Socioeconomic Factors and Racial Disparities in Kidney Disease Outcomes

Socioeconomic Factors and Racial Disparities in Kidney Disease Outcomes Deidra C. Crews, MD, ScM,*,† Teresa Pfaff, BSN, RN,†,‡ and Neil R. Powe, MD, MPH, MBA§

Summary: African Americans suffer disproportionately from advanced and progressive chronic kidney disease (CKD). Socioeconomic factors are believed to play an important role in this disparity, and likely influence African Americans’ increased risk of CKD through multiple pathways. Low socioeconomic status (SES) may contribute to racial disparities in CKD because of the greater prevalence of poverty, for example, among African Americans as compared with whites. However, low SES has a stronger relation with CKD among African Americans than among whites, underscoring that the context and magnitude of socioeconomic influences on CKD outcomes varies between these populations. These socioeconomic influences may produce new or potentiate existing racial differences in biology. This review discusses what is known about the role of SES in explaining racial disparities in CKD, highlights several knowledge gaps in this area, and suggests future directions toward the elimination of disparities in CKD. Semin Nephrol 33:468-475 C 2013 Elsevier Inc. All rights reserved. Keywords: Race, poverty, chronic kidney disease, socioeconomic status, social determinants, African Americans

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frican Americans have long been observed to suffer disproportionately from advanced and progressive chronic kidney disease (CKD) when compared with whites.1,2 Racial differences in socioeconomic factors are believed to contribute to this disparity.3–6 Low income or poverty status is one of the most frequently studied indicators of low socioeconomic status (SES). In 2011, 35% of African Americans lived below the US federal poverty threshold ($22,350 annually for a family of four residing in the continental United States), compared with 13% of whites.7 Poverty has been associated with multiple risk factors for CKD including hypertension,8 diabetes,9 and obesity10; and multiple studies have documented the relation of poverty and CKD.4,5,11–13 Thus, it would be expected that racial disparities in poverty largely might explain the same in CKD. However, the relation of race, poverty, and CKD appears to be far more complex.14 Studies that have examined CKD in populations stratified by income or poverty status have *Division of Nephrology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD. †Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD. ‡Johns Hopkins School of Nursing, Baltimore, MD. §Department of Medicine, San Francisco General Hospital and University of California at San Francisco, San Francisco, CA. Financial support: Supported by the Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation (Princeton, NJ) (D.C.); and, in part, by grant K24DK02643 from the National Institute of Diabetes and Digestive and Kidney Diseases (N.P.). Conflict of interest statement: none. Address reprint requests to Deidra C. Crews, MD, ScM, Johns Hopkins Bayview Medical Center, 301 Mason F. Lord Dr, Suite 2500, Baltimore, MD 21224. E-mail: [email protected] 0270-9295/ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.semnephrol.2013.07.008

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found that SES relates more strongly to CKD among African Americans than whites,4,13 suggesting that socioeconomic influences on CKD outcomes varies between these populations. Understanding these influences, and, in particular, their impact on biological processes, is essential to shifting the focus on documenting disparities to one of eliminating them. In this review, we discuss what is known about the role of SES in explaining racial disparities in CKD, place these data into the broader context of social determinants of health theory, detail several knowledge gaps in this area, and suggest future directions toward the elimination of disparities in CKD.

CONTRIBUTION OF SES TO RACIAL DISPARITIES IN KIDNEY DISEASE End-Stage Renal Disease Studies examining racial differences in kidney disease outcomes often have considered socioeconomic factors that might confound the strong association of African American race with advanced or progressive CKD. These analyses have included measures of SES frequently used in the social and health sciences, including income, education, and occupational status. Although the most readily available, such measures may be imperfect indicators of the complex nature of social and economic influences on health.15 The earliest reports in the kidney disease literature are of the contributions of SES to racial disparities in risk of treated end-stage renal disease (ESRD). In 1991, Whittle et al16 published findings from an ecologic analysis of the Maryland Network 31 ESRD Regional Registry wherein they included area-level prevalence of completion of high school as a potential confounder in their analysis of risk of ESRD resulting from hypertension (534 total cases). They found that Seminars in Nephrology, Vol 33, No 5, September 2013, pp 468–475

