Racial Differences in Determinants of Live Donor Kidney Transplantation in the United States

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1 American Journal of Transplantation 2013; 13: Wiley Periodicals Inc. C Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons doi: /ajt Racial Differences in Determinants of Live Donor Kidney Transplantation in the United States T. S. Purnell 1,2, *, P. Xu 3, N. Leca 4 and Y. N. Hall 3 1 Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 2 Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD 3 Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington 4 Kidney Pancreas Transplant Section, Division of Nephrology, University of Washington, Seattle, WA *Corresponding author: Tanjala S. Purnell, tpurnel1@jhmi.edu Few studies have compared determinants of live donor kidney transplantation (LDKT) across all major US racial-ethnic groups. We compared determinants of racial-ethnic differences in LDKT among patients who initiated treatment for end-stage kidney disease during We performed proportional hazards and bootstrap analyses to estimate differences in LDKT attributable to sociodemographic and clinical factors. Mean LDKT rates were lowest among blacks (1.19 per 100 person-years [95% CI: ]), American Indians/Alaska Natives-AI/ANs (1.40 [ ]) and Pacific Islanders (1.10 [ ]), intermediate among Hispanics (2.53 [ ]) and Asians (3.89 [ ]), and highest among whites (6.46 [ ]). Compared with whites, the largest proportion of the disparity among blacks (20%) and AI/ANs (29%) was attributed to measures of predialysis care, while the largest proportion among Hispanics (14%) was attributed to health insurance coverage. Contextual poverty accounted for 16%, 4%, 18%, and 6% of the disparity among blacks, Hispanics, AI/ANs and Pacific Islanders but none of the disparity among Asians. In the United States, significant disparities in rates of LDKT persist, but determinants of these disparities vary by race-ethnicity. Efforts to expand preeskd insurance coverage, to improve access to high-quality predialysis care and to overcome socioeconomic barriers are important targets for addressing disparities in LDKT. Key words: Disparities, end-stage kidney disease, ethnicity, live donor kidney transplantation, race Abbreviations: AI/AN, American Indian/Alaska Native; CKD, chronic kidney disease; ESA, erythropoieisstimulating agent; ESKD, end-stage kidney disease; LDKT, live donor kidney transplantation; OPO, Organ Procurement Organization; UNOS, United Network for Organ Sharing; US, United States; USRDS, United States Renal Data System Received 11 September 2012, revised 08 March 2013 and accepted 15 March 2013 Introduction Despite the success of live donor kidney transplantation (LDKT) as an optimal treatment for patients with end-stage kidney disease (ESKD) (1,2), significant racial-ethnic disparities in attainment of LDKT persist (3 5). In the United States, racial-ethnic minorities experience disproportionately high rates of ESKD; yet for over two decades, minority patients have been consistently less likely than their white counterparts to undergo LDKT (3 6). Determinants of disparities in LDKT appear to operate on multiple levels and may include racial-ethnic differences in individual- and area-level factors such as differences in socioeconomic status, chronic disease burden, healthcare access, and in attitudes and knowledge regarding LDKT (7 14). As evidenced by geographic differences in transplant rates, population factors such as the disproportionately high burden of clinical comorbidities within minority communities and disparities in area resource allocation (i.e. contextual poverty) may also contribute to these differences (15 19). To date, prior studies have not quantified the extent to which these individual and area-level factors might contribute to disparities in LDKT across all major US racial-ethnic groups. Furthermore, the extent to which these measures might differentially impact LDKT access for specific racial-ethnic groups in the United States is also poorly understood. To address these issues, we examined data on a nationally inclusive population of adults who initiated treatment for ESKD during in order to better understand the relative contributions of individual- and arealevel determinants of LDKT across major racial-ethnic groups in the United States. We hypothesized that LDKT rates would be lower among racial-ethnic minorities compared with whites but that determinants of delays in LDKT would vary according to race-ethnicity. 1557

