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Association of Kidney Function With Anemia
The Third National Health and Nutrition Examination Survey (1988-1994)
Brad C. Astor, PhD, MPH;
Paul Muntner, PhD, MHS;
Adeera Levin, MD, FRCPC;
Joseph A. Eustace, MB, MRCPI, MHS;
Josef Coresh, MD, PhD
Arch Intern Med. 2002;162:1401-1408.
ABSTRACT
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Background Kidney failure is known to cause anemia, which is associated with a
higher risk of cardiac failure and mortality. The impact of milder decreases
in kidney function on hemoglobin levels and anemia in the US population, however,
is unknown.
Methods We analyzed a population-based sample of 15419 participants 20 years
and older in the Third National Health and Nutrition Examination Survey, conducted
from 1988 to 1994.
Results Lower kidney function was associated with a lower hemoglobin level and
a higher prevalence and severity of anemia below, but not above, an estimated
glomerular filtration rate (GFR) of 60 mL/min per 1.73 m2. Adjusted
to the age of 60 years, the predicted median hemoglobin level among men (women)
decreased from 14.9 (13.5) g/dL at an estimated GFR of 60 mL/min per 1.73
m2 to 13.8 (12.2) g/dL at an estimated GFR of 30 mL/min per 1.73
m2 and to 12.0 (10.3) g/dL at an estimated GFR of 15 mL/min per
1.73 m2. The prevalence of anemia (hemoglobin level <12 g/dL
in men and <11 g/dL in women) increased from 1% (95% confidence interval,
0.7%-2%) at an estimated GFR of 60 mL/min per 1.73 m2 to 9% (95%
confidence interval, 4%-19%) at an estimated GFR of 30 mL/min per 1.73 m2 and to 33% (95% confidence interval, 11%-67%) at an estimated GFR
of 15 mL/min per 1.73 m2 among men and to 67% (95% confidence interval,
30%-90%) at an estimated GFR of 15 mL/min per 1.73 m2 among women.
An estimated GFR of 15 to 60 mL/min per 1.73 m2 was present in
4% of the entire population and in 17% of the individuals with anemia.
Conclusion Below an estimated GFR of 60 mL/min per 1.73 m2, lower kidney
function is strongly associated with a higher prevalence of anemia among the
US adult population.
INTRODUCTION
THE INCIDENCE and prevalence of kidney failure in the United States
have increased substantially in the past 20 years, with the number of patients
treated for kidney failure with dialysis or transplantation reaching more
than 300 000 by the end of 1997.1 The
number of individuals with mild kidney dysfunction, however, is much larger.
A recent study2 estimated that as many as 5.6
million adults in the United States, representing 3% of the population, have
early renal insufficiency (serum creatinine levels  1.6 mg/dL in men and 1.4
mg/dL in women).
Kidney failure is known to cause anemia, and most patients undergoing
long-term dialysis require treatment with epoetin alfa.3
Anemia is associated with lower exercise tolerance,4
poorer quality of life,5 and left ventricular
growth6 among patients with chronic renal insufficiency
and with left ventricular growth6 and heart
failure7 among patients undergoing dialysis.
A history of cardiac failure and left ventricular hypertrophy (LVH) are strong
predictors of mortality, and are present in approximately 40% and 70% of patients
starting long-term dialysis in the United States, respectively.8-9
This suggests that the harmful effects of anemia develop well before kidney
function deteriorates to the point of requiring long-term dialysis. Recommendations
for hemoglobin levels among patients undergoing long-term dialysis are 11
to 12 g/dL,10 although the optimal level remains
unclear. Most patients starting dialysis in the United States, however, have
lower hemoglobin levels, and less than a quarter receive epoetin alfa before
initiating dialysis.11 Previous studies that
have investigated the relationship between serum creatinine and hemoglobin
levels have used clinic populations5, 12-16
or have included only patients with severe kidney dysfunction.17
The relation between hemoglobin level and kidney function among individuals
in the general population with milder kidney dysfunction, however, is unknown.
Given the high prevalence of early kidney disease and the impact anemia has
on long-term outcomes, it is important to quantify the extent of anemia and
its relation to kidney function in the general population.
