Ethnicity and Chronic Kidney Disease—United States

C H A P T E R

8 Ethnicity and Chronic Kidney DiseasedUnited States Keith C. Norrisa, Allen R. Nissensona,b a

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, United States; b DaVita, Inc., Denver, CO, United States peers.4,5 This chapter describes the current status of CKD and ESRD risk, complications, and care in the US and explores the social and biologic factors that interact to influence racial/ethnic differences in CKD/ESRD risk and outcomes.

Abstract Chronic kidney disease (CKD) is a noncommunicable disease that is now well recognized as a major cause of premature morbidity and mortality. Racial/ethnic minorities have an increased prevalence of key risk factors such as diabetes mellitus and hypertension, as well as being 1.5e3 times more likely than their non-Hispanic White counterparts to reach end-stage renal disease (ESRD). While the term race represents a social/political construct, its association with health is complex. The term race is actually a misnomer as Homo sapiens is the only extant human species, so there is only one race. Thus, variations in groups of humans that share similar physical appearances, language, culture, and/or biology linked to ancestral geographic origins might more appropriately be classified as ethnicity. Understanding how the race/ ethnicity interacts to influence CKD and ESRD risk, progression, and complications in the US is critical to advancing the care of all patients with kidney disease.

HEALTHY PEOPLE 2020

INTRODUCTION We don’t see things as they are, we see them as we are Anais Nin (1903e1977)

Chronic kidney disease (CKD) is epidemic in the US. CKD is a noncommunicable disease that is now well recognized as a major cause of premature morbidity and mortality.1 Multiple aspects of CKD, ranging from the risk and development to progression and complications, differ by race/ethnicity and are among the starkest examples of health disparities in the US.2,3 This is highlighted by racial/ethnic minorities having a nearly 2-fold higher incidence rate of diabetes mellitus (DM), the leading cause of CKD, as well as a 1.5- to 3-fold greater incidence of end-stage renal disease (ESRD) compared with their age-adjusted non-Hispanic White Chronic Renal Disease, Second Edition https://doi.org/10.1016/B978-0-12-815876-0.00008-5

The elimination of racial and ethnic disparities across all stages of CKD is widely recognized in nephrology as an important approach to understand and ultimately improve overall patient outcomes.2,6e8 It is also one of the target areas for Healthy People 2020, our nation’s blueprint for health.9 The finding of increased rates of ESRD among racial/ethnic minorities Americans in the late 1970s and early 1980s10e12 prompted the need to better understand the issues underlying both ESRD incidence and quality care for all groups of patients receiving renal replacement therapy (RRT).13e16 A response to these early findings was the introduction of national ESRD performance measures and quality standards.17,18 These national performance measures have led to a substantial improvement in the quality of care and a reduction in disparities for patients receiving RRT.17,18 However, our work has just begun. In evaluating kidney disease-related racial/ethnic disparities, it is critical that we view this issue through two distinct lenses, one viewing race as a social construct and one as ancestral biological variants. Thus, outcomes for patients in varying settings with or at risk for CKD are influenced by the social determinants of health, juxtaposed with geo-evolutionary risk and resilience gene variants. Through this understanding, the nephrology community can move closer to creating more effective

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solutions to eliminate disparities and to use the lessons learned to improve outcomes for all patients.

DEFINING RACE AND ETHNICITY The concept and use of the terms race and ethnicity are deeply integrated into our nation’s social fabric. There is no generally agreed on definition for these terms, but it is clear that they carry complex nuances reflecting social position, political status, culture, economics, and history juxtaposed with differing frequencies of particular gene variants that reflect ancestral geographic origins.19 Race and ethnicity can mean different things to different people, may have different implications in different settings, and a person’s designation can change in a particular place and/or time. Historically, the use of the term race in the US derives from Carl Linnaeus, the father of modern taxonomy. Linnaeus designated four major “racial” groups by geographic region (Europe, Asia, Americas, and Africa), and then assigned each racial category select personality traits, skills, and abilities,20 with the more desirable traits ascribed to White Europeans and the least desirable traits ascribed to Black Africans. This designation was viewed as an actual scientific fact and helped to establish the “scientific” foundation for racism.21 By contrast, the actual science, including recent DNA analysis of different groups of people, confirmed that there are in fact no distinct populations within or that differ from modern Homo sapiens.22 However, the US Census reporting still uses the original Linnaeusbased race categoriesdWhite, American Indian or Alaska Native, Asian, and Black or African Americand with a fifth category added in 2000 for Native Hawaiian or other Pacific Islander.23e25 The US Office of Management and Budget uses two major ethnic categories for each person: (1) not Hispanic or Latino and (2) Hispanic or Latino, regardless of race.23,24 Clearly a decision to divide the world into two ethnic groups also has no scientific merit. These categories thus reflect not scientific differences among groups but the social, political, cultural, economic, and historical influences that provide access and opportunity in a society and its impact on multiple dimensions of being, including health. A scientifically accurate view that humans are a single race is held by the Pan American Health Organization/World Health Organization, which does not use the term race and uses the term ethnicity to capture differences between groups of individuals that share common linguistic, cultural, and ancestral backgrounds.26 Consistent with this, the terms “ethnicity” and “race” will be used as the combined term race/

ethnicity in this chapter, not only recognizing that different races do not exist but different ethnic groups do but also acknowledging that the use of the term race persists in the US for categorizing people by governmental agencies, including health and educational systems.26