2 Purnell et al. Methods Data sources We obtained individual patient-level data from the US Renal Data System (USRDS) registry (3) and the United Network for Organ Sharing (UNOS) Kidney Transplant file, and area-level socioeconomic data from the 2000 US Census at the level of the five-digit zip code tabulation area. Patient-level covariates We extracted patient-level covariates that might confound or potentially mediate the association of race-ethnicity and time to transplantation based on prior studies (6 24). Sociodemographic covariates included age, sex and health insurance coverage (Medicare, Medicaid, employer group insurance, other insurance or no insurance). We examined the following comorbid conditions from the 2005 Medical Evidence form: cardiovascular disease, chronic lung disease, diabetes, poor functional status (requiring assistance with daily activities, inability to ambulate or transfer or institutionalized at an assisted living or nursing home facility), and active drug, alcohol or tobacco use at the time of initiating treatment for ESKD. We further identified patients who received nephrology care, who had moderate to severe anemia (hemoglobin <10 g/dl), who had hypoalbuminemia (serum albumin concentration <3.5 g/dl) and who were prescribed an erythropoiesisstimulating agent prior to ESKD because prior studies have reported racialethnic differences in these process measures and because these measures are associated with time to transplantation (14). We divided patients into World Health Organization-designated categories of body mass (Quetelet s) index (25). Finally, because regional competing rates of deceased donor kidney transplantation might influence a subject s decision to pursue LDKT, we assigned each patient to the Organ Procurement Organization (OPO) region in which she or he resided at ESKD onset (26). Study sample We identified all persons aged years who initiated treatment for ESKD in the United States between June 30, 2005 and September 23, 2008 (N ¼ ). We selected the initial time period in order to leverage data on predialysis care measures from the Centers for Medicare and Medicaid Services (CMS) 2005 Medical Evidence Form (Form-2728-U3) (3). To reduce the potential for race-ethnicity misclassification bias, we excluded 691 (0.3%) subjects who did not have a race or ethnicity assignment in the USRDS Patients file or Medical Evidence file, or for whom race was reported differently in these two files. Because kidney transplantation is rarely performed in subjects with known malignancies, we excluded subjects who were identified as having cancer at the time of ESKD. To further limit our study population to those individuals who might be medically eligible for LDKT, we restricted the cohort to patients aged who receive the vast majority of LDKT (92% of LDKT have been performed in patients younger than 65) (26). Finally, because area-based proxies of socioeconomic status were important covariates of interest, we further excluded 42 subjects who did not have a residential zip code. The analytic sample consisted of the remaining subjects. Outcome variables The primary outcome was time from ESKD onset to receipt of a first LDKT. For all analyses, we censored patients at the time of death (N ¼ ), deceased-donor kidney transplantation (N ¼ 8 214) or the end of the study observation period on September 30, Patients who underwent preemptive LDKT (N ¼ 4 157) were assigned a survival time of 1 day. Primary explanatory variable The primary explanatory variable for all analyses was patient race-ethnicity based on information collected at the time of ESKD onset. We defined raceethnicity as non-hispanic white, non-hispanic black, Asian, Hispanic, Pacific Islander or American Indian/Alaska Native (AI/AN) based on the USRDS designation (3). USRDS defines patient race and ethnicity based upon data obtained from the Medical Evidence Form (CMS 2728), the CMS Medicare Enrollment Database and the CMS Renal Management Information System/ Renal Beneficiary and Utilization System (REMIS/REBUS) identification file (3). Zip code-level covariates We included a variable for poverty based on US Census estimates of the percentage of residents living in poverty within the zip code where each patient resided at ESKD onset (<5%, 5 9%, 10 14%, 15 19% or 20% of the population) (18,19,27). The US Census defines a poverty