This study uses data from the Third National Health and Nutrition Examination
Survey (NHANES III) to assess the association of kidney function and hemoglobin
levels across the range of kidney function among noninstitutionalized adults
in the United States.
PARTICIPANTS AND METHODS
This study uses data on 15 625 participants 20 years and older
who participated in NHANES III. This survey was conducted from 1988 to 1994
by the National Center for Health Statistics, Centers for Disease Control
and Prevention, Hyattsville, Md. NHANES III uses a complex, multistage, clustering
sampling design, and provides cross-sectional nationally representative data
on the health and nutritional status of the civilian noninstitutionalized
US population.18-19 Non-Hispanic
black persons, Mexican Americans, elderly persons, and children were deliberately
oversampled in this survey, allowing the calculation of more precise estimates
of the distribution of variables in these groups.
Standardized questionnaires were administered in the home, followed
by a detailed physical examination and serum collection at a mobile examination
center. Race was self-selected and categorized as non-Hispanic white, non-Hispanic
black, Mexican American, or other. Participants were considered to have diabetes
mellitus if they reported ever having been told by a physician that they had
diabetes or "sugar diabetes" at a time other than during pregnancy or if they
were taking insulin or a "diabetes pill" at the time of the questionnaire.
The hemoglobin level was measured using an automated hematology analyzer
(Coulter S-Plus JR; Beckman Coulter, Inc, Fullerton, Calif). Anemia was defined
using World Health Organization criteria (hemoglobin level <13 g/dL for
men and <12 g/dL for women) for some analyses.20
To focus on clinically significant and potentially treatable anemia, however,
we used a more stringent definition (hemoglobin level <12 g/dL for men
and <11 g/dL for women) for most analyses. The serum ferritin level was
measured by an immunoradiometric assay (Bio-Rad Laboratories, Hercules, Calif).
A low serum ferritin level was defined as less than 10 ng/mL. Transferrin
saturation was calculated as follows: 100 x (serum iron level ÷
total iron binding capacity); this was measured by a colorimetric method (Alpkem
RFA 300 analyzer; Alpkem, Inc, Clackamas, Ore). Low transferrin saturation
was defined as less than 15%. Iron status was categorized as functional deficiency
if a participant had low transferrin saturation but a normal serum ferritin
level and as absolute iron deficiency if a participant had a low serum ferritin
level. The C-reactive protein (CRP) level was measured by latex-enhanced nephelometry
(Behring Diagnostics, Inc, Somerville, NJ). An elevated CRP level was defined
as 1.0 mg/dL or greater.
Creatinine measurements were performed at the White Sands Research Center
laboratory, Alamogordo, NM, by the modified kinetic Jaffe reaction21 using an autoanalyzer (Hitachi 737; Boehringer Mannheim
Corporation, Indianapolis, Ind), and were reported using conventional units
(1 mg/dL = 88.4 µmol/L). The coefficient of variation for creatinine
determination was 2.7% at 1.7 mg/dL, 2.1% at 3.5 mg/dL, and 2.0% at 4.4 mg/dL
during the study, with stable quality control.18
Data on physiologic variation in creatinine level were obtained in a sample
of 1921 participants who underwent a second creatinine measurement. The mean
percentage difference between the 2 measurements, collected a mean of 17 days
apart, was 0.2% (SD, 9.7%).2 The assay had
stable quality control measures during the study. A review of College of American
Pathologists Survey data indicated that the laboratory mean for serum creatinine
level from 1992 to 1994 was within acceptable limits, but higher than the
mean of all laboratories surveyed. The glomerular filtration rate (GFR) was
estimated using the abbreviated equation developed at The Cleveland Clinic
laboratory, Cleveland, Ohio, for the Modification of Diet in Renal Disease
Study as follows: estimated GFR = 186.3 x (serum creatinine level-1.154) x (age-0.203) x (0.742 if
female) x (1.21 if black).22 Serum creatinine
measurements were recalibrated to results obtained at The Cleveland Clinic
during the Modification of Diet in Renal Disease Study based on reanalysis
of frozen samples (342 from NHANES III and 212 from the Modification of Diet
in Renal Disease Study) at both laboratories during 1999. Individuals with
a physiologically implausibly high estimated GFR were assigned a maximum of
200 mL/min per 1.73 m2 (0.3% of the men and 1.2% of the women).
