| | Kidney Function and Cognitive Impairment in US Adults: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) StudyReceived 8 August 2007; accepted 12 May 2008. published online 01 July 2008.
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The Cognition–Kidney Disease Connection: Lessons From Population-Based Studies in the United States
Daniel E. Weiner
American Journal of Kidney Diseases
August 2008 (Vol. 52, Issue 2, Pages 201-204)
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BackgroundThe association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity. Study DesignCross-sectional. Setting & Participants23,405 participants (mean age, 64.9 ± 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a study of stroke risk factors in a large national sample. PredictorEstimated glomerular filtration rate (eGFR). OutcomeCognitive impairment. MeasurementsChronic kidney disease (CKD) was defined as eGFR less than 60 mL/min/1.73 m2. Kidney function was analyzed in 10-mL/min/1.73 m2 increments in those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the 6-Item Screener, and participants with a score of 4 or less were considered to have cognitive impairment. ResultsCKD was associated with an increased prevalence of cognitive impairment independent of confounding factors (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.43). In patients with CKD, each 10-mL/min/1.73 m2 decrease in eGFR less than 60 mL/min/1.73 m2 was associated with an 11% increased prevalence of impairment (odds ratio, 1.11; 95% confidence interval, 1.04 to 1.19). Exploratory analyses showed a nonlinear association between eGFR and prevalence of cognitive impairment, with a significant increased prevalence of impairment in those with eGFR less than 50 and 100 mL/min/1.73 m2 or greater. LimitationsLongitudinal measures of cognitive function were not available. ConclusionsIn US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore, screening for impairment should be considered in all adults with CKD. Chronic kidney disease (CKD) and dementia are common conditions in the elderly that have growing public health significance as the US population ages. Persons with CKD have an increased risk of stroke and a high burden of cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia, which, in turn, are linked to cognitive impairment.1, 2, 3 Studies of selected populations suggested that CKD is an independent risk factor for cognitive impairment and dementia4, 5, 6; however, these studies were largely restricted to elderly cohorts with limited representation of African Americans, had small numbers of participants with advanced CKD, and used serum creatinine level alone as a proxy for glomerular filtration rate (GFR). Conversely, most large epidemiological studies of cardiovascular risk factors and cognitive impairment did not include kidney function as a covariate.1, 2, 3 The goals of this study are to assess the association between kidney function and cognitive impairment in a population-based cohort across a wide spectrum of kidney disease severity and determine whether the associations are independent of traditional cardiovascular risk factors. Methods  Study Design The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study is a nationally representative sample of adults aged 45 years and older in the US population. Recruitment of the REGARDS cohort has been described previously.7 Briefly, participants were identified from commercially available lists of residents and recruited through an initial mailing followed by telephone contact. The cooperation rate in REGARDS was 64.6%, and the participation rate was 44.7%. Both are similar to rates in other cohort studies.8, 9 The sample is designed so that approximately one-half the participants will be African American and one-half will be white, and one-half will be men and one-half will be women. Individuals living in the stroke belt were oversampled. Recruitment began in January 2003; on completion of recruitment, the REGARDS cohort will consist of a sample of 30,000 participants with follow-up extending for up to 4 years.7 Data Data used in these analyses were obtained from 2 sources: a telephone interview and a subsequent in-home examination conducted by a nurse or other health professional. During the telephone interview, demographic characteristics, self-report of health conditions, and use of antihypertensive or diabetes medications were obtained. During the subsequent in-home examination, anthropometric measurements and an electrocardiogram were obtained. Blood pressure was measured twice with the