8. Epidemiology of Chronic Kidney Disease and Anemia-Robinson

8/12/2019 8. Epidemiology of Chronic Kidney Disease and Anemia-Robinson

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Epidemiology of Chronic Kidney Diseaseand Anemia

Bruce E. Robinson, MD, MPH

Anemia is a common comorbidity of chronic kidney

disease (CKD). As the diseased kidney loses its ability toproduce the erythropoietin essential to the produc-tion of hemoglobin, anemia ensues. The age-relatedrise in CKD makes anemia in CKD a problem of increas-ing prevalence among residents of long-term care fa-cilities. CKD refers to the entire continuum of renaldisease that progresses from mildly impaired kidneyfunction (stage 1, glomerular filtration rate [GFR]90mL/min/1.73 m2) to significant deterioration, requiringdialysis or kidney transplant in what is categorized asstage 5 (GFR 15 mL/min/1.73 m2). The definition ofanemia is controversial. The WHO defines anemia as

hemoglobin 13 g/dL for men and 12 g/dL for

women. The National Kidney Foundations Kidney Dis-ease Outcomes Quality Initiative, which is the criteriaused for Medicare reimbursement, defines anemia inadult men and postmenopausal women as hemoglo-bin12 g/dL, or11 g/dL in a premenopausal woman.(J Am Med Dir Assoc 2006; 7: S3S6)

Keywords: Prevalence; chronic kidney disease (CKD);anemia; glomerular filtration rate (GFR); Modificationof Diet in Renal Disease (MDRD) formula; Cockcroft-Gault formula

INTRODUCTION

Epidemiologic studies have documented a dramatic age-related rise in the prevalence of chronic kidney disease

(CKD) and anemia.1,2 These 2 common chronic conditionsare associated with increases in mortality and morbidity, func-

tional decline, hospitalizations, and increased health carecosts.

Chronic Kidney Disease

The incidence and prevalence of kidney disease worldwideand in the United States has risen markedly in the past

decade.3 About 20 million Americans from 1988 to 1994 orapproximately 11% of all US adultsare living with CKD

(stages 15), and the incidence and prevalence of kidneydisease are increasing.4

As the numbers have grown over the last few years, thenomenclature of CKD has evolved. In 2001, the National

Kidney Foundation (NKF) issued a consensus statement rec-ommending CKD as the preferred label and glomerular filtra-

tion rate (GFR) as the diagnostic test of choice.5

CKD refers to the entire continuum of renal disease that

progresses from renal abnormality with normal GFR (stage 1)through mild CKD (stage 2, GFR 6090 mL/min/1.73 m2)

through moderate CKD (stage 3, GFR 3060 mL/min/1.73

m2) to significant deterioration requiring dialysis or kidney

transplant in stage 5 (GFR 15 mL/min/1.73 m2). End-stage

renal disease is an administrative term that indicates that apatient is being treated with dialysis or kidney transplant.

Traditionally, CKD in nursing home residents has onlybeen thought of as those in stages 4 and 5. In fact, most people

with CKD are asymptomatic. Stage 1 CKD is typically notdetected and requires some other information, for example,

the presence of proteinuria or hematuria, to bring it to theclinicians attention.

Epidemiologically, a major observation of the last few yearshas been the recognition of the very large number of people

who have GFR between 30 and 59 mL/min/1.73 m2, placing

them at stage 3 CKD. They represent the bulk of patients whosuffer most of the consequences of CKD in the United States.

While approximately 400,000 patients in the United Stateshave stage 4 (severe) CKD and about 300,000 are on dialysis,

the majority of CKD patients (7.6 million) are in stage 3(Figure 1).6

Significance of declining GFR with age

Why worry about the GFR in elders? At maturity, theaverage GFR is 120 mL/min/1.73 m2. As the years go by,

adults lose about 1 mL/min/y. An 85-year-old person, then,can be expected to have a GFR just under 60 mL/min/1.73

m2qualifying that person as having stage 3 CKD. One canargue that, on average, CKD is to be expected in older people

who are not free of disease.Data from longitudinal studies in the last 20 years has

demonstrated the phenomenon of successful aging. That is,even though usual aging means a progressive decline in GFR,

that decline is not universal. A substantial number of peoplemanage to go into late life with very good GFR and have no

CKD. Those who develop even modest CKD, however, tendto experience cardiovascular morbidity and mortality above

Florida State University College of Medicine, University of South Florida Col-

lege of Medicine, Sarasota, FL.

