| | Prevalence and Awareness of CKD Among African Americans: The Jackson Heart StudyReceived 10 April 2008; accepted 29 August 2008. BackgroundChronic kidney disease (CKD) leads to end-stage renal disease and is a growing epidemic throughout the world. In the United States, African Americans have an incidence of end-stage renal disease 4 times that of whites. Study DesignCross-sectional to examine the prevalence and awareness of CKD in African Americans. Setting & ParticipantsObservational cohort in the Jackson Heart Study (JHS). PredictorCKD was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2, the presence of albuminuria, or dialysis therapy. Outcomes & MeasurementsData from the JHS were analyzed. Medical history, including disease awareness and drug therapy, anthropometric measurements, and serum and urine samples, were obtained from JHS participants at the baseline visit. Associations between CKD prevalence and awareness and selected demographic, socioeconomic, health care access, and disease status parameters were assessed by using logistic regression models. ResultsThe prevalence of CKD in the JHS was 20%; CKD awareness was only 15.8%. Older participants had a greater prevalence, but also were more aware of CKD. Hypertension, diabetes, cardiovascular disease, hypercholesterolemia, hypertriglyceridemia, increasing age and waist circumference, and being single or less physically active were associated with CKD. Only advancing CKD stage was associated with awareness. LimitationsCross-sectional assessment, single urine measurement. ConclusionsThe JHS has a high prevalence and low awareness of CKD, especially in those with less severe disease status. This emphasizes the need for earlier diagnosis and increased education of health care providers and the general population. Recent studies show that the prevalence and incidence of end-stage renal disease (ESRD) and chronic kidney disease (CKD) have reached epidemic proportions in the United States and worldwide. An estimated 50 million people are affected, with approximately 1 million receiving renal replacement therapy.1, 2 In the most recent National Health and Nutrition Examination Survey (NHANES) report, Coresh et al3 calculated estimates of 8 million in the United States with stage 3 CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) and 12 million with microalbuminuria. Together, this places more than 6% of the US population at risk of the complications of ESRD. The prevalence of CKD in adults in NHANES was almost 17% in 1999 to 2004, which was 16% greater than during 1988 to 1994.4 The US Renal Data System 2006 Annual Data Report shows that a large proportion of the CKD population has the comorbid conditions of diabetes and hypertension.5 Although recent ESRD incident rates have leveled off at approximately 340 cases per million, the high rates of hypertension and diabetes in the younger employed population likely signify an upturn in the incident rate because 70% of all persons with ESRD have these diseases as their primary diagnosis.5 Older African Americans (age ≥ 60 years) in the United States have incident rates of ESRD of approximately 1,500 per million, more than 3 times their white counterparts; younger African Americans have similar increased incident rates.5 Because the personal, social, and economic costs of ESRD are high,6 there is a global challenge to prevent or slow the progression of CKD.7 The most serious consequences of untreated CKD include hypertension, cardiovascular disease (CVD), and ESRD, which leads to dialysis therapy and kidney transplantation, thus resulting in decreased quality of life, increased health care cost, and premature death.1, 6 There is evidence that these outcomes of CKD can be prevented or delayed with timely diagnosis and treatment.8, 9, 10, 11 Because of the increased risk of CKD progression to ESRD in the African American population, it was important to examine the prevalence of CKD, disease awareness, and degree of treatment in a large cohort, such as the Jackson Heart Study (JHS), versus such factors as diabetes, hypertension, obesity, level of physical activity, hypercholesterolemia, social status, income, and education. Methods  Study Design, Participants, and Measurements The JHS is a single-site longitudinal population-based study designed to prospectively explore the determinants (both individual and environmental) and genetic linkages that influence the development of CVD in African Americans. The sample consists of 5,302 women and men selected between 2000 and 2004 from a tricounty area of Mississippi: Hinds, Madison, and Rankin counties. The