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the relative risk of ESRD comparing African Americans with whites was attenuated from 5.6 to 4.5 (95% confidence interval, 3.2-6.2) with the inclusion of education, hypertension, severe hypertension, diabetes, and population age in their analysis. Subsequent studies have found similar contributions of SES to racial disparities in treated ESRD,17–24 with one finding lower area-level SES associated with ESRD incidence only among whites.20 Tarver-Carr et al3 reported in 2002 that sociodemographic factors, including poverty status and educational attainment, accounted for 11.8% of the excess risk of ESRD experienced by African Americans in the United States, based on data from the National Health and Nutrition Examination Survey. In 2008, Volkova et al12 extended prior analyses of the role of SES in racial disparities in ESRD to examine a possible differential relationship of neighborhood poverty (percentage of neighborhood residents living below the poverty threshold) with risk of ESRD among African Americans and whites in three southeastern states. They found that increasing neighborhood poverty was associated with increased ESRD rates for both African Americans and whites; however, the magnitude of the increased ESRD rate was greater for African Americans. Chronic Kidney Disease In an effort to better understand the epidemiology of earlier stages of kidney disease, some recent studies have examined the contribution of SES to racial disparities in non–dialysis-dependent CKD, wherein disparities primarily have been noted in the prevalence of advanced kidney dysfunction2 (eg, estimated glomerular filtration rate [eGFR] o 45 mL/min/1.73 m2) and albuminuria.25,26 As in studies of ESRD, these investigators found inclusion of measures of SES to attenuate, but not eliminate, the relation of African American race and CKD (Table 1). The greatest African American/white disparities were shown by those studies examining advanced or progressive CKD (as opposed to prevalent or incident CKD). Peralta et al27 compared rates of progressive CKD among older adult African Americans and whites in the Cardiovascular Health Study. They found self-reported African American race was associated with 3.2 times greater odds of significant decline in eGFR (Z3 mL/min/1.73 m2 per year) compared with self-reported white race, even after controlling for demographics, diabetes, hypertension, smoking status, education, occupation, and income. McClellan et al5 documented significant disparities in the prevalence of advanced CKD among participants of the REasons for Geographic And Racial Differences in Stroke study, wherein African Americans had 2.2 times greater odds of an eGFR between 10 and 19 mL/min/1.73 m2. This

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study included adjustment for both household and neighborhood-level poverty. Importantly, however, neither of the aforementioned studies included albuminuria in their analyses, which is strongly associated with both African American race and poverty,11,13 and is a key risk factor for advanced or progressive CKD.28–30 Bruce et al31 reported cross-sectional findings from the Jackson Heart Study, a cohort of African American adults, showing that high-income participants had 41% lower odds of prevalent CKD (defined by albuminuria or reduced eGFR) than their poorer counterparts. Of note, subgroup analyses showed that high income was associated statistically significantly with lesser odds of CKD only among men in this study.

RACIAL DIFFERENCES IN THE RELATION OF LOW SES AND CKD Poverty and other indices of low SES such as limited educational attainment and working-class status have been found to be associated with CKD worldwide and across multiple ethnicities.32 Notably, however, in the United States, several recent studies have pointed to a potential differential impact of low SES on risk of non–dialysis-dependent CKD across racial groups (Table 2). Although Merkin et al33 discovered living in a low SES area was associated with a greater risk for progressive CKD only among white men, other studies have found either no difference5 or a stronger association between low SES and African American race.4,13,34,35 Although heterogeneous in their approach, the findings of these studies suggest that, causally speaking, low SES may impact African Americans and whites differently when determining risk of CKD.

