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The Epidemiology of End-Stage Renal Disease among African Americans
The Epidemiology of End-Stage Renal Disease among African Americans D. MARTINS, MD; N. TAREEN, MD; K. C. NORRIS, MD
ABSTRACT: Although disparities in outcomes among African Americans compared with whites with respect to cardiovascular disease, cancer, diabetes, infant mortality, and other health standards have been well-described, these disparities are most dramatic with respect to kidney diseases. End-stage renal disease (ESRD) occurs almost 4 times more commonly in African Americans than in their white counterparts. These disparate rates of kidney disease may be caused by the complex interplay of genetic, environmental, cultural, and socioeconomic factors. African Americans are particularly vulnerable to the deleterious renal effects of hypertension and may require more aggressive blood pressure control than whites to accrue benefit with respect to preservation of renal function. Diabetes, the leading cause of ESRD in the United States, is another important
factor in the excess renal morbidity and mortality of African Americans because of its prevalence in this population. Other renal diseases, especially those associated with HIV/AIDS, are also much more likely to affect African Americans than other American population subgroups. A more thorough understanding of the epidemiology of renal diseases in African Americans and the cultural, social, and biological differences that underlie racial disparities in prevalence of renal disease will be essential to the design of effective public health strategies for prevention and treatment of this burdensome problem. KEY INDEXING TERMS: Epidemiology; Renal disease; End-stage renal disease (ESRD); African Americans; Hypertension; Diabetes. [Am J Med Sci 2002;323(2):65–71.]
T
African Americans than among their white counterparts and continues to represent 1 of the most dramatic examples of health disparity in our nation (Figure 1). Presently, more than 350,000 Americans receive renal replacement therapy for ESRD.4 Moreover, it is not generally appreciated that more than 10 million Americans may have chronic kidney disease.5 With an incidence of more than 950 cases per million, African Americans suffer 1 of the highest (if not the highest) rates of treated ESRD in the world.4 The reasons for this disparity seem to be multifactorial. This report discusses the epidemiology and some of the key factors that contribute to the development of chronic kidney disease, and ESRD in particular, among African Americans.
he 1984 Secretary of Health’s Task Force Report on “Black and Minority Health” highlighted the principal causes for the 86.1% “excess deaths” in blacks, Hispanics, Asian/Pacific Islanders, and Native Americans. They were cardiovascular (and related) diseases, diabetes, cancer, accidents and intentional injuries, digestive diseases, infant mortality, HIV/AIDS, and substance use/abuse. By then, several reports had already noted that the incidence of end-stage renal disease (ESRD) was several-fold higher among African Americans than whites.1,2 In 1998, these disparities remained essentially unchanged, prompting President Clinton to enact the “Racial and Ethnic Health Disparities Initiative,” which declares these disparities to be unacceptable in a country that values equality and equal opportunity.3 Recent data indicate treated ESRD occurs nearly 4 times more frequently among From the Department of Internal Medicine, Charles R. Drew University, Los Angeles, California (DM, NT, KCN), the Department of Internal Medicine, UCLA School of Medicine, Los Angeles, California (KCN), and the West Los Angeles Veterans Administration Medical Center (NT). This research was supported in part by National Institutes of Health/Research Centers in Minority Institutions grants P20RR11145 and G12-RR03026. Correspondence: Keith C. Norris, M.D., Department of Internal Medicine, Charles R. Drew University of Medicine and Science, 12021 S. Wilmington Ave, Los Angeles, CA 90059. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Chronic Kidney Disease The disproportionately high rates of ESRD among African Americans suggest that similar findings might exist for chronic kidney disease. An analysis of more than 18,000 participants aged 12 and above evaluated in the National Health and Nutrition Survey III (NHANES III) noted a prevalence of elevated serum creatinine levels nearly 3 times higher (ⱖ 2.0 mg/dL) among African Americans than their white counterparts.5 It is unclear to what extent race as an independent factor accounts for the greater prevalence of elevated serum creatinine values among 65
End-Stage Renal Disease among African Americans
Figure 1. Overall ESRD incidence rate by race and ethnicity (1999; per million, adjusted for age and gender).
African Americans or acts as a surrogate for insurance status, family income, and education.6 The reason for a more rapid entry of African Americans into the ESRD system seems to be related to suboptimal medical care (lesser control of underlying medical conditions, limited access to care), cultural (delayed presentation and diagnosis, diet, health care beliefs, etc.), or other factors, including environmental exposures and/or genetic predisposition.
Figure 3. Mean age at start of ESRD therapy by race (1990 –1999).
second highest rate of diabetes-related ESRD, second only to Native Americans (Figure 6). By contrast, African Americans have the highest rate of hypertension-related ESRD, far exceeding that of any other racial or ethnic group (Figure 6). Hypertension remains a close second to DM as the leading
Overall ESRD There are multiple causes of renal disease. An in-depth understanding of renal disease in each of these many causes may provide greater insight into the pathophysiology and advance therapeutic options/strategies for all forms of renal diseases. Although the overall incidence of ESRD has continued to rise over the last decade, the magnitude of racial disparities has remained relatively unchanged (Figure 2). Among African Americans, ESRD occurs at a younger age (Figure 3), and the incidence rates are greater at each decade of life (Figure 4). Diabetes mellitus (DM) is the leading cause of ESRD for all Americans, accounting for nearly 45% of new cases each year (Figure 5). African Americans have the
Figure 2. ESRD incidence by race, 1990 –1999 (USRDS 2000).