Prevalence estimates were calculated based on sampling weights provided
by the National Center for Health Statistics. These weights account for the
differential probability of selection and nonresponse and allow estimation
of prevalence in the civilian noninstitutionalized US population. The sampling
weights were adjusted by the proportion of participants missing creatinine
data in each age, sex, and race design stratum. This corrects differences
in missing data across sampling strata, but assumes that data within strata
are missing randomly. Analyses were conducted using statistical software (Stata
svy commands) for analyzing complex survey design data, with 49 strata and
98 primary sampling units.23 These commands
implement similar algorithms to other statistical software (SUDAAN; Research
Triangle Institute, Research Triangle Park, NC).24
A total of 15444 of 15625 participants 20 years and older who were examined
had serum creatinine and hemoglobin levels available for analysis. The proportion
of participants with missing data was lower among non-Hispanic black persons,
Mexican Americans, and other races than among non-Hispanic white persons.
The participants with missing data were similar to those without missing data
for age and sex.
The estimated GFR was analyzed as a continuous measure and divided into
4 categories (15-29, 30-59, 60-89, and 90 mL/min per 1.73 m2).
Patients with an estimated GFR below 15 mL/min per 1.73 m2 (n =
25) were excluded from all analyses. Quantile regression models, including
fifth-order polynomials of estimated GFR and age, were used to determine the
association of estimated GFR and the 5th, 50th, and 95th percentiles of hemoglobin
level.25-26 These models used
the survey weights but could not incorporate the clustered sampling design.
The figures generated include data from all participants, although data are
only presented for a limited range of estimated GFR. To detect a separate
association between estimated GFR and hemoglobin level above an estimated
GFR of 90 mL/min per 1.73 m2, this association was also modeled
using linear splines.27 The association of
estimated GFR with the prevalence of anemia was investigated using logistic
regression models with fifth-order polynomials of estimated GFR and age. These
models were performed for men and women separately, and adjusted to the age
of 60 years. The results of these models were used to predict the prevalence
of anemia among participants aged 60 years across the range of estimated GFR.
Independent predictors of anemia were identified in sex-specific multivariate
logistic regression models. All variables were included in the multivariate
models, except elevated CRP level, which may be in the causal pathway between
reduced kidney function and anemia. Dummy variables were used in place of
missing values for independent variables other than age, race, sex, and estimated
GFR (<1% of individuals). Separate multivariate models, including data
from both sexes, were developed to test the interaction of sex with the association
between estimated GFR and other variables. These analyses were performed again,
excluding participants with functional or absolute iron deficiency or an elevated
CRP level.
RESULTS
STUDY POPULATION
Table 1 shows the number
of survey participants by demographic and clinical characteristics and the
estimated distribution of individuals, the mean hemoglobin level, and the
prevalence of anemia among the civilian noninstitutionalized US population
20 years or older. The overall mean hemoglobin level was 14.1 g/dL, and the
overall prevalence of anemia, defined as a hemoglobin level less than 12 g/dL
among men and less than 11 g/dL among women, was 1.9% (1.1% among men and
2.5% among women). The prevalence of World Health Organization–defined
anemia (hemoglobin level <13 g/dL among men and <12 g/dL among women)
was 7.3% (3.5% among men and 10.7% among women). An estimated GFR below 60
mL/min per 1.73 m2 was strongly associated with lower hemoglobin
levels and a higher prevalence of anemia. The prevalence of anemia was 1.8%
among those with an estimated GFR of 90 mL/min per 1.73 m2 or higher,
compared with 5.2% among those with an estimated GFR between 30 and 59 mL/min
per 1.73 m2 and 44.1% among those with an estimated GFR between
15 and 29 mL/min per 1.73 m2. Non-Hispanic black persons had a
lower mean hemoglobin level than non-Hispanic white persons. Older age, female
sex, and elevated CRP level were also significantly associated with lower
hemoglobin levels. The distribution of hemoglobin level by sex is shown in Figure 1. Among those participants with complete
information on iron stores (15 332 [99%]), 14% had transferrin saturation
below 15% and 4% had a serum ferritin level below 10 ng/mL. Iron status was
categorized as normal in 85% of the participants, functional iron deficiency
in 12%, and absolute iron deficiency in 4% (percentages do not total 100 because
of rounding). The mean hemoglobin level was significantly lower among participants
with functional (13.4 g/dL) and absolute (12.0 g/dL) iron deficiency compared
with those with a normal iron status (14.3 g/dL) (P<.001
for trend).