RACE/ETHNICITY AND HEALTH Racial/ethnic minorities now comprise nearly 40% of the US population,27 highlighting the importance of optimizing minority health to improve the overall health of our nation. However, given the political and social underpinnings of race and ethnicity in the US, and the persistence of structural racism, it is not surprising that minorities continue to suffer from worse health outcomes in most domains. This is because health outcomes stratified by race/ethnicity are strongly influenced by a group’s social position/exclusion, marginalization, discrimination, and the associated socioecologic determinants of health such as residential segregation,28 educational and income inequalities,29e32 imbalance in community-level assets, access to care,6 health care resources,33e35 and exposure to environmental toxins.7,36 Additional factors include health system barriers, unconscious provider biases, medical mistrust, patient beliefs and behaviors, and stereotype threat.37e40 Stereotype threat is a more recently recognized concept in health care and refers to the fear of being judged by, and/or confirming through one’s own actions, negative group stereotypes that operate within the domain of health care, such as inferior intelligence, lower social status, greater likelihood of engaging in risky behaviors, and less deserving of high quality care.39 Despite the passing of civil rights legislation in the 1960s, the above issues are promulgated by judicial and institutional policies, practices, and beliefs that maintain many of the racialized precivil rights structural elements and thus perpetuate many of the persisting disparities by race/ethnicity and gender.

CKD PREVALENCE AND MAJOR CHRONIC KIDNEY DISEASE RISK FACTORS Based on estimates from the National Health and Nutrition Examination Survey (NHANES), the overall prevalence of CKD in the US has slowly increased, and this increase is present in all racial/ethnic groups. The 1988-1994 NHANES compared with the 2011-2012 NHANES estimated prevalence of CKD stages 1e4 for

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SOCIAL DETERMINANTS OF HEALTH

TABLE 8.1 Select Chronic Kidney Disease Risk Factors by Ethnicity Hispanic

Asian

Native American

Black/African American

White

Prevalence of age-adjusted diagnosed diabetes for adults aged 18 years or older, 2013e2015 (%)46

12.1

8

15.1

12.7

7.4

Age-adjusted prevalence of hypertension among adults aged 18 and over, 2015e2016 (%)47,48

27.8

25.0

26.4

40.3

27.8

Age-adjusted prevalence of controlled hypertension among adults with hypertension aged 18 and over, 2015e2016 (%)47

45

37.4

Not available

44.6

50.8

Prevalence of overweight/ obese (age-adjusted) (%)27

69.9

42

70.5

72

64.1

TABLE 8.2 Select Socioeconomic Factors by Race/Ethnicity Hispanic

Asian

Native American

Black/African American

White

Self-reported overall health status as fair or poor27

25.2

10.8

28.7

22.1

16.4

% Below federal poverty level27

16

9

22

20

8

Uninsured, nonelderly

19

7

22

11

7

Graduation rate from public high school (%)50

79

91

72

76

88

No personal doctor or health care provider27

39

23

29.2

22.3

18

27

non-Hispanic Whites at 11.8 vs. 14.1%, non-Hispanic Blacks 13.7 vs. 17.3%, and for other 10.1 vs. 12.7%.41 However, when the estimates were restricted to CKD stages 3 and 4, the authors found the rates for nonHispanic Whites at 5.4 vs. 8.0%, non-Hispanic Blacks 3.7 vs. 6.2%, and for other 2.2 vs. 3.6%.41 These findings suggest White patients with CKD are more likely to progress to stages 3 and 4 but appear less likely to progress to ESRD, especially because racial/ethnic minorities have a higher mortality rate among persons with CKD, especially those below 65 years of age.42 Diabetes and hypertension are the two leading causes of patients progressing to ESRD.43 In addition, obesity/ overweight is an emerging CKD risk factor as well as a noncommunicable public health epidemic, whereas albuminuria is an important CKD progression factor. Compared with their White peers, most racial/ethnic minorities have a higher prevalence of diabetes, hypertension, and obesity/overweight, as well as albuminuria (Table 8.1).27,44,45

SOCIAL DETERMINANTS OF HEALTH The self-reported overall health status varies by race/ ethnicity, with 20.5% of African Americans, 25.6% of Hispanics, 27% of Native Americans, 9% of Asians, and 15.7% of Whites reporting fair or poor health status.27 This discrepancy is driven in part by many of the social determinants of health, which disproportionally affect minority and low-income populations adversely. Social determinants of health include factors such as access to providers/care, educational attainment, income, insurance, and community-level assets and deficits.3,49 In general, compared with their White peers, racial/ethnic minorities are more likely to report having no personal doctor or health care provider, be below the federal poverty line, be uninsured, and have lower graduation rates at public high schools (Table 8.2).27,50 These adverse social characteristics are highly relevant for patients with CKD. An analysis of participants with or at risk for CKD in the National Kidney Foundation