participant seated, and the average of measurements was used. Blood was drawn in the fasting state, with samples shipped to a central laboratory for determination of serum markers, including creatinine, total and high-density lipoprotein cholesterol, and glucose. Cardiovascular Risk Factors For these analyses, we included cardiovascular and stroke risk factors previously identified to be associated with CKD, cognitive impairment, or both. Hypertension was defined as systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or self-reported current treatment for hypertension. Diabetes was defined as fasting glucose level of 126 mg/dL or greater (glucose in mg/dL may be converted to mmol/L by multiplying by 0.05551), nonfasting glucose level of 200 mg/dL or greater, or self-reported current treatment for diabetes. Increased cholesterol was defined as a total cholesterol level of 240 mg/dL or greater (cholesterol in mg/dL may be converted to mmol/L by multiplying by 0.02586) or self-reported current treatment for increased cholesterol level. Obesity was defined as a body mass index of 30 kg/m2 or greater. Tobacco use was categorized as current or past use versus never use. Left ventricular hypertrophy and atrial fibrillation were ascertained by means of electrocardiogram. Prevalent cerebrovascular disease was defined as self-report of a diagnosed stroke or transient ischemic attack. Prevalent coronary heart disease was defined as electrocardiographic evidence or self-report of myocardial infarction, coronary artery bypass surgery, coronary angioplasty, or coronary stent placement. Education level was classified as less than high school education, high school education, or some post–high school education, and geographic region was categorized as stroke belt or buckle versus other regions, as previously described.7 Kidney Function In 2007, after completion of REGARDS recruitment, the REGARDS laboratory at the University of Vermont changed creatinine reagents to a method traceable to creatinine determined by means of isotope dilution mass spectrometry (IDMS). Fifty samples were run in duplicate comparing the original method with the IDMS-traceable method, yielding the following calibration equation: IDMS-traceable creatinine = −0.06 + 0.953 * creatinine. In addition, the Vermont calibration was confirmed with 200 serum samples sent to the Cleveland Clinic, resulting in the following calibration equation: calibrated creatinine = −0.06 + 0.98 * REGARDS creatinine. Because these 2 equations were nearly identical, the Vermont equation was used to convert the original REGARDS creatinine values to standardized IDMS-traceable values for estimation of GFR (eGFR) using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation10: This approach was used to obtain eGFR values for the present report and will be used in future publications concerning the REGARDS cohort. Cognitive Function Starting on January 1, 2004, a 6- item cognitive screening examination was incorporated into the REGARDS baseline telephone interview and administered to all participants enrolled on or after that date. Designed for either in-person or telephone administration, the 6-Item Screener is a test of global cognitive function that includes recall and temporal orientation items derived from the widely used Mini-Mental State Examination (Appendix A).11, 12 Scores range from 0 to 6, and a score of 4 or less has been shown to have sensitivity of 74.2% to 84.0% and specificity of 80.2% to 85.3% in community and clinical samples for a diagnosis of cognitive impairment.11 Statistical Analysis We used standard descriptive statistics to assess baseline characteristics and test differences in characteristics between participants with and without CKD and with and without cognitive impairment. We used multivariable logistic regression models to determine the association (expressed as odds ratio [OR] and 95% confidence interval [CI]) between kidney function and cognitive impairment. We first modeled kidney function in 2 ways: as the binary variable CKD (defined by National Kidney Foundation guidelines13 as GFR of 60 mL/min/1.73 m2 [GFR in mL/min/1.73 m2 may be converted to mL/s/1.73 m2 by multiplying by 0.01667]) and as an ordinal term for eGFR in 10-mL/min/1.73 m2 intervals (using those with eGFR ≥ 60 mL/min/1.73 m2 as the reference category). Models were adjusted for demographic characteristics (age, sex, race, education, and region), prevalent cardiovascular disease (stroke/transient ischemic attack and coronary heart disease), and individual cardiovascular risk factors. We included