SOCIAL DETERMINANTS OF RACIAL DISPARITIES IN CKD Any effort to understand how low SES may differentially impact African Americans’ risk of CKD must take into account the broad scope of the social determinants of health. Regarded globally as the “economic and social conditions that influence the health of people and communities,”36 these factors include a number of upstream and downstream determinants37 as illustrated in Fig. 1. The upstream determinants that may play a role in racial disparities in CKD, but have not been studied extensively, include the following: (1) general socioeconomic, cultural, and environmental conditions; (2) living and working conditions (including access to healthy foods); and (3) social and community networks. The downstream social determinants of racial disparities in CKD are those to which racial differences are attributed most

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Table 1. Studies of CKD Examining SES as an Explanatory Factor for African American/White Disparities Study

Year

Data source(s)

Peralta et al27

2006 Cardiovascular Health Study

Martins et al11

2006 National Health and Nutrition Examination Surveys

McClellan 2010 REasons for et al5 Geographic And Racial Differences in Stroke (REGARDS) Study Evans et al79

2011 Atherosclerosis Risk in Communities (ARIC) study

Choi et al80

2011 Diabetes Study of Northern California (DISTANCE)

Outcome

Measure(s) of SES

Major Findings Comparing African Americans With Whites

Prevalent kidney dysfunction Income, education, OR for kidney disease progression or kidney disease and occupation attenuated from 3.8 to 3.2 (95% progression (eGFR CI, 2.5-4.1) with adjustment for decline of Z3 mL/min/ age, sex, smoking, diabetes, 1.73 m2 per y) hypertension, and SES OR for microalbuminuria was 1.98 Prevalent microalbuminuria Household income (95% CI, 1.28-3.06) for poverty or macroalbuminuria greater or less than group; 1.66 (95% CI, 1.01-2.73) 200% of poverty for nonpoverty group; OR for threshold macroalbuminuria was 1.33 (95% CI, 1.11-1.60) for poverty group; 1.17 (NS) for nonpoverty group OR for impaired kidney function Prevalent CKD and impaired Household income increased from 0.7 to 2.2 (1.3-3.9) kidney function below poverty level as GFR category declined from and neighborhood 50–59 to 10-19 mL/min/1.73 m2, poverty including adjustment for age, sex, comorbidities, and SES HR attenuated from 1.6 to 1.2 (95% Incident CKD (eGFR o60 Annual household CI, 1.0-1.45) after adjustment for mL/min/1.73 m2 or income, education, age, sex, estimated GFR, access to health hospitalization or death smoking, alcohol use, and SES care, and health with CKD) insurance HR attenuated from 1.4 (age and Incident albuminuria Education, income, sex adjusted) to 1.3 (95% CI, 1.1assets, 1.4) with adjustment for clinical neighborhood factors and SES deprivation index

Abbreviations: CI, confidence interval; HR, hazard ratio; OR, odds ratio; NS, non-significant P value.

frequently and include individual lifestyle factors and constitutional factors (eg, genetic background).

General Socioeconomic, Cultural, and Environmental Conditions In addition to the economic disadvantage suffered by many African Americans as detailed earlier, the social/ cultural construct of race itself may pose health challenges through the mechanisms of racial discrimination and/or stress related to racial identity. Although little is known about racial discrimination and CKD, several studies have documented the association of racial discrimination with poor blood pressure outcomes among African Americans,38 which likely is related to the stress response.39 Psychosocial stressors may lead to impairments in the autonomic nervous system’s ability to respond appropriately, which ultimately can lead to deleterious health consequences. For example, low SES has been correlated with little variation in heart rate (low heart rate variability),40,41 and some studies have shown African Americans to have lower heart rate variability relative to that of whites.40,42,43 Among its association with multiple chronic diseases, low heart rate variability has been shown to predict incident ESRD.44

Environmental conditions that may lead to differential effects of low SES on African Americans include racial differences in exposure to heavy metals, industrial chemicals, and infectious agents. Certain low SES populations may be more exposed to lead,45 and race appears to modify the associations of lead with albuminuria and reduced eGFR, with African Americans having the strongest association.46 Also, although not well documented, it is possible that exposure to acutely nephrotoxic infectious agents such as hantavirus47 could differ among ethnic groups. Living and Working Conditions Neighborhood of residence and living conditions may play an important role in the apparently greater impact of low SES on CKD among African Americans. Racial residential segregation is a well-established driver of social disadvantage for African Americans because place of residence is the primary determinant of access to quality education and employment opportunities.48 Although understudied in CKD, Kershaw et al49 reported that racial disparities in hypertension were significantly smaller in low than in high areas of racial segregation, a difference that was not explained by variations in neighborhood-level poverty. Furthermore,