area as an area where at least 20% of residents are poor (28). We further included a variable corresponding to the percentage of linguistically isolated households in each patient s zip code of residence (<1%, 1 4%, 5 9%, 10 19%, or 20% of the population). The US Census defines a linguistically isolated household as one in which all members aged 14 years and older speak a non- English language and also speak English less than very well (29). Statistical analysis We calculated mean crude rates of LDKT by race-ethnicity. We analyzed the associations of race-ethnicity and time to LDKT from ESKD onset using proportional hazards ( Cox ) regression. The referent group for all analyses was non-hispanic whites. To a base model comprising fixed, demographic factors (age, race-ethnicity and sex), we incorporated individual-level comorbid conditions, unhealthy behaviors (active tobacco smoking, alcohol dependence and drug abuse), body mass index, direct and indirect measures of access to nephrology (predialysis) care prior to ESKD (anemia, hypoalbuminemia, administration of predialysis erythropoiesis stimulating agent and receipt of predialysis nephrology care) and zip code-level proxies for contextual poverty and household linguistic isolation to examine their effects on the coefficient estimates for race-ethnicity. We used scaled Schoenfeld residual plots against time and estimated log ( log [survivor function]) versus time survival curves to assess the proportionality assumption and found no violations. We found no evidence of collinearity among the vector of explanatory variables using the variance inflation factor and Eigen values. To account for potential correlations due to practice patterns within OPO, we obtained robust sandwich estimates for the Cox model using the OPO as a cluster variable (30,31). We confirmed model fit using Cox-Snell residuals. To assess the degree of reduced or delayed LDKT attributable to measured demographic, clinical, socioeconomic and linguistic factors as well as regional deceased donor organ availability, we calculated the proportion of the reduced rate of transplantation for each racial-ethnic group (32). We performed bootstrap analyses (with 100 replications) to calculate the biascorrected confidence intervals of the hazard ratio estimates for LDKT by race-ethnicity. With bootstrapping, the data were randomly resampled to estimate the distribution of the variance (i.e. confidence intervals) in the hazard ratio estimate that occurred with the addition of a variable (or group of variables) to a multivariable model incorporating the covariates indicated above (33). To evaluate whether differences in LDKT rates were affected by differences in death rates (i.e. informative censoring), we repeated the main analyses using competing risks regression according to the method of Fine and Gray (34). These analyses, in which death was treated as a competing risk and end of study as administrative censoring, were adjusted for the same variables described above. The competing risk model provided an estimate of the rate of LDKT for patients while adjusting for differences in death rates by raceethnicity. To estimate the influence of differential rates of deceased donor 1558 American Journal of Transplantation 2013; 13:

3 Racial Determinants of Live Donor Kidney Transplant kidney transplantation (DDKT) on racial differences in LDKT, we performed additional analyses examining racial-ethnic differences in parameter estimates for any (i.e. either living or deceased) transplant. Finally, to examine the influence of preemptive transplantation and older age on the parameter estimates, we repeated all analyses in a reduced cohort of patients aged years that excluded patients who received preemptive transplants. We considered a two-tailed P-value <0.05 as statistically significant. All statistical analyses were conducted using Stata Statistical Software (Stata MP version 11.0, Stata Corp, College Station, TX). Results A total of adults aged years initiated treatment for ESKD in the United States during the study period. As expected, the distribution of health insurance coverage differed substantially according to race-ethnicity. The prevalence of employer group health coverage was highest among whites and Asians, and the prevalence of Medicaid enrollees and uninsured patients were highest among blacks, Hispanics and AI/ANs. In this cohort, the prevalence of diabetes was particularly high among