P � 0.001 for patients withKD) using KDOQI guidelines. Results were

imilar using the WHO anemia definition

Table 5. Odds of Anemia From Mu

Odds Ratio (9confidence int

ge (y)18-30 1.17 (1.04-1.31-45 1.35 (1.25-1.46-60 161-75 1.23 (1.14-1.�75 2.20 (2.001-2

exWomen 1Men 1.30 (1.23-1.ace/ethnicityWhite 1African American 2.98 (2.80-3.Other 1.39 (1.27-1.Non-Hispanic 1Hispanic 0.79 (0.70-0.urrent smoker 0.63 (0.58-0.ducation � high school 0.87 (0.81-0.elf-reported diabetes 1.73 (1.63-1.elf-reported hypertension 1.07 (1.01-1.elf-reported cardiovascular disease 1.29 (1.22-1.amily history of diabetes 1.02 (1.00-1.amily history of hypertension 0.95 (0.89-1.ody mass index � 30 kg/m2 0.99 (0.94-1.hronic kidney disease 1.73 (1.63-1.ohort year2000-2001 12002 1.14 (0.93-1.2003 0.95 (0.77-1.2004 1.14 (0.94-1.2005 1.02 (0.83-1.2006 1.10 (0.90-1.

Note: n � 51,727. All listed variables are in the multivardjusted for other variables in the table.Abbreviations: KEEP, Kidney Early Evaluation ProgramHO, World Health Organization: KDOQI, Kidney Disease*KDOQI: hemoglobin level less than 13.5 g/dL (�135 g/L†WHO: hemoglobin level less than 13.0 g/dL (�130 g/L)

Table 5). w

DISCUSSION

Our study highlights several major differencesetween a targeted community-based screeningrogram (KEEP) and a generalizable populationealth survey (NHANES 1999-2004). Greaterercentages of KEEP participants were at risk ofKD and anemia, including African Americans,ho were 3 times more prevalent in KEEP thanHANES. Risk factors for CKD and CVD5,9,14

lso were better represented in KEEP popula-ions than in NHANES. For example, obesity

able Logistic Regressions: KEEP

I* WHO†

POdds Ratio (95%

confidence interval) P

0.01 1.27 (1.12-1.43) �0.001�0.001 1.48 (1.36-1.60) �0.001

1�0.001 1.17 (1.08-1.26) �0.001�0.001 2.06 (1.86-2.28) �0.001

1�0.001 0.68 (0.64-0.72) �0.001

1�0.001 3.00 (2.81-3.20) �0.001�0.001 1.42 (1.29-1.57) �0.001

1�0.001 0.80 (0.71-0.90) �0.001�0.001 0.62 (0.56-0.69) �0.001�0.001 0.87 (0.80-0.94) �0.001�0.001 1.76 (1.66-1.88) �0.001

0.03 1.07 (1.00-1.14) 0.06�0.001 1.29 (1.21-1.38) �0.001

0.6 1.02 (0.96-1.09) 0.50.09 0.97 (0.90-1.04) 0.40.7 1.00 (0.96-1.06) 0.9

�0.001 1.85 (1.74-1.97) �0.001

10.2 1.15 (0.93-1.43) 0.20.6 0.96 (0.77-1.19) 0.70.02 1.15 (0.93-1.41) 0.20.9 1.03 (0.83-1.26) 0.80.4 1.12 (0.91-1.37) 0.3

gistic regression. For example, analysis of cohort year is

NES, National Health and Nutrition Examination Survey;mes Quality Initiative.en and less than 12 g/dL (�120 g/L) for women.n and less than 12 g/dL (�120 g/L) for women.

ltivari

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5%erval)

31)45)

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as 1.4 times; hypertension was 2 times; and

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McFarlane et alS54

iabetes was 4 times more prevalent in KEEPhan NHANES. Not surprisingly, the KEEP popu-ation had a greater rate of CKD, with an associ-ted much greater prevalence of anemia; thisalue was 2.2 times greater than in the NHANESample population.