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Figure 4. 1998 ESRD incidence rate by age and race (per million, adjusted for gender).
Figure 5. Percentage ESRD incidence by primary diagnosis, 1999. Other, cystic kidney disease, other urologic, and other causes; missing, unknown and missing causes.
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Figure 6. DM and hypertension ESRD incidence rates by race/ ethnicity (1999; per million, adjusted for age and gender).
cause of ESRD in the African American community, and emerging data suggest appropriate therapy can halt or delay the progression of renal impairment from each of these disorders.4,7–9 Although the rates of ESRD related to glomerular disease, obstructive disease, and cystic kidney disease are more similar among racial/ethnic groups, African Americans still have modestly higher rates of ESRD from these disorders as well (Figure 7). Human immunodeficiency virus (HIV) nephropathy, a more recently described entity, is not nearly as common; its incidence is rising, however, and it seems to be as much as 10 times more common among African Americans.10 A greater awareness of key medical conditions as a cause of ESRD among African Americans may improve screening strategies and the early implementation of potential renal-protective strategies for “at-risk” patients. DM and DM-Related ESRD Diabetes affects African American men at a rate nearly 50% greater than that of whites; for African American women, the rate is nearly 100% greater.
Figure 7. Glomerulonephritis and cystic kidney disease ESRD incidence rates by race/ethnicity (1999; per million, adjusted for age and gender).
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Moreover, diabetes affects Hispanics (1.9 times that of non-Hispanic whites) and Native American Indians (2.8 times that of non-Hispanic whites) at an even higher rate.11,12 Diabetes is associated with an accelerated progression of vascular disease and a substantially increased risk of renal failure. The Diabetes Control and Complications Trial (DCCT) demonstrated that tight glucose control can reduce the incidence of diabetes-related vascular complications, consistent with a biologic effect of the altered metabolic milieu in diabetes as critical in the development of vascular disease.13,14 However, the DCCT was a highly selective study group with low minority participation. It is unlikely that intensive therapy can be delivered to lower socioeconomic and less well-educated populations, many of whom are racial/ethnic minorities, due to costs of therapy and the risks of inducing deleterious side-effects such as symptomatic hypoglycemia.15–17 The United Kingdom Prospective Diabetes Study also demonstrated the salutary effects of tight glucose control.18 Importantly, this study and several others have shown that blood pressure control in patients with diabetes is critical in reducing the progression of renal impairment. Both the level of blood pressure control and the class of antihypertensive therapy have been suggested to have independent protective effects. However, the role of class-specific antihypertensive therapy remains more controversial. Although much of the emerging literature suggests that the interruption of the renin-angiotensin system confers additional protection beyond blood pressure control,8,19 –21 achieving target levels of blood pressure seems to be the most important factor.18,22–24 Despite improvements in our overall understanding of DM, diabetic nephropathy now accounts for nearly one half of new ESRD cases; more than 75% of these cases are due to type 2 diabetes. The adjusted incidence rate of diabetes is now nearly 75% greater than that of hypertension, the second leading cause of ESRD (Figure 8). In contrast, only 10 years ago, the rate of DM-related ESRD did not differ from that of hypertension-related ESRD (Figures 8 –10). The dramatic increase in DM-related ESRD in contrast to hypertension and other causes is multifactorial and may reflect such factors as the rapid rise of DM in our country, changes in patterns of clinical diagnosis, and/or variations in relative effectiveness of disease specific medical treatments. The adjusted treated incidence rate (1996 –1999) of DM as a primary ESRD diagnosis is 407 per million for African Americans versus 95 per million for whites. Asians have an intermediate rate of 182 per million and Native Americans have the highest rate at an alarming 520 per million population (Figure 6). 67
End-Stage Renal Disease among African Americans
Figure 8. ESRD incidence rates by primary diagnosis (1999; per million, adjusted for age, gender, ethnicity, and race). HTN, hypertension; GN, glomerulonephritis; Other, cystic kidney disease, other urologic, and other causes; missing and unknown causes are excluded.
Hypertension and Hypertension-Related ESRD Hypertension is an important risk factor not only for renal failure but also for the spectrum of cardiovascular and cardiovascular-related diseases including heart attack, stroke, congestive heart failure, and peripheral vascular disease.25–29 African Americans have a 50 to 75% higher prevalence of hypertension compared with other Americans and 2 to 3 times greater prevalence of stage 2 and 3 hypertension, levels of blood pressure control more likely to progress to ESRD.30 A recent analysis of more than 16,000 adults (ⱖ17 years of age) who participated in the NHANES III survey noted an elevated serum creatinine level was strongly related to inadequate treatment of high blood pressure.31 A report from the Multiple Risk Factors Intervention Trial (MRFIT) noted that despite similar targets for control of blood pressure (diastolic pressure ⬍ 95 mm Hg), renal function declined 5 times faster in hypertensive African American subjects than in non-African
Figure 9. ESRD incidence rates by primary diagnosis (1990 – 1999; per million, adjusted for age, gender, ethnicity, and race). Other, cystic kidney disease, other urologic, and other causes; missing and unknown causes are excluded.