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Table 1. Hemoglobin Level and Prevalence of Anemia by Demographic and
Clinical Characteristics: NHANES III (1988-1994)*
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Figure 1. Distribution of hemoglobin levels
among men and women 20 years and older who participated in the Third National
Health and Nutrition Examination Survey (1988-1994).
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ASSOCIATION OF KIDNEY FUNCTION WITH HEMOGLOBIN LEVELS
Figure 2A and B shows the
median and 5th and 95th percentiles of hemoglobin levels across a range of
estimated GFRs for men and women, respectively, adjusted to the age of 60
years. Below 60 mL/min per 1.73 m2, a lower estimated GFR was associated
with a lower hemoglobin level for men and women. The median hemoglobin level
among men decreased from 14.9 g/dL at an estimated GFR of 60 mL/min per 1.73
m2 to 13.8 g/dL at an estimated GFR of 30 mL/min per 1.73 m2 and to 12.0 g/dL at an estimated GFR of 15 mL/min per 1.73 m2. The median hemoglobin level among women similarly decreased from
13.5 g/dL at an estimated GFR of 60 mL/min per 1.73 m2 to 12.2
g/dL at an estimated GFR of 30 mL/min per 1.73 m2 and to 10.3 g/dL
at an estimated GFR of 15 mL/min per 1.73 m2. Above an estimated
GFR of 90 mL/min per 1.73 m2, the median hemoglobin level was mildly
but significantly (P<.001) lower at higher estimated
GFRs. Similar results were obtained in analyses excluding individuals with
functional or absolute iron deficiency or an elevated CRP level.
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Figure 2. Median and 5th and 95th percentiles
of hemoglobin levels among men (A) and women (B) 20 years and older who participated
in the Third National Health and Nutrition Examination Survey (1988-1994).
All values are adjusted to the age of 60 years. Estimates and 95% confidence
intervals are demarcated at selected levels of estimated glomerular filtration
rate (GFR). Marks near the abscissa indicate the estimated GFRs of individual
data points.
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ASSOCIATION OF KIDNEY FUNCTION WITH PREVALENCE OF ANEMIA
The prevalence of anemia by estimated GFR category and race is shown
in Table 2. A lower estimated
GFR was associated with a higher prevalence of anemia in non-Hispanic white
persons (P<.001), non-Hispanic black persons (P<.001), and Mexican Americans (P<.02). Non-Hispanic black participants were much more likely than
their non-Hispanic white counterparts to have anemia at each estimated GFR
category (P<.02 for all). Applying the population-based
weights of NHANES III allows us to make national estimates. The 44.1% overall
prevalence of anemia at an estimated GFR of 15 to 29 mL/min per 1.73 m2corresponds to approximately 160 000 (SE, 44000) noninstitutionalized
civilians in the United States in 1991. The 5.2% overall prevalence of anemia
at an estimated GFR of 30 to 59 mL/min per 1.73 m2 corresponds
to approximately 390 000 (SE, 54 000) noninstitutionalized civilians
in the United States in 1991. These totals represent an estimated 4.9% and
12.0%, respectively, of the estimated total number of cases of anemia among
adults in the noninstitutionalized US population.