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Kidney Early Evaluation Program (KEEP) screening program found uninsured KEEP participants were 72% more likely to develop ESRD and 82% more likely to die than those with private insurance.51 Similarly, Choi et al. found a nearly 20% higher adjusted relative risk of death for KEEP participants with CKD and less than high school education, compared with those with high school education or greater, followed over a mean follow-up period of 3.9 years.31 A situation similar to limited educational attainment exists regarding low levels of literacy. An analysis of participants in the Chronic Renal Insufficiency Cohort study found 28% of African Americans and 5% of Whites had limited health literacy.52 Limited health literacy in patients with CKD has been associated with increased hospitalizations, emergency department use, cardiovascular events, and mortality.53 Cavanagh and colleagues found limited health literacy in dialysis patients was associated with a 54% higher risk for death and was more likely in be present in males, racial/ethnic minorities, and those with fewer years of education.54 Thus, adverse social determinants of health have a major impact on CKD outcomesand they remain disproportionately prevalent in many racial/ethnic minority communities.

However, for CKD and major CKD-specific quality care metrics, there has been more substantial improvement noted by Healthy People 2020 (Table 8.4).43,56 This includes a substantial increase in and reduced disparity over the last 10e12 years in the percent of racial/ethnic minorities diagnosed with DM who obtained an annual evaluation of urinary albumin, the percent of persons with DM and CKD who received a more comprehensive medical assessment and received recommendation regarding medical treatment with inhibitors of the renin angiotensin system, the percent of patients receiving care from a nephrologist at least 12 months prior to the start of RRT and others (Table 8.4). Because the number of patients receiving RRT has increased while the number of kidney transplants has remained flat, the percent of all patients receiving a kidney transplant has progressively fallen (Table 8.4). Interestingly, despite an overall decline in the death rate for patients receiving dialysis treatments, the death rate for White dialysis patients remains above the Healthy People 2020 target level (Table 8.4). The reason for this observation is not clear, but a possible survival bias could lead to healthier minorities reaching dialysis or other resilience factors in the setting of chronic disease could account for the observed differences.42,57e61

CKD QUALITY OF CARE The Agency for Healthcare Research and Quality examined racial/ethnic differences in 182 national quality measures and reported areas where there was improvement, no difference or worsening. They found, compared with White patients, no difference or worsening in 87% of quality measures for Blacks, 78% for Hispanics, 87% for American Indian/Alaskan Natives, 76% for Native Hawaiian/Pacific Islanders, and 66% for Asians.55 In addition, Blacks, Hispanics, and American Indian/Alaskan Natives had worsening in more than twice as many quality of care measures than they had improvement.55 Details regarding improvement, no difference, or worsening of quality measures by race/ethnicity are provided in Table 8.3.

TABLE 8.3

ESRD TREATMENT MODALITIES Despite a fairly similar prevalence of the early stages of CKD, and a lower prevalence of CKD stages 3 and 4, racial/ethnic minorities are 1.5e3 times more likely than their non-Hispanic White peers to progress to ESRD and require RRT.4,5,41 In the US, the preferred options for RRT are kidney transplantation or home dialysis,62 yet, racial/ethnic minorities are less likely to receive RRT with either a kidney transplant or home dialysis therapy.63 These findings highlight the continuing need for efforts to achieve greater equity in the use of the preferred ESRD treatment options.

Agency for Healthcare Research and Quality Racial/Ethnic Differences in 182 National Quality Measures Compared with Whites (Not all Measures Included all Groups, so Totals May Not ¼ 182)

Change in Quality Metrics

Hispanic

Asian

American Indian/ Alaskan Natives

Black/African American

Native Hawaiian/ Pacific Islanders

Improved (n)

37

55

12

23

12

No difference (n)

66

76

50

82

24

Worsened (n)

65

32

31

77

14

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IMPACT OF CHANGES IN ESRD REGULATORY PRACTICES ON RACIAL/ETHNIC DISPARITIES

TABLE 8.4 Healthy People 2020 (HP 2020) Select Markers of Chronic Kidney Disease (CKD) Care by Race/Ethnicity Hispanic

Asian

Native American

Black/African American

White

HP 2020 Target

% Persons with diagnosed DM who obtain an annual urinary microalbumin measurement

50.5 (2015)

53.4 (2015)

30.1 (2015)

46.0 (2015)

47.5 (2015)

37 (2015)

31.5 (2006)

33.8 (2006)

19.8 (2006)

29.5 (2006)

31.4 (2006)

31 (2006 average)

% Persons with DM and CKD who receive medical evaluation with serum creatinine, lipids, and A1c, microalbuminuria, and eye exams

32.1 (2015)

32.9 (2015)

18.0 (2015)

27.6 (2015)

30.2 (2015)

25.3 (2015)

20.3 (2006)

26.2 (2006)

12.4 (2006)

18.8 (2006)

21.4 (2006)

21.2 (2006 average)

% Persons with DM and CKD who receive recommended medical treatment with ACEI or ARB

77.1 (2015)

76.5 (2015)

74.4 (2015)

72.3 (2015)

70.2 (2015)

76.3 (2015)

69.1 (2006)

70.3 (2006)

60.2 (2006)

66.7 (2006)

62.2 (2006)

63.6 (2006 average)

% CKD patients receiving nephrologist care at least 12 months before start of renal replacement therapy

28.1 (2015)