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Americans.32 The Modification of Diet in Renal Disease Study found that improved blood pressure control slowed the decline in glomerular filtration rate in both black and white patients with proteinuria. However, among African Americans, this effect occurred only when there was a lowering of the mean arterial pressure to a level of ⱕ98 mm Hg, compared with a blood pressure level of ⱕ107 mmHg for white subjects.33 These results suggest a lower level of blood pressure may be necessary to prevent progressive renal disease for African American patients with chronic kidney disease and hypertension. The incidence of hypertension-related ESRD is highly disproportionate among Americans, with the overall rate among African Americans 5 times that in whites; for 20- to 44-year-old African American males, the rate is nearly 20 times that of whites.4 Several studies,30,34 –36 but not all,37,38 have suggested that African Americans have a racial predisposition to developing hypertension-related renal failure independent of other risk factors. The role of hypertension as a common cause for ESRD or as a secondary manifestation of some other primary renal damage remains a subject of intense debate. The ESRD database is generated primarily on clinical grounds and may not represent the actual ESRD diagnosis. A recent report from Fernandes et al39 suggests that in England, hypertensive nephrosclerosis in blacks may be overestimated by nearly 50%. Perneger et al40 reported that, given a similar clinical presentation, nephrologists were more likely to diagnose hypertension as a cause of renal failure if the patient was African American.40 In contrast, data from the African American Study of Hypertension and Kidney Disease pilot study demonstrated a close correlation (⬎95%) between biopsy findings and a well defined clinical picture of hypertensive nephrosclerosis.41 In either case, the powerful association of hypertension as the primary cause or an early manifestation indicating a high-risk situation remains a clinically relevant tool. In the United States, hypertension as a reported primary cause for renal disease now accounts for 33.4% of new ESRD cases among African Americans, a close second to 43.7% for diabetes.4 Until 1995, hypertension was the leading cause of ESRD within the African American community. Among whites hypertension accounts for only 24% of cases, Asians 23% and Native Americans only 12%.4 The incidence rate (1996 –1999) of hypertension as a primary ESRD diagnosis is 319 per million for African Americans versus 52 per million for whites, 100 per million for Asians, and 91 per million for Native Americans (Figure 6). HIV- or AIDS-Related Nephropathy Although most of the other less common causes of ESRD, such as glomerulonephritis, obstructive February 2002 Volume 323 Number 2
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Figure 10. Diabetes and hypertension ESRD incidence rates by race (1982–1999; per million, adjusted for age and gender).
uropathy and PCKD are relatively similar among racial/ethnic groups, HIV/AIDS-related nephropathy stands out as another unique category with a dramatically greater incidence among African Americans. This disease is histopathologically distinct from the nephropathy of intravenous drug abuse (heroin nephropathy) and subsequent development of ESRD.42 Klotman and colleagues10,42,43 have reported HIV/AIDS-associated nephropathy occurring more than 10 times more commonly among African Americans than among whites. Indeed, HIV/AIDS-associated nephropathy is now the third leading cause of ESRD among 20- to 64-yearold African Americans.10 Among patients diagnosed with ESRD secondary to HIV AIDS nephropathy from 1990 to 1998, 88% were black (Table 1). Although the number of new cases has fallen since 1996, probably because of improved antiretroviral therapy, the number of “at-risk” HIV/AIDS patients continues to rise, and continued surveillance is critical to detect a potential resurgence of HIV/AIDSrelated nephropathy over time. Although HIV/AIDS associated disparities in ESRD remain poorly understood, a familial clustering of ESRD among African Americans was recently reported for family members of HIV/AIDS-associated ESRD patients compared with family members of persons infected with HIV with chronic kidney disease but without ESRD.44 The authors hypothesize a familial predisposition for ESRD exists independent of HIV but Table 1. Incidence of AIDS Nephropathy Cases by Race/Ethnicity Year
Black
White
Other
Total
1990 1991 1992 1993 1994 1995 1996 1997 1998
159 277 351 441 515 844 732 744 721
8 18 24 30 63 63 81 60 63
1 4 2 7 24 33 39 22 32
168 299 377 478 602 940 852 826 816
Modified from reference 10.
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places persons infected with HIV from “at-risk” families at greater risk for subsequent development of ESRD. Summary African Americans continue to suffer from disproportionately high rates of ESRD. Diabetes and hypertension are the leading causes of ESRD across racial/ethnic lines and are responsible for more than 70% of patients entering the ESRD program. The higher prevalence of diabetes and hypertension among African Americans accounts, in part, for the greater incidence of ESRD. Although race has been proposed as an independent biologic variable accounting for the disproportionately high rate of renal failure among African American patients, factors such as access to care, insurance status, education, family income, and others have been associated with an increased risk of renal disease.6,26,28,30,32–38 At present, limitations in the science of medicine juxtaposed on a unique race/class structure in our society does not allow an adequate assessment of the many cultural, environmental, psychosocial, health care access, and related factors impacting an individual patient for whom their race/ ethnicity may only be a surrogate. Despite these limitations, racial/ethnic clustering does occur in ESRD and a comprehensive understanding of epidemiological variations in ESRD provide a foundation for the development of effective public health strategies including education, screening, prevention, and early treatment of renal disease. Such interventions will hopefully attenuate the progressive rise in number of persons needing renal replacement therapy across our nation. References 1. Easterling RE. Racial factors in the incidence and causation of end stage renal disease. Trans Am Soc Artif Intern Organs 1977;23:28 –32. 2. Rostand SG, Kirk KA, Rutsky EA, et al. Racial differences in the incidence of treatment for end-stage renal disease. N Engl J Med 1982;306:1276 –9.