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Table 2. Prevalence of Anemia by Estimated Glomerular Filtration Rate
and Race: NHANES III (1988-1994)*
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Figure 3A and B shows the
prevalence of hemoglobin levels below 11, 12, and 13 g/dL, for men and women,
respectively, adjusted to the age of 60 years. The prevalence of a low hemoglobin
level, defined at each cut point, was substantially higher at estimated GFRs
below 60 mL/min per 1.73 m2. At an estimated GFR of 60 mL/min per
1.73 m2, approximately 1% of men had a hemoglobin level below 12
g/dL and 1% of women had a hemoglobin level below 11 g/dL. At an estimated
GFR of 30 mL/min per 1.73 m2, both were increased to approximately
9%. At an estimated GFR of 15 mL/min per 1.73 m2, 33% (95% confidence
interval, 11%-67%) of men had a hemoglobin level of less than 12 g/dL and
67% (95% confidence interval, 30%-90%) of women had a hemoglobin level of
less than 11 g/dL. Similar results were obtained among individuals without
functional or absolute iron deficiency or an elevated CRP level.
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Figure 3. Predicted prevalence of hemoglobin
level less than 11, less than 12, and less than 13 g/dL among men (A) and
women (B) 20 years and older who participated in the Third National Health
and Nutrition Examination Survey (1988-1994). All values are adjusted to the
age of 60 years. Estimates and 95% confidence intervals are demarcated at
selected levels of estimated glomerular filtration rate (GFR).
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INDEPENDENT PREDICTORS OF ANEMIA
Table 3 shows adjusted odds
ratios of anemia associated with demographic and clinical factors for men
and women separately. After adjustment for all other variables in the table,
a lower estimated GFR was associated with a higher prevalence of anemia in
men and women (P<.001 for trend). Non-Hispanic
black race was strongly associated with the prevalence of anemia among men
and women. Older age was significantly associated with the prevalence of anemia
among men but not women (P<.001 for the interaction),
whereas Mexican American race was significantly associated with a higher prevalence
of anemia among women but not men (P<.001 for
the interaction). There was no significant interaction between sex (P = .39) or race (P = .64) and
the association of estimated GFR with anemia. Functional and absolute iron
deficiency remained significantly associated (P<.001)
with anemia in men and women after adjustment. Similar associations between
estimated GFR and the prevalence of anemia were obtained among individuals
without iron deficiency or an elevated CRP level and after adjustment for
an elevated CRP level.
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Table 3. Adjusted Odds Ratios of Anemia by Sex: NHANES III (1988-1994)*
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COMMENT
The results of this study show that moderate and severe kidney dysfunction
are associated with a lower hemoglobin level and a higher prevalence of anemia
below an estimated GFR of 60 mL/min per 1.73 m2. The age-adjusted
median, and the 5th and 95th percentiles, of the hemoglobin level were lower
at lower estimated GFRs for men and women. The associations were similar across
ethnic groups, but the prevalence of anemia was much higher among non-Hispanic
black and Mexican American participants than among non-Hispanic white participants.
This study used a large, nationally representative, stratified sample,
which allows estimation of the prevalence of anemia across all levels of kidney
function for the noninstitutionalized civilian US population. The prevalence
of anemia was 1.8% at an estimated GFR above 90 mL/min per 1.73 m2,
compared with 5.2% at an estimated GFR of 30 to 59 mL/min per 1.73 m2 and 44.1% at an estimated GFR of 15 to 29 mL/min per 1.73 m2. These estimates correspond to approximately 387 400 individuals
with an estimated GFR of 30 to 59 mL/min per 1.73 m2 (12% of adults
with anemia) and approximately 160 000 individuals with an estimated
GFR of 15 to 29 mL/min per 1.73 m2 (5% of adults with anemia).
Adjusted to the age of 60 years, the prevalence of anemia increased from 1%
to 9% as the estimated GFR declined from 60 to 30 mL/min per 1.73 m2. Below an estimated GFR of 30 mL/min per 1.73 m2, precision
was limited, but the increase was steep, with an estimated 33% of men and
67% of women having anemia at an estimated GFR of 15 mL/min per 1.73 m2. We also found a wide distribution of hemoglobin levels at each level
of kidney function. To our knowledge, these are the first data available in
the general population that show the association of hemoglobin level with
GFR across the entire range of kidney function.