37.6 (2015)

34.9 (2015)

32 (2015)

37 (2015)

30.4 (2015)

19.8 (2006)

23.9 (2006)

27.3 (2006)

23.2 (2006)

27.9 (2006)

26.4 (2006 average)

Rate of new cases of ESRD/million population

492 (2015)

314.9 (2015)

376 (2015)

895 (2015)

312.1 (2015)

352 (2015)

21.1 (2006)

355.4 (2006)

526.9 (2006)

1114 (2006)

294 (2006)

398.9 (2006 average)

% Patients receiving a kidney transplant within 3 years of ESRD

11.0 (2012)

16.2 (2012)

7.2 (2012)

7 (2012)

16.2 (2012)

20.1 (2012)

14.7 (2006)

19.1 (2006)

10.0 (2006)

9.1 (2006)

21 (2006)

17.2 (2006 average)

Number of deaths per 1000 patient years for persons on dialysis

128.5 (2015)

126.4 (2015)

152.9 (2015)

135.8 (2015)

207.4 (2015)

187.4 (2015)

156.9 (2006)

153.7 (2006)

171.1 (2006)

170.9 (2006)

258.1 (2006)

216.7 (2006 average)

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; DM, diabetes mellitus; ESRD, end-stage renal disease. Source: USRDS 2017.43

ESRD QUALITY CARE METRICS Ongoing quality improvement measures have eliminated individual-level racial/ethnic disparities for most metrics such as dialysis adequacy and anemia. Interestingly, disparities persist at the facility level, with lower levels of dialysis adequacy and higher rates of anemia reported in patients treated in dialysis facilities within neighborhoods with a higher proportion of African Americans.64,65 These disparities persist even after controlling for neighborhood-level socioeconomic status and other factors in some,64 but not all, studies.65 Interestingly, when examining facility-level hemoglobin (Hb) targets by the percentage of African-Americans patients per facility, rather than by neighborhood, there was no difference in anemia-related quality measures.65 These findings reinforce the need to better understand and further explore the social determinants of health that drive facility/community-level outcomes to further advance efforts to achieve equity in treatment care at dialysis facilities, regardless of facility location or patient case mix.

IMPACT OF CHANGES IN ESRD REGULATORY PRACTICES ON RACIAL/ ETHNIC DISPARITIES Although there has been progressive improvement in quality care for racial/ethnic minorities over the last 25 years, concerns have been raised that these gains may have been negated by the implementation of the 2011 Medicare ESRD prospective payment system (PPS) and the simultaneous FDA-mandated manufacturer label changes to lower recommended Hb targets. Either of these could lead to more restricted erythrocyte-stimulating agent (ESA) use, increased rates of anemia, and subsequently worse outcomes.66,67 Medicare ESRD PPS changes could also lead to poorer bone and mineral disorder (BMD) outcomes.67 Anemia and BMDs are of particular concern, given the historically higher doses of ESA and vitamin D needed to maintain target Hb and parathyroid hormone (PTH) levels, respectively, in Blacks. A pre-post PPS analysis by Turenne and colleagues of over 7000 patients treated at 132 dialysis facilities from the Dialysis Outcomes and

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Practice Patterns Study Practice Monitor found overall mean Hb levels fell from 11.5 to 11.0 g/dL and mean EPO dose declined from 20,506 to 14,777 U/week, with no meaningful differences by race/ethnicity.68 Similar to the potential impact of anemia management and outcomes, the PPS is likely to affect the dosing of vitamin D and related medications used to treat BMDs. The dose of vitamin D needed to maintain target PTH levels and the relationship between PTH levels, serum phosphate levels, and fibroblast growth factor 23, and bone fractures, bone histology, or mortality differs across racial/ethnic groups.68e73 Following the implementation of 2011 Medicare ESRD PPS cost-saving measures, Turenne et al. found mean serum iPTH increased from 340 to 435 pg/mL, but these changes did not differ by race/ethnicity.68 In addition, Wang et al. examined cardiovascular outcomes following the PPS and ESA labeling changes in 2011 and found no overall difference before and after the changes among fee-for-service Medicare patients, with the exception of an 18% reduction in cardiovascular events that was observed in a secondary analysis of Black patients, suggesting the new policies had no adverse impact overall or by race/ethnicity, with a possible beneficial effect on Black patients.74

PRE-ESRD NEPHROLOGIST CARE AND VASCULAR ACCESS Several markers of pre-ESRD care are linked to outcomes for patients receiving RRT, and the lack of or delay in establishing pre-ESRD care is associated with increased risk of death following transition to RRT.75e77 Unfortunately, there has been little change over the last 15e20 years in the disparities related to pre-ESRD nephrology care.75e79 Despite the introduction of the ESRD (and pre-ESRD) quality care initiatives in the early 1990s, Gillespie et al. reported in 2015 that more than 12 months of pre-ESRD care was less frequent in African Americans, Asians, Native Americans, and Hispanics.76 These findings are reinforced by a report from Yan et al. who found a lower state-level probability of Blacks having received nephrologist care 12 months prior to dialysis, more so in younger Black patients.80 The finding was attenuated for older Blacks, who were more likely to have had Medicare insurance coverage during the per-ESRD period, suggesting insurance has a major influence on racial disparities in the pre-ESRD period.80 Although the use of an arteriovenous fistula (AVF) at first hemodialysis treatment is associated with superior clinical outcomes, the use of an AVF at the first dialysis treatment remains a major area of racial/ethnic and gender disparities in dialysis care.81,82 Analyzing a cohort of nearly 400,000 dialysis patients, Zarkowsky