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End-Stage Renal Disease among African Americans
3. President Clinton Announces New Racial and Ethnic Health Disparities Initiative. 1998. Available at: URL: http://raceandhealth.hhs.gov/sidebars/report.htm. 4. U.S. Renal Data System. USRDS 2001 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2001. Available at: URL: http://www. usrds.org/atlas.htm. 5. Jones CA, McQuillan GM, Kusek JW, et al. Serum creatinine levels in the US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 1998;32: 992–9. 6. Norris KC, Pan D, Owen WF. Risk factors for early renal disease in special populations [abstract]. Ethn Dis 2000;10: 310. 7. Agodoa LY, Appel L, Bakris GL, et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001;285:2719 –28. 8. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456 – 62. 9. Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996;334:939 – 45. 10. Monahan M, Tanji N, Klotman PE. HIV-associated nephropathy: An urban epidemic. Semin Nephrol 2001;21:393– 402. 11. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988 –1994. Diabetes Care 1998; 21:518 –24. 12. National Diabetes Fact Sheet: Incidence of diabetes. Available at: URL: http://www.cdc.gov/diabetes/pubs/facts98. htm#incidence. 13. Molyneaux LM, Constantino MI, McGill M, et al. Better glycaemic control and risk reduction of diabetic complications in Type 2 diabetes: comparison with the DCCT. Diabetes Res Clin Pract 1998;42:77– 83. 14. Anonymous. Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group. Kidney Int 1995;47: 1703–20. 15. Herman WH, Eastman RC. The effects of treatment on the direct costs of diabetes. Diabetes Care 1998;21(Suppl 3):C19 – 24. 16. Egger M, Davey Smith G, Stettler C, et al. Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis. Diabet Med 1997;14:919 –28. 17. Gautier JF, Beressi JP, Leblanc H, et al. Are the implications of the Diabetes Control and Complications Trial (DCCT) feasible in daily clinical practice? Diabetes Metab 1996;22:415–9. 18. Anonymous. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703–13. 19. Anonymous. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000;355:253–9.
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20. Jerums G, Allen TJ, Campbell DJ, et al. Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria. Am J Kidney Dis, 2001;37:890 –9. 21. Anonymous. Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data. Ann Intern Med 2001;134:370 –9. 22. Bakris GL, Copley JB, Vicknair N, et al. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int 1996;50: 1641–50. 23. Lievre M, Gueyffier F, Ekbom T, et al. Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis. The INDANA Steering Committee. Diabetes Care 2000;23(Suppl 2):B65–71. 24. Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis 2000;36:646 – 61. 25. Hennekens CH. Lessons from hypertension trials. Am J Med 1998;104(6A):50S–53S. 26. Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996;334: 13– 8. 27. Deubner DC, Tyroler HA, Cassel JC, et al. Attributable risk, population attributable risk and population attributable fraction of death associated with hypertension in a biracial population. Circulation 1975;52:901– 8. 28. Norris KC, Francis CK. Gender and ethnic differences and considerations in cardiovascular risk assessment and prevention in African-Americans. In: Wong N, Gardin JM, Black HR. Preventive Cardiology. New York: McGraw-Hill; 2000. p. 459 – 484. 29. Anonymous. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413– 46. 30. Klag MJ, Stamler J, Brancati FL, et al. End-stage renal disease in African-American and white men: 16-year MRFIT findings. JAMA 1997;277:1293– 8. 31. Coresh J, Wei GL, McQuillan G, et al. Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med 2001;161:1207–16. 32. Walker WG, Neaton JD, Cutler JA, et al. Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. JAMA 1992;268:3085–91. 33. Hebert LA, Kusek JW, Greene T, et al. Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group. Hypertension 1997;30:428 –35. 34. Rosansky SJ, Hoover DR, King L, et al. The association of blood pressure levels and change in renal function in hypertensive and nonhypertensive subjects. Arch Intern Med 1990; 150:2073– 6. 35. Rostand SG, Brown G, Kirk KA, et al. Renal insufficiency in treated essential hypertension. N Engl J Med 1989;320: 684 – 8. 36. McClellan W, Tuttle E, Issa A. Racial differences in the incidence of end-stage renal disease (ESRD) are not entirely explained by differences in the prevalence of hypertension. Am J Kidney Dis 1988;12:285–90.
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37. Pettinger WA, Lee HC, Reisch J, et al. Long-term improvement in renal function after short-term strict blood pressure control in hypertensive nephrosclerosis. Hypertension 1989;13:766 –72. 38. Toto R, Mitchell H, Smith RD, et al. Strict blood pressure control and progression of renal disease in hypertensive nephropathy. Kidney Int 1995;48:851–9. 39. Fernandes PF, Ellis PA, Roderick PJ, et al. Causes of End-Stage Renal Failure in Black Patients Starting Renal Replacement Therapy. Am J Kidney Dis 2000;36:301–9. 40. Perneger TV, Rossiter KA, Klag MJ, et al. Diagnosis of hypertensive end-stage renal disease: effect of patient’s race. Am J Epidemiol 1995;141:10 –5.
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41. Fogo A, Breyer JA, Smith MC, et al. Accuracy of the diagnosis of hypertensive nephrosclerosis in African-Americans: a report from the African-American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators. Kidney Int 1997;51:244 –52. 42. Klotman PE. HIV-associated nephropathy. Kidney Int 1999; 56:1161–76. 43. Winston JS, Burns GC, Klotman PE. The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy. Semin Nephrol 1998;18:373–7. 44. Freedman BI, Soucie MJ, Stone SM, et al. Familial clustering of end-stage renal disease in blacks with HIV-associated nephropathy. Am J Kidney Dis 1999;34:254 – 8.