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Table 2. Studies Examining the Contribution of SES to CKD in Different Racial/Ethnic Groups Study

Year

Merkin et al33

2005 ARIC study

Shoham et al35

2007 Life Course Socioeconomic Status Study (ancillary study of ARIC)

Shoham et al34

Data source(s)

Outcome

Major Findings

Living in a low SES area was Progressive CKD during Area-level SES associated independently with (income, wealth, 9 years of follow-up greater risk for progressive CKD education, and evaluation, only among white men occupation) hospitalization for CKD or death Prevalent CKD (eGFR Trend toward working class Income, education, o45 mL/min/1.73 m2) membership was associated more occupation, and strongly with CKD among African social class at critical Americans than whites periods in the life (P interaction ¼ .07 for race and course father having been a farmer) Prevalent CKD (eGFR Trend toward cumulative working Social class and o45 mL/min/1.73 m2) class status across the life course neighborhood was associated more strongly with socioeconomic CKD among African Americans conditions than whites (P interaction ¼ .22) Prevalent CKD (eGFR Poverty status Low SES was associated with CKD o60 mL/min/1.73 m2) among African Americans but not among whites (P interaction ¼ .003)

2008 Life Course Socioeconomic Status Study (ancillary study of ARIC) Crews 2010 Healthy Aging in et al4 Neighborhoods of Diversity across the Life Span (HANDLS) study Prevalent CKD and McClellan 2010 REasons for impaired kidney et al5 Geographic And function Racial Differences in Stroke (REGARDS) study Crews et al13

Measure(s) of SES

Prevalent albuminuria 2012 Reasons for (high or very high Geographic and urinary ACR) Racial Differences in Stroke (REGARDS) study

Household income below poverty level and neighborhood poverty

Household income

Household income, but not neighborhood poverty, was associated with CKD in both African Americans and whites, with a nonsignificant P interaction for race and household income Trend toward stronger association of low income and high ACR among African Americans than whites (P interaction ¼ .08)

Abbreviations: ACR, albumin-to-creatinine ratio; ARIC, Atherosclerosis Risk in Communities.

in the Moving to Opportunity Study, participants who were assigned randomly to receive a voucher to move from a high-poverty neighborhood to a low-poverty neighborhood experienced lesser rates of extreme obesity and diabetes mellitus 10 to 15 years later, as compared with those who did not move from the highpoverty neighborhood.50 Neighborhood of residence can influence the availability of healthy foods, which may impact African Americans’ risk of CKD through multiple pathways (Fig. 2). We posit that limited availability of healthy food leads to poor dietary patterns among many low SES African Americans, which can affect risk of incident CKD and/or CKD progression through both direct and indirect mechanisms. A potential direct effect of poor diet on CKD would be the release of kidney endothelins in response to acid-inducing diets (ie, limited fruits and vegetables), which could lead to endothelinmediated glomerulosclerosis and fibrosis.51 Endothelin-1, for example, is a marker of endothelial injury that is associated independently with albuminuria.52 Indirect effects of poor diet on CKD would include the

extent to which other chronic diseases (eg, diabetes and hypertension) result from such diets. African Americans are more likely to experience food insecurity (the inability to afford nutritionally adequate and safe foods)53 and live in food deserts (areas where lowincome residents do not have access to healthy food and fast food restaurants predominate),54 which may contribute to racial differences in dietary patterns. African Americans with hypertension are less likely to follow a Dietary Approaches to Stop Hypertension trial–accordant diet than are whites,55 despite their being shown the potential to undergo the greatest blood pressure benefit from the diet.56 Further, African Americans are less likely to follow baseinducing diets (rich in fruits and vegetables),57 despite the proven potential benefits of these diets (eg, albuminuria reduction), especially in the setting of hypertensive nephropathy.58 Social and Community Networks Little is known about the impact of social and community networks on CKD outcomes, however,