et al. found Hispanic and Black patients were less likely to initiate hemodialysis with an AVF than their non-Hispanic White peers, independent of insurance status, despite having fewer comorbidities and being younger.83 Like pre-ESRD nephrologist visits, factors in addition to insurance, such as medical mistrust, health system barriers, health literacy, provider and patient biases, social determinants, and others that could account for these differences, require further investigation to create policies which might eliminate or diminish pre-ESRD disparities.7,38,40,83,84

SURVIVAL ON DIALYSIS Despite higher rates of lower quality of ESRD care, observational data have consistently shown that racial/ethnic minorities receiving dialysis treatments have greater survival rates than their peer majority groups, even after adjusting for age, gender, and transplantation.57e60,85e90 The observation that minority groups treated with dialysis have greater survival than their majority peers is not limited to the US.86e88 In the US, Hispanics have a higher adjusted survival rate than non-Hispanics at every age, whereas the BlackWhite survival difference appears to vary by age, as there are significantly better survival rates for Blacks above 40 or 50 years of age compared with Whites, but younger Black and White patients have similar survival rates.57,58,60 Asians also have a higher survival rates than Whites,91 but due to fewer numbers of Asian ESRD patients, few comparative subgroup analyses have been feasible to date. Community factors also influence dialysis outcomes. Facilities located in communities with higher proportions of Black patients (typically characterized by lower community SES and fewer health-related community assets) have poorer survival outcomes among both Black and non-Black patients.35,64,65,92 These findings reinforce the notion that intertwined social and economic influences may have important implications for ESRD patient outcomes.

CONCLUSION Social and to a lesser extent biological factors appear to contribute to the more frequent need for RRT for racial/ethnic minorities, where access to and quality of care, patient behaviors, control of medical risk factor conditions, and other factors combine with CKD risk alleles to influence CKD development and progression.3,38 Once progression to ESRD has occurred, the impact of risk factors in different race/ethnic groups may vary substantially for different quality measures and

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REFERENCES

outcomes. The impact of longstanding racialized policies and practices on the social positioning of racial/ethnic groups, and associated barriers such as limited finances, inadequate health insurance, medical distrust, unconscious provider biases, that may result in differential clinical practice decision-making and related factors influencing patients’ beliefs and behaviors together, may contribute to persistent disparities in the likelihood of receiving different care for CKD, pre-ESRD, and RRT.2,6,7,29,33,84 Importantly, as the medical and health sciences professions identify health-related differences between racial groups, the lessons learned should not only prompt new biomedical advances including personalized medicine but also stimulate advocacy for social and health policy level changes that can promote equity while ensuring the highest quality of care within our health systems and dialysis facilities, to ultimately achieve health equity and improve outcomes for all patients.93e95

Funding/Support KN is supported in part by NIH research grants UL1TR000124 and P30AG021684.

Financial Disclosures Neither of the other authors declare any relevant conflicts of interest.

References 1. Eknoyan G, Lameire N, Eckardt K, et al. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 2013;3:5e14. 2. Nicholas SB, Kalantar-Zadeh K, Norris KC. Racial disparities in kidney disease outcomes. Semin Nephrol 2013;33(5):409e15. 3. Nicholas SB, Kalantar-Zadeh K, Norris KC. Socioeconomic disparities in chronic kidney disease. Adv Chron Kidney Dis 2015;22(1): 6e15. 4. USRDS. United States Renal Data System. 2015 USRDS annual data report: epidemiology of kidney disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2015. 5. Hsu CY, Lin F, Vittinghoff E, Shlipak MG. Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States. J Am Soc Nephrol 2003;14(11):2902e7. 6. Powe NR. Let’s get serious about racial and ethnic disparities. J Am Soc Nephrol 2008;19(7):1271e5. 7. Norris K, Nissenson AR. Race, gender, and socioeconomic disparities in CKD in the United States. J Am Soc Nephrol 2008;19(7): 1261e70. 8. Norris KC, Agodoa LY. Unraveling the racial disparities associated with kidney disease. Kidney Int 2005;68(3):914e24. 9. US Department of Health and Human Services: Healthy people 2020: chronic kidney disease. Available from: https://www. healthypeople.gov/2020/topics-objectives/topic/chronic-kidneydisease.