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ABSTRACT: Although disparities in outcomes among African Americans compared with whites with respect to cardiovascular disease, cancer, diabetes, infant mortality, and other health standards have been well-described, these disparities are most dramatic with respect to kidney diseases. End-stage renal disease (ESRD) occurs almost 4 times more commonly in African Americans than in their white counterparts. These disparate rates of kidney disease may be caused by the complex interplay of genetic, environmental, cultural, and socioeconomic factors. African Americans are particularly vulnerable to the deleterious renal effects of hypertension and may require more aggressive blood pressure control than whites to accrue benefit with respect to preservation of renal function. Diabetes, the leading cause of ESRD in the United States, is another important
factor in the excess renal morbidity and mortality of African Americans because of its prevalence in this population. Other renal diseases, especially those associated with HIV/AIDS, are also much more likely to affect African Americans than other American population subgroups. A more thorough understanding of the epidemiology of renal diseases in African Americans and the cultural, social, and biological differences that underlie racial disparities in prevalence of renal disease will be essential to the design of effective public health strategies for prevention and treatment of this burdensome problem. KEY INDEXING TERMS: Epidemiology; Renal disease; End-stage renal disease (ESRD); African Americans; Hypertension; Diabetes. [Am J Med Sci 2002;323(2):65–71.]
T
African Americans than among their white counterparts and continues to represent 1 of the most dramatic examples of health disparity in our nation (Figure 1). Presently, more than 350,000 Americans receive renal replacement therapy for ESRD.4 Moreover, it is not generally appreciated that more than 10 million Americans may have chronic kidney disease.5 With an incidence of more than 950 cases per million, African Americans suffer 1 of the highest (if not the highest) rates of treated ESRD in the world.4 The reasons for this disparity seem to be multifactorial. This report discusses the epidemiology and some of the key factors that contribute to the development of chronic kidney disease, and ESRD in particular, among African Americans.
he 1984 Secretary of Health’s Task Force Report on “Black and Minority Health” highlighted the principal causes for the 86.1% “excess deaths” in blacks, Hispanics, Asian/Pacific Islanders, and Native Americans. They were cardiovascular (and related) diseases, diabetes, cancer, accidents and intentional injuries, digestive diseases, infant mortality, HIV/AIDS, and substance use/abuse. By then, several reports had already noted that the incidence of end-stage renal disease (ESRD) was several-fold higher among African Americans than whites.1,2 In 1998, these disparities remained essentially unchanged, prompting President Clinton to enact the “Racial and Ethnic Health Disparities Initiative,” which declares these disparities to be unacceptable in a country that values equality and equal opportunity.3 Recent data indicate treated ESRD occurs nearly 4 times more frequently among From the Department of Internal Medicine, Charles R. Drew University, Los Angeles, California (DM, NT, KCN), the Department of Internal Medicine, UCLA School of Medicine, Los Angeles, California (KCN), and the West Los Angeles Veterans Administration Medical Center (NT). This research was supported in part by National Institutes of Health/Research Centers in Minority Institutions grants P20RR11145 and G12-RR03026. Correspondence: Keith C. Norris, M.D., Department of Internal Medicine, Charles R. Drew University of Medicine and Science, 12021 S. Wilmington Ave, Los Angeles, CA 90059. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Chronic Kidney Disease The disproportionately high rates of ESRD among African Americans suggest that similar findings might exist for chronic kidney disease. An analysis of more than 18,000 participants aged 12 and above evaluated in the National Health and Nutrition Survey III (NHANES III) noted a prevalence of elevated serum creatinine levels nearly 3 times higher (ⱖ 2.0 mg/dL) among African Americans than their white counterparts.5 It is unclear to what extent race as an independent factor accounts for the greater prevalence of elevated serum creatinine values among 65
End-Stage Renal Disease among African Americans
Figure 1. Overall ESRD incidence rate by race and ethnicity (1999; per million, adjusted for age and gender).
African Americans or acts as a surrogate for insurance status, family income, and education.6 The reason for a more rapid entry of African Americans into the ESRD system seems to be related to suboptimal medical care (lesser control of underlying medical conditions, limited access to care), cultural (delayed presentation and diagnosis, diet, health care beliefs, etc.), or other factors, including environmental exposures and/or genetic predisposition.
Figure 3. Mean age at start of ESRD therapy by race (1990 –1999).
second highest rate of diabetes-related ESRD, second only to Native Americans (Figure 6). By contrast, African Americans have the highest rate of hypertension-related ESRD, far exceeding that of any other racial or ethnic group (Figure 6). Hypertension remains a close second to DM as the leading
Overall ESRD There are multiple causes of renal disease. An in-depth understanding of renal disease in each of these many causes may provide greater insight into the pathophysiology and advance therapeutic options/strategies for all forms of renal diseases. Although the overall incidence of ESRD has continued to rise over the last decade, the magnitude of racial disparities has remained relatively unchanged (Figure 2). Among African Americans, ESRD occurs at a younger age (Figure 3), and the incidence rates are greater at each decade of life (Figure 4). Diabetes mellitus (DM) is the leading cause of ESRD for all Americans, accounting for nearly 45% of new cases each year (Figure 5). African Americans have the
Figure 2. ESRD incidence by race, 1990 –1999 (USRDS 2000).
66
Figure 4. 1998 ESRD incidence rate by age and race (per million, adjusted for gender).