Hispanics, Pacific Islanders and AI/ANs. Measures of high-quality predialysis care were invariably worse among most racial-ethnic minority groups as compared with whites (Table 1). The study population was distributed across residential zip codes in the United States with a high proportion of blacks, Hispanics and AI/ANs residing in areas of high poverty. Additionally, over half of Hispanics, over one-third of Asians and over one-quarter of Pacific Islanders lived in areas where 20% or more households were linguistically isolated compared with 6% of whites and 10% of blacks (Table 1). Time from ESKD onset to first LDKT Overall, subjects received a first LDKT during person-years. Mean rates of LDKT were lowest among blacks, AI/ANs and Pacific Islanders, intermediate among Hispanics and Asians, and highest among whites (Figure 1). In analyses adjusted for individual-level clinical factors and individual- and zip code-level sociodemographic factors, the lower transplant rates among racial-ethnic minority groups compared with whites were attenuated in all groups except among Asians (Tables 2 and 3). Race- or ethnicity-specific determinants of LDKT Among racial-ethnic minority groups, the degree to which reduced rates of LKDT were attributable to adjustment for measured factors varied significantly by race-ethnicity (Table 3). Among blacks and AI/ANs, the largest proportions of the disparity in LDKT compared with whites were attributed to adjustment for measures of predialysis care, while the largest proportion of the disparity among Hispanics compared with whites was attributed to adjustment for health insurance coverage. Substantial proportions of the disparity in transplant rates among blacks and AI/ANs compared with whites were attributed to adjustment for contextual poverty. Among all groups, there was little evidence that the disparity in LDKT compared with whites was attributable to household linguistic isolation. Further, differences in underlying comorbid conditions including diabetes and unhealthy behaviors accounted for little to none of the reduced rate of LDKT among all minority groups (Table 3). Differential rates of LDKT among racial-ethnic minority groups did not appear to result from racial-ethnic differences in rates of DDKT (Figure 1) or in competing rates of death (data not shown). In additional analyses that examined time to any transplant, disparities in transplant rates were slightly attenuated among black and Asian patients, and slightly worse among Hispanic, AI/AN and Pacific Islander patients (Table S1). Similar differences in LDKT by race-ethnicity were observed when patients who received a preemptive transplant and those older than 64 years were excluded (Table S2). In this reduced cohort of patients, the largest proportion of the disparity in LDKT among blacks and AI/ANs compared with whites was due to contextual poverty (11% and 17%, respectively), while the largest proportion (17%) among Hispanics compared with whites was attributed to health insurance coverage. As expected, the influence of predialysis care diminished when excluding patients who were preemptively transplanted. Discussion In this national study of US adults who initiated treatment for ESKD in recent years, we observed lower relative rates of LDKT among racial-ethnic minority as compared to white patients. In particular, black, AI/AN and Pacific Islander patients experienced age- and sex-adjusted rates of LDKT that were over 80% lower than white patients. Additionally, determinants (i.e. demographic, clinical, socioeconomic and linguistic) of reduced or delayed LDKT differed among racial-ethnic minority patients, as did the relative importance of these determinants in explaining variation in LDKT. We found that a large proportion of the reduced rate of LDKT among all racial-ethnic minority groups was attributable to differences in predialysis care measures. Suboptimal predialysis care may contribute to poor provider-patient and provider-family communication regarding the full range of treatment options. Limited communication during this critical phase prior to ESKD onset appears to associate with less knowledge about the benefits of LDKT and less willingness to accept nephrologists recommendations for transplantation (11,14). Improved predialysis care with timely LDKT communication and decision support may improve patients knowledge and consideration of LDKT (10,13). American Journal of Transplantation 2013; 13:

4 Purnell et al. Table 1: Characteristics of all US adult patients aged years who initiated treatment for ESKD during June 2005 to September 2008 by race-ethnicity Race or ethnicity Characteristic 1 White (N ¼ ) Black (N ¼ ) Asian (N ¼ 6 674) Hispanic (N ¼ ) Pacific Islander (N ¼ 1 953) American Indian/Alaska Native (N ¼ 2 576) Age, mean (SD), years 55.7 (11.3) 52.1 (11.8) 54.0 (12.2) 52.6 (12.4) 53.6 (11.5) 53.1 (11.3) Age category, %, years Female, % Health insurance coverage 2,% Employer group Medicare Medicaid No coverage Other coverage Clinical measures, % Diabetes CVD Poor functional status Tobacco use BMI 30 kg/m Predialysis access measures, % Nephrology care Prescribed ESA Hemoglobin <10 g/dl Serum albumin <3.5 g/dl Zip code-level: percentage of residents living in poverty, % <5% % % % % Zip code-level: percentage of linguistically isolated households, % <1% % % % % Due to rounding, percentages may not total 100% for some categories. 2 Health insurance coverage may sum to >100% in patients with multiple sources of coverage. 3 Cardiovascular disease. In addition to predialysis care measures, we found that contextual poverty was an important determinant of differences in LDKT rates for most minority groups, particularly black and AI/AN patients. This observation is consistent with previous findings, which suggest that patients living in neighborhoods with higher degrees of poverty may be less likely to receive transplants than patients living in more affluent areas (19,22). Patients living in areas with a higher degree of poverty may be more likely to encounter geographic and socioeconomic barriers including resource deprivation and financial disincentives to completing the required steps needed to facilitate successful LDKT (7,35). Clustering of risk factors for chronic kidney disease (CKD) and other clinical comorbidities within impoverished areas may also reduce the potential living donor pool for patients residing in poor as compared with more affluent areas (15,18). A significant proportion of the reduced rate of LDKT among black, Hispanic and AI/AN patients was also attributable to differences in health insurance coverage. While the US ESKD Medicare program provides health insurance 1560 American Journal of Transplantation 2013; 13:

5 Racial Determinants of Live Donor Kidney Transplant LDKT White Asian Hispanic AI/AN Black Pacific Islander DDKT White Asian Hispanic Black AI/AN Pacific Islander coverage for the vast majority of patients after initiation of renal replacement therapy, these benefits do not extend to many patients in earlier stages of CKD (3,36). Reduced health care access due to suboptimal health insurance coverage and poor availability or utilization of routine medical care in earlier stages of CKD may result in delayed nephrology care and fewer preemptive referrals for Event rate per 100 person-years Figure 1: Mean unadjusted rates (per 100 person-years) of living (LDKT) and deceased (DDKT) donor kidney transplant by race-ethnicity. Error bars represent the 95% confidence interval for the point estimate. transplantation. These delays in turn could result in lower rates of transplant evaluations, higher rates of incomplete workups and reduced access to transplantation (23). In contrast with the other minority groups, we found relatively few determinants of the reduced rate of LDKT among Asian patients. Asians tend to reside in distinct regions of the United States where local community (e.g. access to transplant programs) and cultural factors may limit pursuit of LDKT even in the presence of adequate health insurance coverage and community resources. Somewhat paradoxically, we found little evidence that delayed LDKT among Asians, Pacific Islanders and Hispanics relative to whites was attributable to household linguistic isolation. While patients residing in linguistically isolated households might encounter difficulty understanding and navigating the transplant process, it is plausible that the increased availability of interpreters and educational materials on LDKT in diverse languages has reduced the relative influence of these factors (37). It is also possible that area-level measures of household linguistic isolation are relatively insensitive proxies for patients who encounter linguistic challenges during the LDKT process. Furthermore, the substantial residual disparity in LDKT by raceethnicity after extensive adjustment for measured factors suggests a potential