Previous studies have reported a significant correlation between severity
of anemia and various measures of kidney function among clinic populations5, 12-16
or among individuals in the general population with serum creatinine levels
above 2.0 mg/dL.17 Most of these studies12-15 have
used hematocrit, rather than hemoglobin level, to define anemia. This study
focuses on hemoglobin level because it can be measured directly and is a more
precise measure of erythropoiesis than is hematocrit, a derived value that
can be affected by plasma water.10 A report
from the Canadian Multicentre Study in Early Renal Disease found a mean hemoglobin
level of 14.3 g/dL among 88 patients referred to a nephrology clinic with
a creatinine clearance greater than 50 mL/min, compared with 12.8 g/dL among
226 patients with a creatinine clearance of 25 to 50 mL/min and 11.7 g/dL
among 133 patients with a lower creatinine clearance (P<.001).5 A recent large study16 in the United States reported similar estimates.
These results are consistent with the estimates for the general US population
in the present study.
Anemia is associated with many negative consequences among patients
with kidney dysfunction, including lower exercise tolerance and quality of
life, LVH, and congestive heart failure.4, 28-30
Among patients starting renal replacement therapy, approximately two thirds
have LVH and half have a history of cardiac failure.31-32
These data suggest that the harmful effects of anemia are evident before the
onset of kidney failure. The results of the present study confirm the presence
of anemia among individuals with moderate kidney dysfunction, and provide
population-based estimates of the association between kidney function and
hemoglobin levels. Using these same data, we estimate that 8.0 million individuals
have moderate kidney dysfunction (estimated GFR <60 mL/min per 1.73 m2). The incidence and prevalence of kidney failure continues to grow
in the United States.1 Presumably, the number
of individuals in the United States with moderate kidney dysfunction is also
increasing. Thus, the potential burden of anemia, and its associated complications
in this population, is large and may be increasing.
Anemia among patients with kidney failure or severe kidney dysfunction
is treated effectively with recombinant human epoetin alfa. Correction of
anemia with epoetin alfa improves exercise capacity and quality of life4, 33 and decreases morbidity and hospitalizations34 among patients undergoing long-term dialysis. Randomized
controlled trials suggest that normalization of the hemoglobin level prevents
left ventricular dilation in patients with severe kidney dysfunction without
symptomatic cardiac disease,35 but may not
be beneficial in patients with symptomatic disease36
or severe left ventricular dilation.35 The
correction of anemia also prevented progression and reversed LVH in 2 small
studies37-38 of patients with
renal insufficiency, although this has yet to be confirmed in controlled studies.
Although the anemia associated with chronic kidney disease may be modifiable,
most patients reaching kidney failure do not have acceptable levels of hemoglobin
at the initiation of dialysis. The optimal hemoglobin level is uncertain,
but recommendations are 11 to 12 g/dL.10 Obrador
et al11 found that more than half of the patients
starting dialysis in the United States from 1995 to 1997 had a hematocrit
of less than 28% and less than a quarter had received epoetin alfa before
starting dialysis. This highlights the need for increased detection and appropriate
management of anemia among patients being followed up for chronic kidney disease.
Timely referral to a nephrologist may be one important factor in the suboptimal
treatment of anemia in these patients. Published studies39
have found consistently higher hemoglobin levels among patients referred to
a nephrologist at least 4 months before the initiation of dialysis than among
patients referred later.
The prevalence of anemia was much higher in non-Hispanic black men and
women than in non-Hispanic white participants. This was true before and after
adjustment for the estimated GFR. The high prevalence of anemia among non-Hispanic
black participants with a moderately decreased GFR may be important in explaining
the higher prevalence of LVH among black persons.40
The prevalence of sickle cell anemia among black persons (<0.3%) cannot
explain most of the elevated prevalence of anemia in this group.41
Mexican American women also had a higher prevalence of anemia than did their
non-Hispanic white counterparts. This finding deserves further investigation.
Iron deficiency was a strong predictor of anemia in this study. Many
patients with kidney disease and anemia have iron deficiency and benefit from
iron supplementation,42 and most patients receiving
epoetin alfa require iron supplementation to achieve adequate hemoglobin levels.43 The relation between kidney function and hemoglobin
level in this study, however, was unchanged in analyses that excluded participants
with a low serum ferritin level or a low transferrin saturation.