Figure 5. Percentage ESRD incidence by primary diagnosis, 1999. Other, cystic kidney disease, other urologic, and other causes; missing, unknown and missing causes.
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Figure 6. DM and hypertension ESRD incidence rates by race/ ethnicity (1999; per million, adjusted for age and gender).
cause of ESRD in the African American community, and emerging data suggest appropriate therapy can halt or delay the progression of renal impairment from each of these disorders.4,7–9 Although the rates of ESRD related to glomerular disease, obstructive disease, and cystic kidney disease are more similar among racial/ethnic groups, African Americans still have modestly higher rates of ESRD from these disorders as well (Figure 7). Human immunodeficiency virus (HIV) nephropathy, a more recently described entity, is not nearly as common; its incidence is rising, however, and it seems to be as much as 10 times more common among African Americans.10 A greater awareness of key medical conditions as a cause of ESRD among African Americans may improve screening strategies and the early implementation of potential renal-protective strategies for “at-risk” patients. DM and DM-Related ESRD Diabetes affects African American men at a rate nearly 50% greater than that of whites; for African American women, the rate is nearly 100% greater.
Figure 7. Glomerulonephritis and cystic kidney disease ESRD incidence rates by race/ethnicity (1999; per million, adjusted for age and gender).
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Moreover, diabetes affects Hispanics (1.9 times that of non-Hispanic whites) and Native American Indians (2.8 times that of non-Hispanic whites) at an even higher rate.11,12 Diabetes is associated with an accelerated progression of vascular disease and a substantially increased risk of renal failure. The Diabetes Control and Complications Trial (DCCT) demonstrated that tight glucose control can reduce the incidence of diabetes-related vascular complications, consistent with a biologic effect of the altered metabolic milieu in diabetes as critical in the development of vascular disease.13,14 However, the DCCT was a highly selective study group with low minority participation. It is unlikely that intensive therapy can be delivered to lower socioeconomic and less well-educated populations, many of whom are racial/ethnic minorities, due to costs of therapy and the risks of inducing deleterious side-effects such as symptomatic hypoglycemia.15–17 The United Kingdom Prospective Diabetes Study also demonstrated the salutary effects of tight glucose control.18 Importantly, this study and several others have shown that blood pressure control in patients with diabetes is critical in reducing the progression of renal impairment. Both the level of blood pressure control and the class of antihypertensive therapy have been suggested to have independent protective effects. However, the role of class-specific antihypertensive therapy remains more controversial. Although much of the emerging literature suggests that the interruption of the renin-angiotensin system confers additional protection beyond blood pressure control,8,19 –21 achieving target levels of blood pressure seems to be the most important factor.18,22–24 Despite improvements in our overall understanding of DM, diabetic nephropathy now accounts for nearly one half of new ESRD cases; more than 75% of these cases are due to type 2 diabetes. The adjusted incidence rate of diabetes is now nearly 75% greater than that of hypertension, the second leading cause of ESRD (Figure 8). In contrast, only 10 years ago, the rate of DM-related ESRD did not differ from that of hypertension-related ESRD (Figures 8 –10). The dramatic increase in DM-related ESRD in contrast to hypertension and other causes is multifactorial and may reflect such factors as the rapid rise of DM in our country, changes in patterns of clinical diagnosis, and/or variations in relative effectiveness of disease specific medical treatments. The adjusted treated incidence rate (1996 –1999) of DM as a primary ESRD diagnosis is 407 per million for African Americans versus 95 per million for whites. Asians have an intermediate rate of 182 per million and Native Americans have the highest rate at an alarming 520 per million population (Figure 6). 67
End-Stage Renal Disease among African Americans
Figure 8. ESRD incidence rates by primary diagnosis (1999; per million, adjusted for age, gender, ethnicity, and race). HTN, hypertension; GN, glomerulonephritis; Other, cystic kidney disease, other urologic, and other causes; missing and unknown causes are excluded.
Hypertension and Hypertension-Related ESRD Hypertension is an important risk factor not only for renal failure but also for the spectrum of cardiovascular and cardiovascular-related diseases including heart attack, stroke, congestive heart failure, and peripheral vascular disease.25–29 African Americans have a 50 to 75% higher prevalence of hypertension compared with other Americans and 2 to 3 times greater prevalence of stage 2 and 3 hypertension, levels of blood pressure control more likely to progress to ESRD.30 A recent analysis of more than 16,000 adults (ⱖ17 years of age) who participated in the NHANES III survey noted an elevated serum creatinine level was strongly related to inadequate treatment of high blood pressure.31 A report from the Multiple Risk Factors Intervention Trial (MRFIT) noted that despite similar targets for control of blood pressure (diastolic pressure ⬍ 95 mm Hg), renal function declined 5 times faster in hypertensive African American subjects than in non-African
Figure 9. ESRD incidence rates by primary diagnosis (1990 – 1999; per million, adjusted for age, gender, ethnicity, and race). Other, cystic kidney disease, other urologic, and other causes; missing and unknown causes are excluded.