rationale for the study stems from the large disparity in cardiovascular mortality between Mississippi African Americans and Mississippi whites or African Americans from other parts of the United States.12, 13 Current findings have shown a high prevalence of hypertension (∼60%) and diabetes (∼20%),14 as well metabolic syndrome (∼40%).15 Overviews of the JHS,16 including sampling and recruitment,17 sociocultural,18 and laboratory methods,19 have been described previously. The baseline examination consisted of a home interview, self-administered questionnaires, and a clinic visit. Medications used in the prior 2 weeks were brought to the clinic and transcribed verbatim, with subsequent coding by a pharmacist using the Medispan dictionary with classification according to the Therapeutic Classification System. After an overnight fast, anthropometric and seated blood pressure measurements were obtained and venipuncture/urine collection was performed in accordance with the National Committee for Clinical Laboratory Standards published in 1999.20, 21, 22 Waist circumference (in centimeters) at the umbilicus, height (in centimeters), and weight (to 0.1 kg) were measured, and body mass index was computed by using these last 2 measurements (kilograms per square meter). Blood pressure was measured by trained technicians using a Hawksley random zero manometer and determined by using the arithmetic average of 2 readings obtained 1 minute apart after a 5-minute rest. Based on the physical activity questions, 4 index scores, Active Living, Work, Sport, and Home and Family Life, were obtained, with values for each ranging from 1 to 5 and summed to calculate the total physical activity score. All baseline participants were requested to contribute a 24-hour urine collection. Because some participants did not agree to the 24-hour urine collection, spot urine collections were later added to the protocol. Participants were provided with a sterile container and instructions for obtaining a clean-catch sample.21 Urine albumin and creatinine concentrations were obtained for each collection method. Urine albumin was measured using a human albumin kit (Dade Behring, Newark, DE) on a Dade Behring BN II nephelometer. Biochemical testing for serum and urine creatinine was performed at the University of Mississippi Medical Center Laboratory Reading Center by using a multipoint enzymatic spectrophotometric assay (Vitros CREA dry reaction slides on a Vitros 950 Ortho-Clinical Diagnostics analyzer, Raritan, NJ).19 Creatinine values were biochemically calibrated to the Cleveland Clinic–equivalent Minnesota Beckman CX3 assay (Beckman-Coulter Inc, Fullerton, CA) for analysis purposes. Variables CKD was defined as the presence of albuminuria, decreased eGFR less than 60 mL/min/1.73 m2, or dialysis therapy and classified into 5 stages according to the National Kidney Foundation (NKF) guidelines.23 The presence of albuminuria was determined by means of urine albumin-creatinine ratio based on spot or 24-hour urine values (albumin-creatinine ratio > 30 mg/g),24 and eGFR was calculated based on serum creatinine values using the isotope dilution mass spectrometry–traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation (GFR = 186.0 · [serum creatinine]−1.154 · age−0.203 · [0.742 if female] · [1.21 if African American]). CKD stages corresponded to ranges of GFR: stage 1, GFR of 90 mL/min/1.73 m2 or greater with the presence of albuminuria; stage 2, GFR of 60 to 89 mL/min/1.73 m2 with the presence of albuminuria; stage 3, GFR of 30 to 59 mL/min/1.73 m2; stage 4, GFR of 15 to 29 mL/min/1.73 m2; and stage 5, GFR less than 15 mL/min/1.73 m2. Participants for whom CKD status could not be determined based on available data, ie, if they had no serum creatinine or urinary protein values or only 1 normal value without the other measure, were excluded from the analyses. Although some studies define CKD based solely on eGFR,25 microalbuminuria has been clearly associated with progressive decrease in kidney function, particularly in individuals with diabetes.26 With the abundant evidence that early intervention (CKD stages 1 to 2) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) slows the progression of disease, a broader definition of CKD is warranted. Awareness of CKD was defined by a “yes” response to the question “Have you ever been told by a doctor or health care professional that you have kidney disease?” and/or self-report of being on dialysis therapy. Awareness of hypertension and diabetes was determined by a positive response to ever having been told of the diagnosis by a health care provider