Address correspondence to Bruce E. Robinson, MD, MPH, University of South

Florida College of Medicine, 1700 S. TamiamiTrail, Sarasota, FL 34239. E-mail:

[email protected]

Copyright 2006 American Medical Directors Association

DOI: 10.1016/j.jamda.2006.09.004

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the norm. Decreased GFR is associated with complications invirtually all organ systems. Frequency and severity of compli-

cations worsen as GFR declines. Complications associatedwith CKD include high blood pressure, anemia, malnutrition,

bone disease, and decreased overall physical functioning. Twomajor community studies (National Health and Nutrition

Examination Survey [NHANES III] and the NKFs KidneyEarly Evaluation Program [KEEP]) have documented that the

prevalence of CKD rises with increasing age (Figure 2).The NHANES III was a large epidemiologic study per-

formed to evaluate the health and nutrition of the US pop-

ulation. The NHANES III data demonstrate that CKD in-creases in individuals older than 60 years of age, and that the

percentage of patients with CKD increases as one approaches75 years of age.6

The KEEP is an ongoing community-based health-screen-ing program that focuses on people at high risk for developing

CKD. In the program, sponsored by the NKF, individuals areevaluated for CKD if they have a personal health history of

hypertension or diabetes or have a family history of diabetes,hypertension, or CKD. Thisclinical population has a much

higher prevalence of CKD.7,8

To determine the extent of renal insufficiency among in-

stitutionalized elders, a group at risk based on age and frailhealth, Garg and colleagues1 carried out a large retrospective

cross-sectional study of 9931 residents aged 65 years and older

in 87 Canadian nursing homes. The Garg study, which rep-resents the first published report of CKD among long-term

care patients based on GFR, estimated that nearly 40% of theresidents had CKD (defined as GFR 60 mL/min/1.73 m2

using the modified Modification of Diet in Renal Disease[MDRD] Study Group equation).1 The mean age in the Garg

study was 82 years for men and 85 years for women. This studyshowed how common CKD is in this nursing home popula-

tion (Figure 3). Gargs group documented that about 30% ofthe oldest men and women in a nursing home population had

CKD at stage 3 or higher.Gargs team also compared 2 commonly used methods for

estimating GFR: the Cockcroft-Gault and MDRD formulas.Gargs group concluded that both equations may underesti-

mate the gold-standard GFR in these elderly patients, withthe underestimation beinggreater with the Cockcroft-Gault

than the MDRD formula.1 Although both the Cockcroft-Gault and the MDRD formulas have been used in the elderly

population, neither has been validated in the elderly(Table 1).1,913

Ania and colleagues14 were among the first to documentthat the prevalence of anemia in older adults rises with age.

Fig. 1. Epidemiologically, a major observation of the last few years

has been the recognition of the very large number of people who

have GFR between 30 and 59 mL/min/1.73 m2, placing them at

stage 3 CKD. While approximately 400,000 patients in the United

States have stage 4 (severe) CKD and about 300,000 are on dialysis,

the majority of CKD patients (7.6 million) are in stage 3.6

Fig. 2. In both the NHANES and KEEP studies, the prevalence ofCKD, defined as a serum creatinine level1.3 mg/dL in women and

1.5 mg/dL in men, rose rapidly in those aged 60 years and over.

Reprinted with permission from American Journal of Kidney Dis-

ease.7 Copyright 2005, National Kidney Foundation.

Fig. 3. The Garg study estimated that 30% of the oldest residents

had stage 3 or higher CKD. Reprinted with permission from Kidney

International.1 Copyright 2004, Nature Publishing Group.

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Anias group from the Mayo Clinic in Rochester, MN, eval-

uated 618 men and women aged 65 years or older in a

Minnesota county. All elders were diagnosed with anemiausing the World Health Organization (WHO) definition ofhemoglobin of13 g/dL for men and 12 g/dL for women.

The group evaluated the cohort from 1986 until death or lossof clinical contact through 1994. The corrected annual inci-

dence of anemia rose with age in this population-based study,with rates higher in men (90.3 per 1000; 95% confidence

interval [CI], 79.2101.4) than women (69.1 per 1000; 95%CI, 62.375.8) (Figure 4).14 In 465 cases (75%), anemia was

detected in conjunction with a hospitalization, but admissionwas owing to anemia in only 57 instances. Half of the cases

were caused by blood loss, two thirds of these as a result of

surgery. The cause of anemia was uncertain in 102 cases(16%). One third of the patients were transfused with a

median of 3 units. Overall survival was worse than expected,

but was better among those with anemia caused by blood loss.