68
Americans.32 The Modification of Diet in Renal Disease Study found that improved blood pressure control slowed the decline in glomerular filtration rate in both black and white patients with proteinuria. However, among African Americans, this effect occurred only when there was a lowering of the mean arterial pressure to a level of ⱕ98 mm Hg, compared with a blood pressure level of ⱕ107 mmHg for white subjects.33 These results suggest a lower level of blood pressure may be necessary to prevent progressive renal disease for African American patients with chronic kidney disease and hypertension. The incidence of hypertension-related ESRD is highly disproportionate among Americans, with the overall rate among African Americans 5 times that in whites; for 20- to 44-year-old African American males, the rate is nearly 20 times that of whites.4 Several studies,30,34 –36 but not all,37,38 have suggested that African Americans have a racial predisposition to developing hypertension-related renal failure independent of other risk factors. The role of hypertension as a common cause for ESRD or as a secondary manifestation of some other primary renal damage remains a subject of intense debate. The ESRD database is generated primarily on clinical grounds and may not represent the actual ESRD diagnosis. A recent report from Fernandes et al39 suggests that in England, hypertensive nephrosclerosis in blacks may be overestimated by nearly 50%. Perneger et al40 reported that, given a similar clinical presentation, nephrologists were more likely to diagnose hypertension as a cause of renal failure if the patient was African American.40 In contrast, data from the African American Study of Hypertension and Kidney Disease pilot study demonstrated a close correlation (⬎95%) between biopsy findings and a well defined clinical picture of hypertensive nephrosclerosis.41 In either case, the powerful association of hypertension as the primary cause or an early manifestation indicating a high-risk situation remains a clinically relevant tool. In the United States, hypertension as a reported primary cause for renal disease now accounts for 33.4% of new ESRD cases among African Americans, a close second to 43.7% for diabetes.4 Until 1995, hypertension was the leading cause of ESRD within the African American community. Among whites hypertension accounts for only 24% of cases, Asians 23% and Native Americans only 12%.4 The incidence rate (1996 –1999) of hypertension as a primary ESRD diagnosis is 319 per million for African Americans versus 52 per million for whites, 100 per million for Asians, and 91 per million for Native Americans (Figure 6). HIV- or AIDS-Related Nephropathy Although most of the other less common causes of ESRD, such as glomerulonephritis, obstructive February 2002 Volume 323 Number 2
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Figure 10. Diabetes and hypertension ESRD incidence rates by race (1982–1999; per million, adjusted for age and gender).
uropathy and PCKD are relatively similar among racial/ethnic groups, HIV/AIDS-related nephropathy stands out as another unique category with a dramatically greater incidence among African Americans. This disease is histopathologically distinct from the nephropathy of intravenous drug abuse (heroin nephropathy) and subsequent development of ESRD.42 Klotman and colleagues10,42,43 have reported HIV/AIDS-associated nephropathy occurring more than 10 times more commonly among African Americans than among whites. Indeed, HIV/AIDS-associated nephropathy is now the third leading cause of ESRD among 20- to 64-yearold African Americans.10 Among patients diagnosed with ESRD secondary to HIV AIDS nephropathy from 1990 to 1998, 88% were black (Table 1). Although the number of new cases has fallen since 1996, probably because of improved antiretroviral therapy, the number of “at-risk” HIV/AIDS patients continues to rise, and continued surveillance is critical to detect a potential resurgence of HIV/AIDSrelated nephropathy over time. Although HIV/AIDS associated disparities in ESRD remain poorly understood, a familial clustering of ESRD among African Americans was recently reported for family members of HIV/AIDS-associated ESRD patients compared with family members of persons infected with HIV with chronic kidney disease but without ESRD.44 The authors hypothesize a familial predisposition for ESRD exists independent of HIV but Table 1. Incidence of AIDS Nephropathy Cases by Race/Ethnicity Year
Black
White
Other
Total
1990 1991 1992 1993 1994 1995 1996 1997 1998
159 277 351 441 515 844 732 744 721
8 18 24 30 63 63 81 60 63
1 4 2 7 24 33 39 22 32
168 299 377 478 602 940 852 826 816
Modified from reference 10.
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places persons infected with HIV from “at-risk” families at greater risk for subsequent development of ESRD. Summary African Americans continue to suffer from disproportionately high rates of ESRD. Diabetes and hypertension are the leading causes of ESRD across racial/ethnic lines and are responsible for more than 70% of patients entering the ESRD program. The higher prevalence of diabetes and hypertension among African Americans accounts, in part, for the greater incidence of ESRD. Although race has been proposed as an independent biologic variable accounting for the disproportionately high rate of renal failure among African American patients, factors such as access to care, insurance status, education, family income, and others have been associated with an increased risk of renal disease.6,26,28,30,32–38 At present, limitations in the science of medicine juxtaposed on a unique race/class structure in our society does not allow an adequate assessment of the many cultural, environmental, psychosocial, health care access, and related factors impacting an individual patient for whom their race/ ethnicity may only be a surrogate. Despite these limitations, racial/ethnic clustering does occur in ESRD and a comprehensive understanding of epidemiological variations in ESRD provide a foundation for the development of effective public health strategies including education, screening, prevention, and early treatment of renal disease. Such interventions will hopefully attenuate the progressive rise in number of persons needing renal replacement therapy across our nation. References 1. Easterling RE. Racial factors in the incidence and causation of end stage renal disease. Trans Am Soc Artif Intern Organs 1977;23:28 –32. 2. Rostand SG, Kirk KA, Rutsky EA, et al. Racial differences in the incidence of treatment for end-stage renal disease. N Engl J Med 1982;306:1276 –9.