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Figure 1. Conceptual framework of the social determinants of health. Reprinted with permission from Dahlgren and Whitehead.81

studies have shown that social support may buffer the detrimental effect of stress59 and enhance access to opportunities such as employment and housing that can positively influence health.60 Further, neighborhood social cohesion has been associated with lesser prevalence of hypertension in the Multi-Ethnic Study of Atherosclerosis61 and social integration has been associated with diabetes management behaviors among older adults with diabetes.62 Victor et al63 made use of the barbershop social network of the African American male community to conduct a hypertension intervention. They found that hypertension control increased by 8.8% when barbers were trained as health educators.

Limited Availability of Healthy Food • Food Insecurity • Lack of Healthy Foods in Home • Lack of Cooking Appliances • Lack of Full Service Grocery Stores in Neighborhood

Poor Dietary Patterns • High Sodium Intake • Intake of Processed Foods • Limited Fruits and Vegetables

Individual Lifestyle Factors Although largely shaped by upstream social determinants of health, individual lifestyle factors likely play an important role in the impact of SES on CKD among African Americans. Rates of lifestyle-related conditions associated with increased risk of CKD such as obesity64 and human immunodeficiency virus (HIV) infection65 are alarmingly high among African Americans, and in several cases are highest among those of low SES.66 African American women bear a particularly disproportionate burden of lifestyle-related conditions, and this is not fully explained by differences in SES, arguing that other factors (eg, stress, poor coping) may explain their inability to lead healthful lifestyles.67,68

CKD Risk Factors • Obesity • Diabetes • Hypertension

Incident CKD and CKD Progression

Figure 2. Conceptual framework of dietary determinants of CKD among African Americans with low SES.

Socioeconomic factors and racial disparities

Constitutional Factors Low SES may differentially influence African Americans' risk of CKD because of genetic differences between African Americans and whites. Racial differences in the apoliprotein L1 (APOL1) risk variant frequency has been shown, for example, to explain much of the excess risk of nondiabetic nephropathy observed among African Americans.69 Importantly, however, not every individual with two APOL1 risk variants develops ESRD. Thus, “second-hits” are probable, including potential gene–environment interactions.70 The upstream social determinants of health may be these second-hits. HIV infection, for example, leads to 50-fold higher rates of HIVassociated nephropathy among African Americans as compared with whites,71 a disparity now believed to be largely owing to APOL1 risk variant differences.72 Gene–environment interactions related to APOL1 and SES have not been well examined. However, analyses of African ancestry, more generally, have not supported an interaction of ancestry and SES in contributing to racial disparities in CKD. Through their assessment of ancestry informative markers, Peralta et al27 reported no association between level of African ancestry and kidney dysfunction. They did, however, find strong associations between income and kidney dysfunction. We conducted some preliminary work in the Healthy Aging in Neighborhoods of Diversity across the Life Span study, and similar to Peralta et al,27 found no association between African ancestry and albuminuria, but did find income and albuminuria to be correlated.73 Neither study reported significant interactions between African ancestry and SES.

CONCLUSIONS Socioeconomic factors are likely to contribute to racial disparities in CKD through many different mechanisms. Research is beginning to identify several of the pathways that might lead to more rapid kidney disease progression in minorities. Some of these are likely to be modifiable, such as diet and physical activity. However, despite emerging reports of promising dietary and other lifestyle interventions for slowing progression of CKD,58,74–77 there is a need to translate these interventions effectively into sustainable programs for low SES ethnic minorities. Furthermore, studies of SES should be broadened to include periods of potential harmful exposures across the life-course, including the prenatal and perinatal periods,78 and inclusion of genetic markers to advance understanding of gene–environment interactions. Finally, members of the renal community must become more engaged in public policy initiatives, through which we are

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afforded the greatest opportunity to influence the social determinants of CKD.

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