interaction terms for kidney function with race, age, and cardiovascular risk factors to determine whether effect modification was present. To confirm results, we performed several sensitivity analyses. First, we adjusted for depressive symptoms (assessed by using the Center for Epidemiological Studies-Depression 4-item scale14) in addition to cardiovascular risk factors. Second, we performed the analysis using multiple imputation techniques for missing data. In exploratory analyses, we then evaluated these associations across a wide range of eGFR values to determine the association between kidney function and cognitive impairment in those typically classified as having normal kidney function. For these models, we incorporated linear and quadratic terms for GFR, or eGFR strata ranging from 10 to 19 mL/min/1.73 m2 to 100 mL/min/1.73 m2 or greater. P less than 0.05 is considered statistically significant. Results A total of 24,512 participants were recruited into the cohort between January 1, 2004, and November 1, 2007. Of these participants, 23,499 had a nonmissing serum creatinine measurement, and 23,469 of these participants underwent cognitive function testing (Fig 1). We excluded 64 individuals with eGFR less than 10 mL/min/1.73 m2, leaving 23,405 participants in the analytic cohort. Participants included in our analyses had a mean age of 64.9 ± 9.6 (SD) years, 41.0% were African American, and 40.5% were men (Table 1). CKD was present in 11.0% (n = 2,586) of the sample (Fig 2A). Compared with participants without CKD, participants with CKD were older and more likely to be women and white. Participants with CKD had a greater prevalence of stroke/transient ischemic attack, coronary heart disease, diabetes, hypertension, obesity, left ventricular hypertrophy, and atrial fibrillation and a lower prevalence of increased cholesterol levels. Approximately 8% of the sample (n = 1,830) had a score of 4 or less on the 6-Item Screener, indicative of impaired cognitive function (Fig 2B). | | |  | | All Participants (N = 23,405) | CKD (GFR < 60 mL/min/1.73 m2) (N = 2,586) | No CKD (GFR ≥ 60 mL/min/1.73 m2) (N = 20,819) | P | |
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| Demographics | | | | | | |  Age (y) | 64.9±9.6 | 71.1±9.3 | 64.1±9.4 | <0.001 | | | Men | 9,469(40.5) | 991(38.3) | 8,478(40.7) | 0.02 | | | African American | 9,588(41.0) | 986(38.1) | 8,602(41.3) | 0.002 | | | Region | | | | 0.008 | | | Stroke belt | 8,218(35.1) | 841(32.5) | 7,377(35.5) | | | | Stroke buckle | 5,045(21.6) | 600(23.2) | 4,445(21.4) | | | | Other region | 10,127(43.3) | 1,143(44.2) | 8,984(43.2) | | | | Education | | | | <0.001 | | | <High school | 2,736(11.7) | 427(16.5) | 2,309(11.1) | | | | High school | 6,106(26.1) | 712(27.6) | 5,394(25.9) | | | | Post–high school/professional | 14,543(62.1) | 1,445(55.9) | 7,320(63.0) | | | | Comorbidity | | | | | | | Prior stroke or TIA | 2,197(9.5) | 475(18.6) | 1,722(8.3) | <0.001 | | | Coronary heart disease | 3,049(13.0) | 645(24.9) | 2,404(11.6) | <0.001 | | | Diabetes | 4,780(20.5) | 851(33.0) | 3,929(19.0) | <0.001 | | | Hypertension | 13,407(57.6) | 2,051(79.7) | 11,356(54.8) | <0.001 | | | Increased cholesterol | 12,725(54.9) | 1,156(45.1) | 11,569(56.1) | <0.001 | | | Tobacco use(ever v never) | 12,419(53.3) | 1,342(52.0) | 11,077(53.4) | 0.2 | | | Obese | 8,978(38.6) | 1,065(41.7) | 7,913(38.3) | <0.001 | | | Left ventricular hypertrophy | 1,459(6.3) | 219(8.7) | 1,240(6.1) | <0.001 | | | Atrial fibrillation | 2,020(8.8) | 354(14.1) | 1,666(8.2) | <0.001 | | | Serum creatinine(mg/dL) | 1.00±0.3 | 1.6±0.6 | 0.9±0.2 | <0.001 | | | Estimated GFR (mL/min/1.73 m2) | 85.9±23.7 | 47.7±10.4 | 90.7±20.3 | <0.001 | | | | |
In unadjusted analyses, CKD, as well as several other cardiovascular risk factors, was associated with a significant increased prevalence of cognitive impairment (Table 2). The association remained significant after additional adjustment for demographic characteristics, prevalent cardiovascular disease, and cardiovascular risk factors (OR, 1.23; 95% CI, 1.06 to 1.43). When eGFR was modeled as an ordinal variable in patients with CKD, each 10-mL/min/1.73 m2 decrease in GFR less than 60 mL/min/1.73 m2 was associated with an 11% increased prevalence of impairment (OR, 1.11; 95% CI, 1.04 to 1.19) after accounting for confounding factors (Table 3). | | | | Cardiovascular Risk Factor | Cognitive Impairment (N = 1,830) | No Cognitive Impairment (N = 21,566) | P | |