or a self-reported treatment for the condition. Because CKD was not included as a possible reason for taking medication on the questionnaire, any use of ACE inhibitors or ARBs was attributed to hypertension treatment, although they may have been dually used to slow or prevent CKD. Therefore, individuals with CKD receiving such medications were considered potentially treated for kidney disease in addition to treatment of hypertension; this likely overestimates the true number under treatment for CKD. Select sociodemographic factors, including age, sex, marital status, socioeconomic status (education, and family income level), health care access (insurance status and preventive health care), lifestyle behaviors (smoking and physical activity), CVD status, and CVD-related risk factors (waist circumference, presence of obesity, hypertension, diabetes, low high-density lipoprotein cholesterol level, hypercholesterolemia, or hypertriglyceridemia), were included to examine the relationship with CKD. CVD was defined as the presence of coronary heart disease (electrocardiogram-determined myocardial infarction or self-reported history of myocardial infarction or angioplasty) or cerebrovascular disease (self-reported history of stroke or carotid endarterectomy or angioplasty). Hypertension was defined as a measured blood pressure of 140/90 mm Hg or greater and/or use of antihypertensive medications. The presence of type 2 diabetes mellitus (diabetes) was determined as a measured fasting glucose level of 126 mg/dL or greater or use of antidiabetic agents. The presence of hypercholesterolemia was defined as an elevated fasting total cholesterol (≥200 mg/dL) or elevated low-density lipoprotein cholesterol (≥160 mg/dL) level and/or use of lipid-lowering medications. Hypertriglyceridemia was defined as elevated triglyceride levels (≥150 mg/dL) and/or treatment with fenofibrate or gemfibrozil, whereas sex-specific limits (<50 mg/dL for women and <40 mg/dL for men) were used to define low high-density lipoprotein cholesterol levels.15 Statistical Methods Participant characteristics were summarized descriptively (using mean ± SD for continuous variables and counts and percentages for categorical variables). Logistic regression models were used to identify baseline characteristics associated with CKD prevalence and awareness. First, the association between CKD prevalence and each socioeconomic, health care access, lifestyle, CVD, and CVD risk factor parameter described was tested by using logistic regression models controlling for age and sex. The association between CKD awareness and each listed parameter, as well as CKD stage, was tested by using logistic regression models controlling for age. Factors that were statistically significant (P < 0.05), as well as sex, then were included in the full model adjusting for potential confounders. Logistic regression analysis with backward stepwise elimination was performed to obtain the most parsimonious models. Odds ratios and 95% confidence intervals were estimated for each model. Only data from JHS participants meeting study inclusion criteria aged 35 to 84 years were used in regression analyses because participants outside that age range (n = 266) were included in the original sample only to maximize the size of the participating families in the family study component.27 Analyses were performed using SAS, version 9.1 (SAS Institute, Cary, NC). For comparison purposes, NHANES data released since 1999 were aggregated into a combined data set (1999 to 2004), and estimates were adjusted to the JHS sex-specific age, education, and income distribution (JHS-NHANES) using SUDAAN (RTI Int, Research Triangle Park, NC) to account for the complex sampling design. Results Descriptive Data After excluding participants with restricted consent (n = 23) or without sufficient serum (n = 56) or urine data (n = 1,792) to determine CKD status, 3,431 participants (2,154 women and 1,277 men) were used in these analyses. Of the included participants, 1,015 had 24-hour and 2,255 had spot urine collections; an additional 161 participants with missing urine data were classified as having CKD because of low eGFR or being on dialysis therapy. Table 1 lists baseline characteristics of the JHS by CKD status for the overall population and men and women. Participants with CKD reported lower income and lower level of education and had notably greater rates of CVD, diabetes, hypertension, hypercholesterolemia, and hypertriglyceridemia. They also tended to be older, more obese, and less physically active and less likely to be married or drink heavily, but were not different with respect to smoking than those without CKD. Nearly equal proportions of participants with and without CKD had insurance, but a smaller proportion of those without CKD used preventive care. Characteristics of included participants were similar to those of participants with eGFR alone (Table A1). | | |  | Characteristics | Overall | Men | Women | |