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10. Rostand SG, Kirk KA, Rutsky EA, Pate BA. Racial differences in the incidence of treatment for end-stage renal disease. N Engl J Med 1982;306(21):1276e9. 11. Dillard MG, Callender CO. End-stage renal disease in blacks: a national or international problem? J Natl Med Assoc 1984;76(12): 1157e8. 12. Easterling RE. Racial factors in the incidence and causation of end-stage renal disease (ESRD). Trans Am Soc Artif Intern Organs 1977;23:28e33. 13. Wright Jr JT, Kusek JW, Toto RD, et al. Design and baseline characteristics of participants in the African American Study of Kidney Disease and hypertension (AASK) pilot study. Contr Clin Trials 1996;17(4 Suppl. l):3se16s. 14. Feldman HI, Klag MJ, Chiapella AP, Whelton PK. End-stage renal disease in US minority groups. Am J Kidney Dis 1992;19(5):397e410. 15. Norris K, Owen Jr B. Minorities and ESRD: have we seen improvements in care? Nephrol News Issues 1997;11(2):66e8. 16. Reddan DN, Szczech LA, Klassen PS, Owen Jr WF. Racial inequity in America’s ESRD program. Semin Dial 2000;13(6):399e403. 17. Sehgal AR. Impact of quality improvement efforts on race and sex disparities in hemodialysis. J Am Med Assoc 2003;289(8):996e1000. 18. Owen Jr WF, Szczech LA, Frankenfield DL. Healthcare system interventions for inequality in quality: corrective action through evidence-based medicine. J Natl Med Assoc 2002;94(8 Suppl. l): 83se91s. 19. Collins FS. What we do and don’t know about ’race’, ’ethnicity’, genetics and health at the dawn of the genome era. Nat Genet 2004;36(11 Suppl. l):S13e15. 20. Linnaeus C. Systema naturae. 1735. 21. Harawa NT, Ford CL. The foundation of modern racial categories and implications for research on black/white disparities in health. Ethn Dis 2009;19(2):209e17. 22. Marshall E. DNA studies challenge the meaning of race. Science 1998;282(5389):654e5. 23. Directive OS. 15. Standards for maintaining, collecting, and presenting federal data on race and ethnicity. Fed Regist 1997:30. 24. Registrar F. Revisions to the standards for the classification of federal data on race and ethnicity. Fed Regist 1997;62:58781e90. 25. Pew Research Center. What census calls us: a historical timeline. 2015. Available from: http://www.pewsocialtrends.org/interactives/ multiracial-timeline/. 26. Ethnicity and Health. Pan American Health Organization/World Health Organization. In: 132nd session of the executive committee. Washington, D.C., USA; 23e27 June 2003. Available from: http:// www1.paho.org/english/gov/ce/ce132-16-e.pdf. 27. Kaiser Family Foundation. State health facts. 2018. https://www. kff.org/state-category/minority-health/. 28. Bruce MA, Beech BM, Sims M, et al. Social environmental stressors, psychological factors, and kidney disease. J Investig Med 2009;57(4): 583e9. 29. De La Cruz-Viesca M, Chen Z, Ong PM, Hamilton D, William Jr AD. The color of wealth in Los Angeles. Los Angeles: Report produced by Duke University, The New School, and University of California; 2016. 30. Plantinga LC, Johansen KL, Schillinger D, Powe NR. Lower socioeconomic status and disability among US adults with chronic kidney disease, 1999-2008. Prev Chronic Dis 2012;9:E12. 31. Choi AI, Weekley CC, Chen SC, et al. Association of educational attainment with chronic disease and mortality: the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 2011;58(2):228e34. 32. Young BA. The interaction of race, poverty, and CKD. Am J Kidney Dis 2010;55(6):977e80. 33. Mode NA, Evans MK, Zonderman AB. Race, neighborhood economic status, income inequality and mortality. PLoS One 2016; 11(5):e0154535.