role of cultural factors. Previous work among black and Hispanic patients reported that distinct cultural barriers may limit the ability of medical providers to understand their patients values and cultural beliefs, which influence preferences for LDKT (10,38,39). Future efforts are needed to more comprehensively address these barriers and to identify impediments to LDKT among less well-studied groups, such as Asians and Pacific Islanders. While prior research has reported that blacks and other racial-ethnic minorities are less likely to undergo LDKT (6,8), our study uniquely and comprehensively examines the relative influence of race-ethnicity-specific, patient-, and Table 2: Hazard ratios for race-ethnicity and time from ESKD onset to live-donor kidney transplantation among adults aged years with incident ESKD during June 2005 to September 2008 Race or ethnicity At-risk (N ¼ ) LDKT events (n ¼ ) Rate per 100 person-years (95% CI) LDKT events biological donors, N (%) Model 1 HR (95% CI) Model 2 HR (95% CI) White ( ) 3974 (54) 1.00 (Ref.) 1.00 (Ref.) Black ( ) 735 (63) 0.16 (0.15, 0.17) 0.27 (0.24, 0.31) Asian ( ) 206 (57) 0.56 (0.51, 0.63) 0.48 (0.40, 0.57) Hispanic ( ) 791 (67) 0.33 (0.31, 0.35) 0.58 (0.54, 0.62) Pacific Islander ( ) 20 (63) 0.19 (0.15, 0.26) 0.23 (0.15, 0.33) AI/AN ( ) 35 (68) 0.19 (0.14, 0.28) 0.42 (0.29, 0.60) Model 1: Adjusted for age, sex and race-ethnicity. Model 2: Adjusted for age, sex, race-ethnicity, health insurance coverage (employer group insurance, Medicare, Medicaid, other insurance or no insurance), clinical factors [cardiovascular disease, chronic lung disease, diabetes, poor functional status (inability to walk, inability to transfer), body mass (Quetelet s) index, drug abuse, alcohol dependence or tobacco use], predialysis access measures [serum albumin concentration, hemoglobin level, nephrology care and prescribed erythropoiesis stimulating agent], zipcode poverty, zipcode linguistic isolation and OPTN/UNOS region. American Journal of Transplantation 2013; 13:

6 Purnell et al. Table 3: Hazard ratio estimates for time from ESKD onset to live donor kidney transplantation among adults aged years with incident ESKD during Variable Hazard ratio 95% CI Age Age squared Sex Male Referent Referent Female Health insurance coverage Employer group Referent Referent Medicare Medicaid No coverage Other coverage Race-ethnicity White Referent Referent Black Asian Hispanic Pacific Islander American Indian/Alaska Native Clinical measures Diabetes CVD Poor functional status Chronic lung disease Tobacco use Drug use Alcohol dependence BMI BMI squared Predialysis access measures Predialysis nephrology care Albumin Hemoglobin Prescribed ESA Zip-code poverty <5% Referent Referent 5 9% % % % Household linguistic isolation <1% Referent Referent 1 4% % % % Estimates are from multiply imputed hierarchical models that are clustered on the Organ Procurement Organization. area-level factors in explaining variation in LDKT among all major US racial-ethnic groups of patients initiating ESKD treatment. Previously, Weng et al. observed that black kidney transplant candidates at a single transplant center were less likely to receive LDKTs due to lower rates of donor recruitment and conversion (8). Additionally, Gore et al. found that older age, less education, zip code-level income and Medicare insurance coverage were associated with overall lower odds of receiving LDKT among US adults undergoing primary kidney transplantation during (6). Our study findings extend those of prior work by identifying race-ethnicity-specific factors that significantly contributed to delays in LDKT among all major US racialethnic groups (including less well-studied groups, such as Asians, Pacific Islanders and AI/ANs) and by quantifying the contribution of these factors to delayed LDKT. Our findings may guide the development of interventions designed to more specifically address racial-ethnic disparities in LDKT. Based on our results, efforts to expand health insurance coverage in earlier stages of CKD, to improve access to high-quality predialysis care, and to overcome socioeconomic barriers to LDKT are particularly important to address racial-ethnic disparities in LDKT. For example, area-level studies that examine the distribution and quality of care within CKD clinics, particularly those that serve racial-ethnic minority communities, may provide valuable insight on how (and whether) expansion of health