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| Age (y) | | | <0.001 | | | 45-55 (%) | 8.0 | 15.9 | | | | 56-65 (%) | 26.2 | 37.8 | | | | 66-75 (%) | 35.2 | 31.0 | | | | 76-85 (%) | 25.2 | 13.7 | | | | >85(%) | 5.4 | 1.6 | | | | Men (%) | 46.7 | 39.9 | <0.001 | | | Education | | | <0.001 | | | <High school (%) | 25.1 | 10.6 | | | | High school (%) | 30.5 | 25.7 | | | | Post–high school/professional (%) | 44.4 | 63.7 | | | | CKD (%) | 17.3 | 10.5 | <0.001 | | | Prior stroke or TIA (%) | 15.7 | 8.9 | <0.001 | | | Coronary heart disease (%) | 18.4 | 12.6 | <0.001 | | | Diabetes (%) | 28.0 | 19.9 | <0.001 | | | Hypertension (%) | 66.1 | 56.9 | <0.001 | | | Increased cholesterol (%) | 55.7 | 54.8 | 0.5 | | | Tobacco use (ever v never) (%) | 54.7 | 53.1 | 0.2 | | | Obese (%) | 37.4 | 38.8 | 0.2 | | | Left ventricular hypertrophy (%) | 11.3 | 5.9 | <0.001 | | | Atrial fibrillation (%) | 9.8 | 8.8 | 0.1 | | | | |
| | | | Kidney Function | Adjusted Odds Ratio (95% confidence interval)⁎ | |
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| CKD v no CKD | 1.23(1.06-1.43) | | | Per 10-mL/min/1.73 m2 decrease in GFR (reference: GFR ≥ 60 mL/min/1.73 m2) | 1.11(1.04-1.19) | | | | |
| ⁎ Model adjusted for age, sex, race, education, region, prevalent stroke/transient ischemic attack, coronary heart disease, diabetes, hypertension, increased cholesterol level, smoking, obesity, left ventricular hypertrophy, and atrial fibrillation. |
The association between kidney function and cognitive impairment did not vary by age, race, or cardiovascular risk factors such as diabetes or prior stroke (all P for interaction terms were not significant). For example, in participants younger than the median age of 65 years, there was an 11% increased risk of impairment for each 10-mL/min/1.73 m2 decrease in eGFR less than 60 mL/min/1.73 m2 (OR, 1.11; 95% CI, 0.97 to 1.26). In participants 65 years and older, there was a 17% increased risk of impairment for each 10-mL/min/1.73 m2 decrease in eGFR less than 60 mL/min/1.73 m2 (OR, 1.17; 95% CI, 1.09 to 1.23). To confirm the primary findings, we performed several additional analyses. When we adjusted for depressive symptoms in addition to cardiovascular risk factors, the association between low GFR and cognitive impairment remained robust (OR, 1.11; 95% CI, 1.04 to 1.19). We also performed the analyses using multiple imputations for missing data. The results were materially unchanged. We then evaluated the prevalence of cognitive impairment across a wide range of eGFRs, rather than focusing on those with CKD. There was a nonlinear or U-shaped association between eGFR and cognitive impairment, with an inflection point around 70 mL/min/1.73 m2 (Fig 3). After multivariable adjustment, there were significant associations between eGFR strata less than 50 mL/min/1.73 m2 and cognitive impairment, as well as a trend toward a modest increase in impairment in those with eGFR of 50 to 70 mL/min/1.73 m2. The relationship seemed to differ from that of eGFR with cerebrovascular disease, where prevalence increased below an eGFR threshold of 70 mL/min/1.73 m2. Conversely, although the inflection point appeared to be similar, there was also a significant increased prevalence of cognitive impairment in those with eGFR of 100 mL/min/1.73 m2 or greater (Table 4) that persisted after multivariable adjustment (P for GFR quadratic term <0.001). Inclusion of linear and quadratic terms for body mass index, rather than the binary variable obesity, did not alter these associations. | | | | GFR (mL/min/1.73 m2) | Unadjusted | Demographics Adjusted⁎ | Multivariable Adjusted† | |
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| ≥100 | 1.26(1.08-1.47) | 1.20(1.02-1.41) | 1.18(1.01-1.39) | | | 90-99 | 1.26(1.05-1.51) | 1.13(0.94-1.36) | 1.13(0.94-1.36) | | | 80-89 | 1.00(referent) | 1.00(referent) | 1.00(referent) | | | 70-79 | 1.04(0.87-1.24) | 1.05(0.88-1.25) | 1.04(0.87-1.24) | | | 60-69 | 1.37(1.14-1.64) | 1.16(0.96-1.40) | 1.14(0.94-1.37) | | | 50-59 | 1.69(1.36-2.10) | 1.27(1.01-1.59) | 1.22(0.97-1.53) | | | 40-49 | 2.26(1.75-2.91) | 1.51(1.16-1.97) | 1.44(1.10-1.89) | | | 30-39 | 2.34(1.65-3.32) | 1.51(1.05-2.18) | 1.44(1.00-2.08) | | | 20-29 | 2.99(1.82-4.90) | 1.80(1.08-3.02) | 1.61(0.95-2.71) | | | 10-19 | 3.51(1.75-7.06) | 2.16(1.06-4.44) | 1.86(0.90-3.82) | | | | |
| ⁎ Model adjusted for age, sex, race, education, and region. †Model adjusted for age, sex, race, education, region, prevalent stroke/transient ischemic attack, coronary heart disease, diabetes, hypertension, increased cholesterol level, smoking, obesity, left ventricular hypertrophy, and atrial fibrillation. |