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3. President Clinton Announces New Racial and Ethnic Health Disparities Initiative. 1998. Available at: URL: http://raceandhealth.hhs.gov/sidebars/report.htm. 4. U.S. Renal Data System. USRDS 2001 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2001. Available at: URL: http://www. usrds.org/atlas.htm. 5. Jones CA, McQuillan GM, Kusek JW, et al. Serum creatinine levels in the US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 1998;32: 992–9. 6. Norris KC, Pan D, Owen WF. Risk factors for early renal disease in special populations [abstract]. Ethn Dis 2000;10: 310. 7. Agodoa LY, Appel L, Bakris GL, et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001;285:2719 –28. 8. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456 – 62. 9. Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996;334:939 – 45. 10. Monahan M, Tanji N, Klotman PE. HIV-associated nephropathy: An urban epidemic. Semin Nephrol 2001;21:393– 402. 11. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988 –1994. Diabetes Care 1998; 21:518 –24. 12. National Diabetes Fact Sheet: Incidence of diabetes. Available at: URL: http://www.cdc.gov/diabetes/pubs/facts98. htm#incidence. 13. Molyneaux LM, Constantino MI, McGill M, et al. Better glycaemic control and risk reduction of diabetic complications in Type 2 diabetes: comparison with the DCCT. Diabetes Res Clin Pract 1998;42:77– 83. 14. Anonymous. Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group. Kidney Int 1995;47: 1703–20. 15. Herman WH, Eastman RC. The effects of treatment on the direct costs of diabetes. Diabetes Care 1998;21(Suppl 3):C19 – 24. 16. Egger M, Davey Smith G, Stettler C, et al. Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis. Diabet Med 1997;14:919 –28. 17. Gautier JF, Beressi JP, Leblanc H, et al. Are the implications of the Diabetes Control and Complications Trial (DCCT) feasible in daily clinical practice? Diabetes Metab 1996;22:415–9. 18. Anonymous. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703–13. 19. Anonymous. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000;355:253–9.
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20. Jerums G, Allen TJ, Campbell DJ, et al. Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria. Am J Kidney Dis, 2001;37:890 –9. 21. Anonymous. Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data. Ann Intern Med 2001;134:370 –9. 22. Bakris GL, Copley JB, Vicknair N, et al. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int 1996;50: 1641–50. 23. Lievre M, Gueyffier F, Ekbom T, et al. Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis. The INDANA Steering Committee. Diabetes Care 2000;23(Suppl 2):B65–71. 24. Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis 2000;36:646 – 61. 25. Hennekens CH. Lessons from hypertension trials. Am J Med 1998;104(6A):50S–53S. 26. Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996;334: 13– 8. 27. Deubner DC, Tyroler HA, Cassel JC, et al. Attributable risk, population attributable risk and population attributable fraction of death associated with hypertension in a biracial population. Circulation 1975;52:901– 8. 28. Norris KC, Francis CK. Gender and ethnic differences and considerations in cardiovascular risk assessment and prevention in African-Americans. In: Wong N, Gardin JM, Black HR. Preventive Cardiology. New York: McGraw-Hill; 2000. p. 459 – 484. 29. Anonymous. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413– 46. 30. Klag MJ, Stamler J, Brancati FL, et al. End-stage renal disease in African-American and white men: 16-year MRFIT findings. JAMA 1997;277:1293– 8. 31. Coresh J, Wei GL, McQuillan G, et al. Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med 2001;161:1207–16. 32. Walker WG, Neaton JD, Cutler JA, et al. Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. JAMA 1992;268:3085–91. 33. Hebert LA, Kusek JW, Greene T, et al. Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group. Hypertension 1997;30:428 –35. 34. Rosansky SJ, Hoover DR, King L, et al. The association of blood pressure levels and change in renal function in hypertensive and nonhypertensive subjects. Arch Intern Med 1990; 150:2073– 6. 35. Rostand SG, Brown G, Kirk KA, et al. Renal insufficiency in treated essential hypertension. N Engl J Med 1989;320: 684 – 8. 36. McClellan W, Tuttle E, Issa A. Racial differences in the incidence of end-stage renal disease (ESRD) are not entirely explained by differences in the prevalence of hypertension. Am J Kidney Dis 1988;12:285–90.
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37. Pettinger WA, Lee HC, Reisch J, et al. Long-term improvement in renal function after short-term strict blood pressure control in hypertensive nephrosclerosis. Hypertension 1989;13:766 –72. 38. Toto R, Mitchell H, Smith RD, et al. Strict blood pressure control and progression of renal disease in hypertensive nephropathy. Kidney Int 1995;48:851–9. 39. Fernandes PF, Ellis PA, Roderick PJ, et al. Causes of End-Stage Renal Failure in Black Patients Starting Renal Replacement Therapy. Am J Kidney Dis 2000;36:301–9. 40. Perneger TV, Rossiter KA, Klag MJ, et al. Diagnosis of hypertensive end-stage renal disease: effect of patient’s race. Am J Epidemiol 1995;141:10 –5.
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41. Fogo A, Breyer JA, Smith MC, et al. Accuracy of the diagnosis of hypertensive nephrosclerosis in African-Americans: a report from the African-American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators. Kidney Int 1997;51:244 –52. 42. Klotman PE. HIV-associated nephropathy. Kidney Int 1999; 56:1161–76. 43. Winston JS, Burns GC, Klotman PE. The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy. Semin Nephrol 1998;18:373–7. 44. Freedman BI, Soucie MJ, Stone SM, et al. Familial clustering of end-stage renal disease in blacks with HIV-associated nephropathy. Am J Kidney Dis 1999;34:254 – 8.
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