|---|
| No CKD (n = 2,746) | CKD (n = 685) | No CKD (n = 1,049) | CKD (n = 228) | No CKD (n = 1,697) | CKD (n = 457) | |
|---|
| Women (%) | 61.8 | 66.7 | | | | | | | Education ≥ high school (%) | 86.9 | 71.8 | 86.8 | 73.3 | 86.9 | 71.1 | | | Income ≥ $50,000 (%) | 39.6 | 22.9 | 53.1 | 29.6 | 31.1 | 19.5 | | | Marital status (% married) | 56.8 | 47.9 | 71.4 | 67.8 | 47.8 | 38.0 | | | Insured (%) | 87.0 | 88.2 | 86.8 | 87.6 | 87.1 | 88.5 | | | Preventive care (%) | 71.2 | 78.3 | 60.6 | 73.0 | 77.7 | 80.9 | | | Current smoker (%) | 11.6 | 11.6 | 15.0 | 15.6 | 9.5 | 9.6 | | | Heavy drinker (%) | 2.6 | 1.8 | 5.8 | 4.5 | 0.6 | 0.4 | | | Type 2 diabetes (%) | 12.9 | 39.7 | 9.4 | 44.7 | 15.1 | 37.2 | | | Hypercholesterolemia (%) | 57.0 | 87.5 | 54.2 | 86.2 | 58.7 | 88.1 | | | Low high-density lipoprotein cholesterol (%) | 38.1 | 42.3 | 33.8 | 37.6 | 40.8 | 44.5 | | | Hypertriglyceridemia (%) | 14.7 | 26.6 | 18.3 | 35.4 | 12.3 | 22.3 | | | Hypertension (%) | 30.2 | 47.1 | 30.9 | 44.4 | 29.8 | 48.3 | | | Cardiovascular disease (%) | 7.6 | 22.0 | 8.6 | 25.4 | 6.9 | 20.2 | | | Age (y) | 52.7 ± 12.6 | 61.1 ± 12.7 | 51.6 ± 12.7 | 60.3 ± 12.9 | 53.3 ± 12.5 | 61.5 ± 12.7 | | | Body mass index (kg/m2) | 31.4 ± 6.9 | 33.0 ± 7.6 | 29.5 ± 5.7 | 31.7 ± 7.4 | 32.5 ± 7.4 | 33.7 ± 7.7 | | | Waist (cm) | 99.4 ± 15.8 | 105.0 ± 16.7 | 100.1 ± 14.5 | 106.6 ± 16.4 | 98.9 ± 16.6 | 104.2 ± 16.8 | | | Physical activity score | 8.6 ± 2.5 | 7.2 ± 2.5 | 8.9 ± 2.5 | 7.2 ± 2.6 | 8.4 ± 2.5 | 7.1 ± 2.5 | | | Creatinine (mg/dL) | 1.0 ± 0.2 | 1.5 ± 1.3 | 1.1 ± 0.1 | 1.7 ± 1.4 | 0.9 ± 0.1 | 1.4 ± 1.3 | | | eGFR (mL/min/1.73 m2) | 89.6 ± 15.2 | 67.6 ± 27.2 | 90.5 ± 14.7 | 71.3 ± 27.2 | 89.1 ± 15.6 | 65.8 ± 27.0 | | | | |
Outcome Data Figure 1 shows prevalences of CKD for men and women in specific age groups. The overall prevalence of CKD was 20.0%. Figure 2 shows analogous data for albuminuria and low eGFR. The age group of 60 years and older had the greatest prevalence of albuminuria (∼19%) and low eGFR (∼11%). Table 2 lists CKD stages by eGFR for men and women and for different age groups. There were no large differences between men and women, but the 60-year-and-older age group was not only the largest group, but also had the greatest percentage with stages 3 (20%) and 4/5 (3%). For the overall study cohort, there were more individuals with stage 3 (9.6%) than any other stage. Main Results As listed in Table 2, Table 3, a very small percentage (15.8%) of those with CKD were aware of their disease, and there were no sex differences in awareness rates. Although awareness was reasonably high in those with stage 4/5 (65.9%), it was still lower than overall awareness of hypertension or diabetes. In those with mild to moderate CKD, awareness was minimal, with only 17.6% of those with stage 3 aware of their condition. Assuming that treatment with ACE inhibitors or ARBs equals implied therapy for CKD, just more than one-half (52%) were using antihypertensive medication recommended for CKD compared with treatment rates greater than 80% for hypertension (83.2%) and diabetes (85.4%). As noted in Methods, this assumption likely overestimates those treated for CKD. Table 4, Table 5 list results of logistic regression analyses of CKD prevalence and awareness, respectively. In sex- and age-adjusted analysis, the odds of CKD increased with hypertension, diabetes, CVD, hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol level, abdominal girth (waist circumference), and lower physical activity levels and decreased with higher levels of education and income, as well as being married and having insurance. Results from the fully adjusted and the most parsimonious models were consistent. The presence of hypertension, diabetes, CVD, hypertriglyceridemia, hypercholesterolemia, lower physical activity score, increasing waist girth, and age were independently associated with CKD. Only CKD severity was associated with awareness compared with those with stages 1/2. A subgroup analysis of participants with eGFR alone yielded essentially the same results with the exception of higher odds of CKD for women than men, as expected (Table A2). Discussion The findings of this cross-sectional cohort of African American adults enrolled in the JHS further confirm the increasing