insurance coverage might change access to high-quality predialysis care for racial-ethnic minority groups. Similarly, studies that incorporate social workers and financial counselors into LDKT educational efforts have reported early success in reducing patients financial concerns regarding the LDKT process (40). However, the impact of such interventions on subsequent progress through the LDKT process has yet to be established. Lastly, the large residual disparity after extensive covariate adjustment warrants continued development of culturally-sensitive, literacy-appropriate LDKT education interventions and formal testing of their effects on patient-centered decision-making. Such decision-making would ideally incorporate patient and family engagement in ESKD treatment options while respecting cultural factors, such as cultural norms, preferences and values (41,42). Our study has a number of strengths including analysis of a well-characterized national population of adult patients who initiated ESKD treatment and comprehensive follow-up for kidney transplantation and death. We also included comparative data for racial-ethnic groups that have been historically understudied with respect to LDKT (i.e. Asians, Hispanics, Pacific Islanders, AI/ANs). Our study also has several potential limitations. First, we based our assessment of race-ethnicity on provider-reported data obtained from the CMS medical evidence records, which has the potential for misclassification. However, the direction and magnitude of our results align with those from other studies in kidney transplantation, some of which were based on self-reported ethnicity, and thus we suspect that the impact of this bias, if present, was likely small. Second, measures of poverty and linguistic isolation were only available at the zip-code level. Therefore, we were unable to control for individual-level income and linguistic isolation, which may differ from zip-code level measures. While contextual poverty may not comprehensively reflect an individual patient s financial resources for undertaking the LDKT process, it serves as an important community-level proxy 1562 American Journal of Transplantation 2013; 13:

7 Racial Determinants of Live Donor Kidney Transplant Table 4: Percentage (95% CI) of race-ethnicity effect attributed to adjustment for patient and area-level determinants of live-donor kidney transplantation among adults aged years who initiated treatment for ESKD during Race-ethnicity White (N ¼ ) Black (N ¼ ) Asian (N ¼ 6674) Hispanic (N ¼ ) Pacific Islander (N ¼ 1953) American Indian/Alaska Native (N ¼ 2576) Race-ethnicity effect attributed to adjustment for Zip code/contextual poverty Percent (95% CI) 15.7 (13.8, 17.5) 7.0 ( 8.2, 5.8) 3.7 (2.6, 4.7) 6.2 (4.1, 8.4) 18.1 (17.2, 19.1) Health insurance coverage Percent (95% CI) 10.2 (9.1, 11.6) 1.3 (0.4, 3.5) 17.1 (15.7, 19.9) 0.2 ( 4.0, 2.9) 8.3 (3.5, 14.5) Predialysis care measures (receipt of nephrology care and/or ESA, hypoalbuminemia, anemia) Percent (95% CI) 20.4 (19.5, 22.9) 7.6 (4.5, 9.7) 14.4 (12.2, 16.4) 12.2 (5.3, 18.6) 28.7 (21.1, 35.2) Differences in body size and diabetes status Percent (95% CI) 0.3 ( 0.3, 1.0) 9.3 ( 10.7, 8.3) 1.9 ( 3.2, 1.1) 2.1 ( 4.4, 1.6) 1.4 ( 0.7, 2.4) Household linguistic isolation Percent (95% CI) 1.0 ( 1.8, 0.1) 5.5 ( 7.7, 2.4) 3.6 (0.8, 6.5) 1.9 ( 1.8, 6.1) 2.6 (0.7, 3.7) Underlying comorbid conditions (cardiovascular disease, chronic lung disease, functional status) Percent (95% CI) 2.2 ( 2.8, 1.6) 4.5 ( 5.4, 3.5) 3.4 ( 4.1, 2.7) 1.6 ( 3.3, 1.1) 3.4 ( 5.1, 1.3) Unhealthy behaviors (alcohol dependence, tobacco or drug use) Percent (95% CI) 1.4 ( 1.8, 0.9) 3.8 ( 4.4, 3.1) 3.7 ( 4.2, 3.2) 2.9 ( 3.9, 1.4) 0.7 ( 0.4, 2.5) Negative values indicate that, after adjustment for the specific factors, differences in time to LDKT compared with whites were larger than observed in the age-, sex- and race-adjusted models. for geographic and socioeconomic barriers to care (16). Third, our results are potentially limited by under-reporting of several measures, such as patient comorbid medical conditions and receipt of predialysis nephrology care (43). However, given the magnitude of racial-ethnic differences in relative LDKT attainment, it seems unlikely that observed differences in LDKT were caused by residual confounding from differential ascertainment of comorbidities or predialysis nephrology care alone. Fourth, the shortened follow-up period for patients who initiated