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118

8. ETHNICITY AND CHRONIC KIDNEY DISEASEdUNITED STATES

34. Kimmel PL, Fwu CW, Eggers PW. Segregation, income disparities, and survival in hemodialysis patients. J Am Soc Nephrol 2013;24(2): 293e301. 35. Rodriguez RA, Sen S, Mehta K, Moody-Ayers S, Bacchetti P, O’Hare AM. Geography matters: relationships among urban residential segregation, dialysis facilities, and patient outcomes. Ann Intern Med 2007;146(7):493e501. 36. Crews DC, Liu Y, Boulware LE. Disparities in the burden, outcomes, and care of chronic kidney disease. Curr Opin Nephrol Hypertens 2014;23(3):298e305. 37. World Health Organization. A conceptual framework for action on the social determinants of health. 2010. 38. Boulware LE, Cooper LA, Ratner LE, LaVeist TA, Powe NR. Race and trust in the health care system. Publ Health Rep 2003;118(4): 358e65. 39. Abdou CM, Fingerhut AW, Jackson JS, Wheaton F. Healthcare stereotype threat in older adults in the health and retirement study. Am J Prev Med 2016;50(2):191e8. 40. Narva AS, Norton JM, Boulware LE. Educating patients about CKD: the path to self-management and patient-centered care. Clin J Am Soc Nephrol 2016;11(4):694e703. 41. Murphy D, McCulloch CE, Lin F, et al. Trends in prevalence of chronic kidney disease in the United States. Ann Intern Med 2016; 165(7):473e81. 42. Mehrotra R, Kermah D, Fried L, Adler S, Norris K. Racial differences in mortality among those with CKD. J Am Soc Nephrol 2008;19(7):1403e10. 43. Saran R, Robinson B, Abbott KC, et al. US renal data system 2017 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 2018;71(3S1):A7. 44. Greenburg AD. 1:1 Valerie Schreiner. VP product management/ product marketing. Blackboard. Wainhouse Res Bull 2013;14(5): 7e11. 45. Bryson CL, Ross HJ, Boyko EJ, Young BA. Racial and ethnic variations in albuminuria in the US Third National Health and Nutrition Examination Survey (NHANES III) population: associations with diabetes and level of CKD. Am J Kidney Dis 2006;48(5):720e6. 46. Centers for Disease Control and Prevention. National diabetes statistics report. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2017. 47. Fryar CD, Ostchega Y, Hales CM, Zhang G, Kruszon-Moran D. Hypertension prevalence and control among adults: United States, 2015e2016. NCHS Data Brief 2017;(289):1e8. 48. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 2018;137(12):e67e492. 49. National Center for Health Statistics. Health, United States, 2015: with special feature on racial and ethnic health disparities. 2016. Hyattsville, MD. 50. National center for education statistics public high school graduation rates. 2018. https://nces.ed.gov/programs/coe/indicator_coi.asp. 51. Jurkovitz CT, Li S, Norris KC, et al. Association between lack of health insurance and risk of death and ESRD: results from the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 2013;61(4 Suppl. 2):S24e32. 52. Ricardo AC, Yang W, Lora CM, et al. Limited health literacy is associated with low glomerular filtration in the Chronic Renal Insufficiency Cohort (CRIC) study. Clin Nephrol 2014;81(1): 30e7. 53. Taylor DM, Fraser S, Dudley C, Oniscu GC, Tomson C, Ravanan R, Roderick P. ATTOM investigators. Health literacy and patient outcomes in chronic kidney disease: a systematic review. Nephrol Dial Transplant 2018;33(9):1545e58. 54. Cavanaugh KL, Wingard RL, Hakim RM, et al. Low health literacy associates with increased mortality in ESRD. J Am Soc Nephrol 2010; 21(11):1979e85.

55. Cash E, Salmon P, Weissbecker I, et al. Mindfulness meditation alleviates fibromyalgia symptoms in women: results of a randomized clinical trial. Ann Behav Med 2015;49(3):319e30. 56. Healthy People - Development of the National Health Promotion and Disease Prevention Objectives for 2030 @ https://www. healthypeople.gov/2020/About-Healthy-People/DevelopmentHealthy-People-2030. 57. Kucirka LM, Grams ME, Lessler J, et al. Association of race and age with survival among patients undergoing dialysis. J Am Med Assoc 2011;306(6):620e6. 58. Yan G, Norris KC, Yu AJ, et al. The relationship of age, race, and ethnicity with survival in dialysis patients. Clin J Am Soc Nephrol 2013;8(6):953e61. 59. Kalantar-Zadeh K, Kovesdy CP, Norris KC. Racial survival paradox of dialysis patients: robust and resilient. Am J Kidney Dis 2012;60(2):182e5. 60. Rhee CM, Lertdumrongluk P, Streja E, et al. Impact of age, race and ethnicity on dialysis patient survival and kidney transplantation disparities. Am J Nephrol 2014;39(3):183e94. 61. Laster M, Norris KC. Lesson learned in mortality and kidney transplant outcomes among pediatric dialysis patients. J Am Soc Nephrol 2017;28(5):1334e6. 62. Robinson BM, Akizawa T, Jager KJ, Kerr PG, Saran R, Pisoni RL. Factors affecting outcomes in patients reaching end-stage kidney disease worldwide: differences in access to renal replacement therapy, modality use, and haemodialysis practices. Lancet 2016;388(10041):294e306. 63. Mehrotra R, Soohoo M, Rivara MB, et al. Racial and ethnic disparities in use of and outcomes with Home dialysis in the United States. J Am Soc Nephrol 2016;27(7):2123e34. 64. Saunders MR, Chin MH. Variation in dialysis quality measures by facility, neighborhood, and region. Med Care 2013;51(5):413e7. 65. Hall YN, Xu P, Chertow GM, Himmelfarb J. Characteristics and performance of minority-serving dialysis facilities. Health Serv Res 2014;49(3):971e91. 66. Chertow GM, Liu J, Monda KL, et al. Epoetin Alfa and outcomes in dialysis amid regulatory and payment reform. J Am Soc Nephrol 2016;27(10):3129e38. 67. Shen JI, Norris KC. ESRD payment reform: first do no harm. J Am Soc Nephrol 2016;27(10):2924e6. 68. Turenne MN, Cope EL, Porenta S, et al. Has dialysis payment reform led to initial racial disparities in anemia and mineral metabolism management? J Am Soc Nephrol 2015;26(3):754e64. 69. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003; 42(4 Suppl. 3):S1e201. 70. Kalantar-Zadeh K, Miller JE, Kovesdy CP, et al. Impact of race on hyperparathyroidism, mineral disarrays, administered vitamin D mimetic, and survival in hemodialysis patients. J Bone Miner Res 2010;25(12):2724e34. 71. Gupta A, Kallenbach LR, Zasuwa G, Divine GW. Race is a major determinant of secondary hyperparathyroidism in uremic patients. J Am Soc Nephrol 2000;11(2):330e4. 72. Wolf M, Betancourt J, Chang Y, et al. Impact of activated vitamin D and race on survival among hemodialysis patients. J Am Soc Nephrol 2008;19(7):1379e88. 73. Gutierrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008;359(6):584e92. 74. Wang C, Kane R, Levenson M, Kelman J, Wernecke M, Lee JY, Kozlowski S, Dekmezian C, Zhang Z, Thompson A, Smith K, Wu YT, Wei Y, Chillarige Y, Ryan Q, Worrall C, MaCurdy TE, Graham DJ. Association between changes in CMS reimbursement policy and drug labels for erythrocyte-stimulating agents with outcomes for older patients undergoing hemodialysis covered by feefor-service medicare. JAMA Intern Med 2016;176(12):1818e25.