The greater prevalence of anemia observed inhe KEEP cohort was consistent across sex, ra-ial and ethnic groups, and CVD risk categories,xcept for smoking. The high prevalence ofiabetes observed in the KEEP cohort, 26.8%ompared with 6.7% in the NHANES sampleopulation, likely is a major contributor to thereater prevalence of anemia in KEEP partici-ants through its effect on risk of CKD and otherechanisms.4 Anemia is common in patientsith diabetes and often goes unrecognized andntreated.17-19 Although eGFR and iron storesre the strongest predictors of hemoglobin levelsn patients with diabetes, these factors do notully account for the increased prevalence ofnemia in the diabetic population.4,19 Other fac-ors, such as absolute and/or relative erythropoi-tin deficiency, inflammation, and oxidativetress, may explain the development of anemia inatients with diabetes and CKD. Furthermore,ccumulating evidence indicates that in patientsith early diabetic nephropathy, anemia is a

ommon finding and associated with erythropoi-tin deficiency.4,17

Although men had greater hemoglobin valueshan women, they also had greater rates of moredvanced CKD. The KDOQI definition with aower threshold for anemia detection in men13.5 g/dL [135 g/L]) thus was more reflective ofhe severity of CKD observed in men, resultingn a 30% greater risk of anemia in men thanomen. This is in contrast to the WHO anemiaefinition, with a lower hemoglobin cutoff valueor men (13.0 g/dL [130 g/L]) or a greater thresh-ld for diagnosing anemia in men, which re-ersed the odds of anemia between sexes; womenad a 32% greater risk of anemia than men usingHO criteria.The greater prevalence of anemia in partici-

ants older than 60 years compared with thoseged 46 to 60 years likely is a reflection of areater rate of CKD in older participants andower eGFRs with aging.20 Conversely, thereater risk of anemia in younger KEEP partici-

ants may represent mechanisms of anemia other i

han CKD, given the lower prevalence and lessevere CKD in younger participants. It also couldeflect higher representation of women and Afri-an Americans, groups with a greater risk ofnemia independent of CKD.12,13

The lower prevalence of anemia in currentmokers in both the KEEP and NHANES popula-ions is consistent with previous data indicatingreater hemoglobin levels in smokers caused byecondary erythrocytosis.21 Cigarette smokingppears to cause a generalized upward shift ofhe hemoglobin distribution curve, thus decreas-ng the utility of hemoglobin levels to detectnemia in smokers.22

Treatment of anemia is by identification ofnderlying cause, which, in patients with CKD,ay be either functional or actual iron deficiencyith or without erythropoietic hormone resis-

ance or deficiency.23 KEEP data include insuffi-ient specific medication data to address anemiareatment in this study.

Findings from our study have potentially sig-ificant public health implications. Early recogni-ion of anemia through a targeted screening pro-ram for populations at high risk of CKD mayecome important for the development of preven-ive and therapeutic strategies. Decreased work-ng capacity, cognitive impairment, angina, andardiorenal anemia syndrome, a triad of worsen-ng anemia, worsening CKD, and worseningongestive heart failure, are potential conse-uences of anemia of CKD.24

ACKNOWLEDGEMENTSIn addition to the authors listed, the Kidney Early Evalua-

ion Program (KEEP) Investigators are Dennis Andress,D, David Calhoun, MD, Bruce Johnson, MD, Claudine T.

urkovitz, MD, MPH, Chamberlain I. Obialo, MD, Lesley. Stevens, MD, and Michael G. Shlipak, MD.The authors thank Shane Nygaard, BA, and Nan Booth,SW, MPH of the Chronic Disease Research Group foranuscript preparation and manuscript editing, respectively.Support: KEEP is a program of the National Kidney

oundation Inc and is supported by Amgen, Abbott, Gen-yme, Ortho Biotech Products LP, and Novartis, with addi-ional support provided by Siemens Medical Solutions Diag-ostics, Lifescan, Suplena, and OceanSpray Cranberries.Financial Disclosure: Dr Vassalotti reports having re-

eived grant support from the Centers for Disease Controlnd Prevention, but has no conflicts of interest with theubject of this article. Dr Collins has received researchupport from Amgen. The other authors have no conflicts of

nterest with the subject matter of this manuscript.

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Anemia in CKD Data From KEEP and NHANES Population S55

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