This study is limited by its cross-sectional design. Prospective data
are needed to estimate expected declines in hemoglobin level as kidney disease
progresses in an individual. Another limitation of this study is that despite
the large size of the NHANES III population, there were relatively few (n
= 52) participants with an estimated GFR of 15 to 29 mL/min per 1.73 m2. It is possible that response rates were lower at the lower levels
of GFR, at which individuals are more likely to be symptomatic. A similar
bias may have occurred at lower hemoglobin levels, which are associated with
increased fatigue. Therefore, the observed associations may underestimate
the association at low GFRs. Estimating the GFR based on serum creatinine
level and other characteristics has a long history.44
The equation we used is relatively new, but was developed on a large and systematically
collected data set.22 The precision of estimated
GFR increases with decreasing GFR, giving us more confidence in the observed
association at an estimated GFR of 60 mL/min per 1.73 m2 and below.
Within the normal GFR range of 90 mL/min per 1.73 m2 or greater,
the relative importance of nonrenal determinants on the estimated GFR increases.
High estimates of GFR correspond to low serum creatinine levels, which can
be the result of low muscle mass or a diet low in meat intake. Low muscle
mass may in turn be related to a higher prevalence of chronic disease and
anemia. This may partially explain the observed association of high estimated
GFR and lower hemoglobin level. Several studies have demonstrated that an
elevated serum creatinine level and a reduced GFR are relatively insensitive,
but highly specific, indicators of chronic kidney disease. This results from
the insensitivity of serum creatinine level in detecting a decline in GFR
and from compensatory mechanisms that serve to maintain a normal GFR despite
a reduction in functional renal mass.45 The
associations observed in this study, therefore, may underestimate the true
relation between declining kidney function and anemia.
In summary, this study provides a description of the association between
kidney function and hemoglobin level across the entire range of kidney function
in the US population. The results demonstrate that participants with an estimated
GFR below 60 mL/min per 1.73 m2are much more likely to have anemia,
and that the prevalence and severity of anemia increase with declining kidney
function. Because the population with moderate kidney dysfunction in the United
States is large, the burden of disease associated with anemia in this population
may be considerable.
AUTHOR INFORMATION
Accepted for publication October 15, 2001.
This study was supported in part by a grant from the National Kidney
Foundation, New York, NY, as part of the Kidney Disease Outcome Quality Initiative;
by grant T32HL07024-23 from the National Heart, Lung, and Blood Institute,
Bethesda, Md (Dr Astor); by The Johns Hopkins University Clinical Scientist
Career Development Award (Dr Eustace); in part by grants RR00722 and RR00035
from the National Center for Research Resources, Bethesda (Dr Coresh); and
by an American Heart Association Established Investigator Award (Dr Coresh).
This study was presented in abstract form at the 34th annual meeting
of the American Society of Nephrology, San Francisco, Calif, October 15, 2001.
Corresponding author and reprints: Brad C. Astor, PhD, MPH, Welch
Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins
University, 2024 E Monument St, Suite 2-500, Baltimore, MD 21205 (e-mail: bastor{at}jhsph.edu).
From the Departments of Epidemiology (Drs Astor and Coresh) and Biostatistics
(Dr Coresh), The Johns Hopkins Bloomberg School of Public Health, Baltimore,
Md; the Welch Center for Prevention, Epidemiology, and Clinical Research,
The Johns Hopkins University, Baltimore (Drs Astor and Coresh); the Department
of Epidemiology, Tulane School of Public Health and Tropical Medicine, New
Orleans, La (Dr Muntner); the Division of Nephrology, Department of Medicine,
St Paul's Hospital, University of British Columbia, Vancouver (Dr Levin);
and the Department of Medicine, The Johns Hopkins University School of Medicine,
Baltimore (Drs Eustace and Coresh). Dr Levin is an advisor/consultant to Amgen,
Inc, Ortho Biotech Inc, Janssen-Cilag, and F. Hoffmann-La Roche in North America
and internationally. She is involved in studies with Ortho Biotech Inc and
Amgen, Inc, and has received honoraria for presentations. These companies
have no affiliation with this article, and they have not influenced the article
in any way.
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