Mortality attributable to malignancy, mental disorders, circu-latory and respiratory diseases, ill-defined conditions, and in-juries was significantly increased among these older patients

with anemia.15

An analysis of data from NHANES III revealed that one

third of the anemia in people aged 65 and older was due to anutritional deficiency; one third was nonnutritional anemia

that could not be explained, and one third was caused byeither renal insufficiency or chronic inflammation.16

Anemia in the Nursing Home

In 2004, Andrew Artz and colleagues2 reported their in-

vestigation of the prevalence of anemia in chronically illnursing home residents. In a multicenter study of 900 resi-

dents who had a mean age of 79 years and a median age of 82years, Artzs team documented that the 6-month prevalence

of anemiadefined using the WHO values of13 g/dL formen and 12 g/dL for womenwas 48%. Any residents in

whom anemia was discovered at any point in the 6 monthsprior to chart review were considered positive for anemia.

The 6-month hospitalization rate among patients with ane-

mia was 30%, compared with 15.8% of those without anemia.What therapy was offered for the anemia? Among the 704

residents who had charts with reliably available dates, 2.3%

had received a red cell transfusion. Among the 816 residentswith documentation regarding use of recombinant humanerythropoietin, 3% received this therapy. The researchers

concluded, It is apparent that anemia is common in nursinghomes, but directed therapy is not.2

Anemia and Chronic Kidney Disease

Anemia is a common comorbidity of CKD. As the diseased

kidney loses its ability to produce the erythropoietin essentialto the production of hemoglobin, anemiaensues.5 In a study

of 60 nursing home residents, Artz et al17 found that 10% ofpatients had both anemia and CKD. Anemia of chronic

Fig. 4. Anias group was among the first to document that the

prevalence of anemia in older adults is high and rises with age.

Reprinted with permission from Mayo Clinic Proceedings.14 Copy-

right 1994, Mayo Foundation for Medical Education and Research.

Table 1. MDRD Versus Cockcroft-Gault in Older Adults

Study N Age (y) Population Results in Older Adults

Cirillo et al.9 380 1888 Mix of age and BMI, as well asrenal/nonrenal disease, andno disease

CG underestimatedGFR more thanMDRD

Fehrman-Ekholm et al.10 52 82.3 Generally healthy patients;67.7 mL/min/1.73 m2

MDRD had strongestcorrelation withactual GFR

Garg et al.1 9931 Men 82 Women 85 Long-term care residents; mixof renal/nonrenal disease

CG underestimates GFRmore than MDRD

Lamb et al.11 52 79.7 CKD; mean GFR 53.3 mL/min/ 1.73 m2

CG had fewermisclassificationsthan MDRD (10 vs 14)

Pedone et al.12 7747 77.8 Admissions to acute care ward(65 y)


Verhave et al.13 134 71.3 Mix of age and BMI, mostlyhypertensive; mean GFR79.4 mL/min/1.73 m2


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diseasewas found in 13% of patients and idiopathic anemia,

in 23%.17 Epidemiologic data from NHANES III and KEEPshow an increase in prevalence of anemia (hemoglobin 12

g/dL) in those aged 61 years and older in the presence of stage3 CKD or higher (GFR 60 mL/min/1.73 m2). More than

half of those older than 75 years with stage 3 or higher CKDhave anemia as well.

Why Care About Anemia?

While low hemoglobin is common in seniors, there is agrowing body of evidence for moving away from a normativedefinition of anemia. The normative criteria developed in

younger adults may not apply to older persons. The findingthat anemia rises more dramatically in men than in women

may be primarily related to the sex difference in how anemiais definedwhich has less relevance in older men than

younger men. As men age and androgen levels decline, oldermen lose the hemoglobin advantage attributable to this sex-

related hormone. Also, older women lose the hemoglobindisadvantage related to iron loss through their menstrual

periods. Because of these age-related changes, defining anemia

below 12 g/dL in women and at the higher level of below 13g/dL in men may not appropriately reflect the biologicalconcept of what is normal for older adults.

Anemia is an important predictor of morbidity and mor-tality in older adults, with evidence for effects on a variety of

clinically important events. The increased mortality associ-ated with anemia in older persons has been shown in a

number of studies.1820 The study by Culleton et al20 foundoptimal mortality and morbidity in hemoglobin ranges of 130

to 150 g/L for women and 140 to 170 g/L for men. Anemia isalso associated with diminished quality of life and physical

function in older adults.2123 The lower the hemoglobin, the

more serious the problem with increased hospitalization rates,mortality, morbidity, and serious adverse consequences topatients.

CONCLUSIONS

CKD stage 3 or greater may affect nearly 43% of residents

in long-term care facilities. Anemia, by the WHO definition,affects nearly 60%. An association has been documented

between anemia and CKD in long-term care residents, and it

is prominent. Further work defining this association will helpdetermine the size of the population that might be targeted for

correction of anemia by erythropoiesis-stimulating proteintreatment. This work is under way using a population of 6000

nursing home residents of a large national chain and willdetermine the prevalence of anemia, CKD, and the associa-

tion between these 2 common chronic conditions.

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8. Epidemiology of Chronic Kidney Disease and Anemia-Robinson