Discussion In a large national sample of African American and white adults, individuals with lower levels of kidney function were more likely to have cognitive impairment compared with individuals with normal kidney function, independent of prevalent cardiovascular disease and cardiovascular risk factors. These results suggest that CKD, in addition to other modifiable cardiovascular risk factors, may be an important marker of cognitive impairment in US adults. These results confirm and extend previous studies of elderly populations that had limited representation of African Americans and individuals with advanced CKD. In the Health, Aging, and Body Composition Study, we found that elderly individuals with CKD, defined similarly to the present study, had a 1.3- to 2.4-fold greater risk of cognitive decline during 4 years of follow-up, even after accounting for a number of confounding factors.4 In a cross-sectional study of menopausal women participating in the Heart Estrogen/progestin Replacement Study, lower eGFR was associated with poorer performance on tests of global cognition, executive function, language, and memory.5 When Heart Estrogen/progestin Replacement Study participants were stratified by eGFR, only women with eGFR less than 30 mL/min/1.73 m2 had a significantly increased prevalence of impairment. In the Cardiovascular Health Study, Seliger et al6 found an association between serum creatinine concentration and risk of incident dementia during a median 6 years of follow-up that was dependent on self-reported health status. In older individuals with good or excellent health, increased serum creatinine concentration was associated with a 62% increased risk of dementia; however, there was no association between kidney function and incident dementia in the subgroup of individuals with poor or fair self-reported health. Recently, Hailpern et al15 reported that moderate CKD, defined as eGFR of 30 to 59 mL/min/1.73 m2, was associated with poorer concentration and attention in 20- to 59-year-old National Health and Nutrition Examination Survey (NHANES) participants. Compared with these previous studies, the large sample size of REGARDS allowed us to examine the association between GFR and cognitive impairment across a wider spectrum of kidney function. Our results confirm that CKD is associated with an increased prevalence of cognitive impairment and suggest that impairment may occur earlier in the course of kidney disease than previously recognized. We found a significant increase in prevalence of impairment for those with eGFR less than 50 mL/min/1.73 m2 and a trend toward an increased prevalence of impairment in those typically classified as having normal or near-normal kidney function (eGFR, 50 to 70 mL/min/1.73 m2) relative to participants with eGFR of 80 to 89 mL/min/1.73 m2. This finding should be interpreted with caution because these were exploratory analyses and the MDRD Study equation is known to be less accurate in this range.16 If confirmed in future studies, this would suggest that even small reductions in kidney function are associated with clinically significant consequences for cognitive functioning. We also noted a significant nonlinear association between eGFR and the prevalence of cognitive impairment. Whether this observation reflects misclassification caused by confounding from malnutrition or other factors is unclear. Nevertheless, it is worth noting because studies that do not account for this nonlinear association may underestimate the true association between CKD and cognitive impairment. Future studies using cystatin C, a novel marker of kidney function currently being assayed in REGARDS,17 may clarify the association between kidney function and cognitive function in those with normal eGFR. Individuals with CKD are frequently prescribed cumbersome medical regimens, and they must understand and weigh complex medical choices, including the decision to undergo kidney transplantation, the decision to initiate dialysis therapy, and the choice of dialysis modality. In addition to other factors, the high prevalence of cognitive impairment in persons with CKD may explain why practice guidelines for blood pressure management, preemptive vascular access placement, and other clinical targets remain difficult to achieve. Although screening for cognitive impairment generally is not a routine part of CKD care, accurate identification and treatment of persons with cognitive impairment may facilitate improved adherence with dietary and pharmacological therapies and aid in dialysis and long-term care planning. The causes of cognitive impairment in persons with CKD cannot be determined from the present