national epidemic of CKD, particularly in non-Hispanic African Americans, with prevalence estimates similar to the most current national estimates of 16.8% for the entire population reported by the Centers for Disease Control and Prevention from analyses of the 1999 to 2004 NHANES data.4 Older participants (≥60 years) in both the NHANES (39.4%) and JHS (31.7%) had a greater prevalence. The Centers for Disease Control and Prevention analyses showed that persons with albuminuria (albumin-creatinine ratio ≥ 17 mg/g for men and ≥ 25 mg/g for women; eGFR > 59 mL/min/1.73 m2) made-up 11.1% of the cohort, and those with eGFR less than 60 mL/min/1.73 m2 made-up 5.8%. Similar to those analyses, there was disparity in JHS participants with stages 1 and 2 CKD with proteinuria and relatively normal kidney function from those with CKD stage 3, which is often used as the definition of CKD. In the JHS, the more conservative NKF criteria were used to define albuminuria (albumin > 30 mg/d), whereas NHANES used the lower sex-specific cut-off values. A more recent analysis of the NHANES data (courtesy of the National Heart, Lung, and Blood Institute) adjusted to the JHS age and sex distribution with the same criteria as this study (Fig 3) showed an overall CKD prevalence of 22.2% in NHANES African Americans compared with 20% in the JHS. The cross-sectional nature of our data precludes any causal inferences, but it is interesting to note that this lower than national prevalence of CKD corresponds to a higher than national rate of blood pressure control in JHS participants with hypertension at baseline.14 Analyses of the data show that medical and socioeconomic factors are associated with CKD. As with other population studies,4, 28, 29 hypertension, diabetes, CVD, hypercholesterolemia, hypertriglyceridemia, abdominal obesity, and increasing age were strongly associated with CKD. As expected, the odds of having CKD progressively decreased with the increase in annual income, education level beyond primary school, and increasing activity score. A recent analysis of NHANES III also showed that African Americans had increased odds of albuminuria (odds ratios, 1.41 for nondiabetic individuals and 1.85 for those with diabetes) and low eGFR (odds ratios, 2.18 for nondiabetic individuals and 2.78 for those with diabetes) than whites after adjusting for baseline characteristics (such as age, sex, education, marital status, income, and blood pressure).24 These findings emphasize the importance of earlier diagnosis in this population. Although disease prevalence was high in the cohort, awareness of the disease was low, varying from approximately 13% in 21- to 39-year-olds to 17% in those 60 years and older. Older participants were not only more aware, but more likely to be treated for CKD (Table 3). For comparison, analogous data can be derived from the NKF Kidney Early Evaluation Program (KEEP), which consists of screenings of targeted populations with chronic diseases. In a report published in 2003,30 only 2.6% of 6,071 participants (43% of the cohort were African American) reported preexisting kidney disease, whereas 24.7% reported diabetes and 51.8% reported hypertension. Within this Kidney Early Evaluation Program cohort, 34% were in CKD stage 0 to 1; 50%, stage 2; and 16%, stages 3 to 5.30 New conditions identified through the screening were diabetes, 2%; hypertension, 35%; and kidney disease, 42% (eGFR < 60 mL/min/1.73 m2 or microalbuminuria). Eighty-six percent of these participants had health insurance coverage and had seen their physician within 1 year, which compares with the JHS insured percentages of 87% and 73% of the study cohort receiving preventive care in the past year. These data showed remarkably low rates of awareness in the JHS, which were similar for men and women and increased with age and stage of CKD. This was in sharp contrast to JHS participant awareness of other major conditions, such as diabetes, hypertension, and hypercholesterolemia, which ranged from 60% to 84%, exceeding that of CKD by 44% to 68%.14 Figure 3 shows CKD awareness in the JHS compared with age- and sex-adjusted data from NHANES (courtesy of the NHLBI) and showed low numbers in both studies. This lack of awareness highlights inadequate public awareness and health care provider education for patients with CKD. Worldwide, awareness of CKD likely is low. A recent study carried out in 6,001 participants in Taiwan31 showed awareness rates of 8% for CKD stage 3, 25% for stage 4, and 71% for stage 5. The prevalence of CKD stages 3 to 5 was 6.9% of the cohort, similar to the JHS. This directs attention