III. EPIDEMIOLOGY

REFERENCES

75. Kinchen KS, Sadler J, Fink N, et al. The timing of specialist evaluation in chronic kidney disease and mortality. Ann Intern Med 2002; 137(6):479e86. 76. Gillespie BW, Morgenstern H, Hedgeman E, et al. Nephrology care prior to end-stage renal disease and outcomes among new ESRD patients in the USA. Clin Kidney J 2015;8(6):772e80. 77. Arora P, Obrador GT, Ruthazer R, et al. Prevalence, predictors, and consequences of late nephrology referral at a tertiary care center. J Am Soc Nephrol 1999;10(6):1281e6. 78. Prakash S, Rodriguez RA, Austin PC, et al. Racial composition of residential areas associates with access to pre-ESRD nephrology care. J Am Soc Nephrol 2010;21(7):1192e9. 79. Ifudu O, Dawood M, Iofel Y, Valcourt JS, Friedman EA. Delayed referral of black, Hispanic, and older patients with chronic renal failure. Am J Kidney Dis 1999;33(4):728e33. 80. Yan G, Cheung AK, Greene T, et al. Interstate variation in receipt of nephrologist care in US patients approaching ESRD: race, age, and state characteristics. Clin J Am Soc Nephrol 2015;10(11):1979e88. 81. Patibandla BK, Narra A, Desilva R, et al. Disparities in arteriovenous fistula placement in older hemodialysis patients. Hemodial Int 2014;18(1):118e26. 82. Hod T, Desilva RN, Patibandla BK, Vin Y, Brown RS, GoldfarbRumyantzev AS. Factors predicting failure of AV “fistula first” policy in the elderly. Hemodial Int 2014;18(2):507e15. 83. Zarkowsky DS, Arhuidese IJ, Hicks CW, Canner JK, Qazi U, Obeid T, Schneider E, Abularrage CJ, Freischlag JA, Malas MB. Racial/ethnic disparities associated with initial hemodialysis access. JAMA Surg 2015;150(6):529e36. 84. Norton JM, Moxey-Mims MM, Eggers PW, et al. Social determinants of racial disparities in CKD. J Am Soc Nephrol 2016;27(9):2576e95. 85. Kalantar-Zadeh K, Kovesdy CP, Derose SF, Horwich TB, Fonarow GC. Racial and survival paradoxes in chronic kidney disease. Nat Clin Pract Nephrol 2007;3(9):493e506.

119

86. Kalantar-Zadeh K, Golan E, Shohat T, Streja E, Norris KC, Kopple JD. Survival disparities within American and Israeli dialysis populations: learning from similarities and distinctions across race and ethnicity. Semin Dial 2010;23(6):586e94. 87. Rhee CM, Kalantar-Zadeh K, Norris KC. Why minorities live longer on dialysis: an in-depth examination of the Danish nephrology registry. Nephrol Dial Transplant 2016;31(7):1027e30. 88. van den Beukel TO, Hommel K, Kamper AL, et al. Differences in survival on chronic dialysis treatment between ethnic groups in Denmark: a population-wide, national cohort study. Nephrol Dial Transplant 2016;31(7):1160e7. 89. Arce CM, Goldstein BA, Mitani AA, Winkelmayer WC. Trends in relative mortality between Hispanic and non-Hispanic whites initiating dialysis: a retrospective study of the US Renal Data System. Am J Kidney Dis 2013;62(2):312e21. 90. Pei YP, Greenwood CM, Chery AL, Wu GG. Racial differences in survival of patients on dialysis. Kidney Int 2000;58(3):1293e9. 91. Wong JS, Port FK, Hulbert-Shearon TE, et al. Survival advantage in Asian American end-stage renal disease patients. Kidney Int 1999; 55(6):2515e23. 92. Zhang Y. The association between dialysis facility quality and facility characteristics, neighborhood demographics, and region. Am J Med Qual 2016;31(4):358e63. 93. Norris KC. On Race and Medicine: until health care becomes truly personalized, race and ethnicity will continue to be important clues guiding medical treatments. Scientist Febuary 2014;28(2). http:// www.the-scientist.com/?articles.view/articleNo/38950/title/OnRace-and-Medicine/. 94. Williams AW. Health policy, disparities, and the kidney. Adv Chron Kidney Dis 2015;22(1):54e9. 95. Norris KC, Williams SF, Rhee CM, et al. Hemodialysis disparities in African Americans: the deeply integrated concept of race in the social fabric of our society. Semin Dial 2017;30(3):213e23.

III. EPIDEMIOLOGY