study, although these results suggest that traditional cardiovascular and stroke risk factors do not fully account for the association between reduced kidney function and cognitive impairment. In addition to traditional risk factors, CKD also is associated with a number of novel cardiovascular risk factors, including inflammation, oxidative stress, anemia, vascular calcification, and hyperhomocysteinemia, that may have an important role in the development and progression of cognitive impairment.18, 19, 20 REGARDS participants were selected by using population-based sampling strategies; therefore, results of this study should be broadly generalizable to the US adult population. Nevertheless, several limitations should be noted. These analyses were cross-sectional; therefore, whether CKD is a marker for other factors that lead to cognitive impairment or a true causal risk factor cannot be concluded. Ongoing longitudinal studies of patients with CKD and cognitive function in REGARDS and other cohorts will provide additional support for the hypothesis that CKD independently contributes to cognitive impairment. The 6-Item Screener is a relatively insensitive measure of cognitive function and does not test different domains of cognitive function. The finding of such a strong association using a relatively insensitive measure of cognitive function only emphasizes the true strength of the association. The use of more sensitive measures of cognitive function and, in particular, measures of executive function associated with vascular causes of cognitive impairment may have strengthened the associations reported here. Such measures were recently added to REGARDS follow-up assessments and will be available for future studies. Finally, although we adjusted for a large number of cardiovascular risk factors and for the presence of cardiovascular disease, residual confounding may still exist because of unmeasured comorbidity or misclassification. In African American and white US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment independent of traditional cardiovascular risk factors. The prevalence of impairment appears to increase early in the course of kidney disease; thus, screening for impairment should be considered in all adults with CKD. Given the high prevalence of CKD in US adults and the adverse consequences of cognitive impairment, future clinical trials to improve cognitive function should consider targeting this high-risk population. Acknowledgements The authors acknowledge the participating investigators and institutions: University of Alabama at Birmingham, Birmingham, AL (Study PI, Data Coordinating Center, Survey Research Unit): George Howard, Leslie McClure, Virginia Howard, Libby Wagner, Virginia Wadley, Rodney Go; University of Vermont (Central Laboratory): Mary Cushman; Wake Forest University (ECG Reading Center): Ron Prineas; Alabama Neurological Institute (Stroke Validation Center, Medical Monitoring): Camilo Gomez, David Rhodes, Susanna Bowling; University of Arkansas for Medical Sciences (Survey Research): LeaVonne Pulley; Examination Management Services Inc (In-Home Visits): Andra Graham; National Institute of Neurological Disorders and Stroke, National Institutes of Health (funding agency): Claudia Moy. Support: Dr Kurella Tamura is supported by a research grant from the Amgen Nephrology Institute Junior Faculty Research Support Program. This research project is supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services. The Renal REGARDS study is supported by an unrestricted educational grant from Amgen Corp (B. Newsome, Principal Investigator). Financial Disclosure: None. Appendix A. 
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1 Department of Medicine, University of California San Francisco, San Francisco, CA 2 Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 3 Birmingham/Atlanta VA Geriatric, Research, Education and Clinical Center, Birmingham, AL 4 Department of Neurology, University of California, San Francisco, CA 5 Department of Psychiatry, University of California, San Francisco, CA 6 Department of Epidemiology and Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 7 Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 8 Emory University School of Medicine, Renal Division, Atlanta, GA.  Address correspondence to Manjula Kurella Tamura, MD, MPH, Ste 430 Laurel Heights, University of California, San Francisco, CA.
PII: S0272-6386(08)00877-9 doi:10.1053/j.ajkd.2008.05.004 © 2008 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved. | |
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