to the international challenge of education of patients and health care providers concerning CKD. Based on the assumptions that treatment with an ACE inhibitor or ARB constituted a drug targeted to CKD, treatment of all age groups in the JHS was much better than awareness of the underlying disease. The assumption may not be true if studied carefully. Primary care physicians in Mississippi are just now receiving information for CKD stages (Daniel Bender, personal communication, Mississippi State Department of Health, April 5, 2008) and the need to carefully examine and treat “at-risk” patients. Therefore, treatment of patients with hypertension with ACE inhibitors or ARBs may be serendipitous. Despite this, the vast majority of the JHS cohort, who had insurance and at least a high school education, did not know they have CKD and were not being properly treated. This study is not without limitations. Data for this analysis were cross-sectional with a single urine collection. As in other epidemiological studies that used 2 parameters to define CKD, there could be slight bias toward prevalence because of incomplete laboratory studies. Use of eGFR by using the MDRD Study equation has come under criticism in recent years because the equation was developed for patients with kidney disease and not validated in a general population. Our definition of CKD depends on both albuminuria (with normal function) and eGFR and therefore may differ from earlier studies that used only low eGFR as the defining criteria. However, analyses of participants with GFR only (data shown in Appendix) showed results very similar to Table 4. Our measure of awareness differed from that used in NHANES in that it asked about “kidney disease,” rather than “weakened or failing kidneys.” Interviewers were carefully instructed to exclude answers that implied bladder infections and other urinary tract issues that would not indicate chronic problems of the kidney. Although the item was used previously in the ARIC (Atherosclerosis Risk in Communities) Study, there was no pretesting in persons with known CKD to determine how well it was understood or discriminated. Despite these limitations, the question provides an approximate assessment of this population and should be validated against other awareness questions to develop a standard item for use in epidemiological surveys of this type. Given the low overall response, errors likely would be in the direction of overestimating awareness. We were limited in our ability to fully examine several potential factors (smoking and alcohol) because of the small number of participants engaging in these behaviors. The strengths of the study are that it is the largest single-site study of African Americans, with extensive phenotypic data using actual pharmacist-coded medication information rather than self-reported medication use. Despite those limitations, it is clear that CKD is a looming national and international problem on par with diabetes, with consequences as severe and costly. It is imperative that new approaches be implemented to increase awareness, diagnosis, and treatment for both the health care provider and the patient. African Americans are known to have an ESRD rate 4 times that of whites.32 The high prevalence of CKD in the JHS further emphasizes the nature of the CKD threat to African Americans and the need for sustained, integrated, population-based programs to prevent, delay the progression of, and treat CKD. We are on the cusp of a large national public health campaign to provide education to the general public and primary care providers. Our data strongly support the necessity of this kind of national effort coupled with localized efforts to enhance screening and awareness in high-risk populations. 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32. 32Collins AJ. 2006 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Am J Kidney Dis. 2007;49(suppl 1):S100–S104. 1 Department of Medicine, University of Mississippi Medical Center, Jackson, MS 2 School of Nursing, University of Mississippi Medical Center, Jackson, MS 3 Jackson Heart Study, Jackson State University, Jackson, MS 4 National Heart, Lung, and Blood Institute, Bethesda, MD 5 University of South Alabama, Mobile, AL  Address correspondence to Michael F. Flessner, MD, PhD, John Bower Professor and Chair, Division of Nephrology, School of Medicine, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505
PII: S0272-6386(08)01575-8 doi:10.1053/j.ajkd.2008.08.035 © 2009 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved. | |
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