ESKD treatment in 2008 may have precluded identification of a living donor. Although we observed similar estimates when restricting the analyses to patients who initiated treatment during , extending the follow-up period for these patients may have allowed us to further refine our estimates. Finally, we were unable to account for other individual- or center-level characteristics (e.g. cultural attitudes, disparities in provision of transplant education) that might contribute to disparities in LDKT (44), as many patients had yet to list or select a specific transplant center. A recent report observed that black patients were less likely to receive LDKT at every transplant center in the United States, but that this disparity was attenuated in centers with higher rates of kidney transplants (45). Despite two decades of recognition, we found that relative rates of LDKT remain substantially lower among racialethnic minority patients as compared with white counterparts. However, determinants of delayed LDKT differed according to race-ethnicity. Black, Hispanic and AI/AN patients face persistent difficulty in accessing LDKT due to American Journal of Transplantation 2013; 13: socioeconomic factors and limited health insurance coverage. In contrast with other minority groups, few measured determinants including household linguistic isolation appeared to explain low rates of LDKT among Asian patients. Differences in measures of predialysis care contributed substantially to delayed LDKT among all racial ethnic minority groups. Geographically targeted efforts to address these important determinants of delayed LDKT may help to reduce pervasive racial-ethnic differences in kidney transplantation in the United States. Acknowledgments Dr. Purnell was supported by grant F31DK from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). Dr. Hall was supported by grant K23DK from the NIDDK of the NIH and the Norman Coplon extramural grant program of Satellite Healthcare. Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. References 1. Cecka M. Clinical outcome of renal transplantation. Factors influencing patient and graft survival. Surg Clin North Am 1998; 78:

8 Purnell et al. 2. Jofre R, Lopez-Gomez JM, Moreno F, Sanz-Guajardo D, Valderrabano F. Changes in quality of life after renal transplantation. Am J Kidney Dis 1998; 32: U.S. Renal Data System, USRDS Annual data report: Atlas of chronic kidney disease and end-stage renal disease in the united states, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, Eggers PW. Racial differences in access to kidney transplantation. Health Care Financ Rev 1995; 17: Agency for Healthcare Research and Quality National healthcare disparities report. Rockville, MD: U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality; March AHRQ Pub. No Gore JL, Danovitch GM, Litwin MS, Pham PT, Singer JS. Disparities in the utilization of live donor kidney transplantation. Am J Transplant 2009; 9: Purnell TS, Hall YN, Boulware LE. Understanding and overcoming barriers to living kidney donation among racial and ethnic minorities in the United States. Adv Chronic Kidney Dis 2012; 19: Weng FL, Reese PP, Mulgaonkar S, Patel AM. Barriers to living donor kidney transplantation among black or older transplant candidates. Clin J Am Soc Nephrol 2010; 5: Alvaro EM, Siegel JT, Turcotte D, Lisha N, Crano WD, Dominick A. Living kidney donation among Hispanics: A qualitative examination of barriers and opportunities. Prog Transplant 2008; 18: Boulware LE, Meoni LA, Fink NE, et al. Preferences, knowledge, communication, and patient physician discussion of living kidney transplantation in African American families. Am J Transplant 2005; 5: Waterman AD, Stanley SL, Covelli T, Hazel E, Hong BA, Brennan DC. Living donation decision making: Recipients concerns and educational needs. Prog Transplant 2006; 16: Rodrigue JR, Cornell DL, Kaplan B, Howard RJ. A randomized trial of a home-based educational approach to increase live donor kidney transplantation: Effects in blacks and whites. Am J Kidney Dis 2008; 51: Boulware LE, Hill-Briggs F, Kraus ES, et al. Identifying and addressing barriers to African American and non-african American families discussions about preemptive living related kidney transplantation. Prog Transplant 2011; 21: Kinchen KS, Sadler J, Fink N, et al. The timing of specialist evaluation in chronic kidney disease and mortality. Ann Intern Med 2002; 137: Freedman BI, Spray BJ, Tuttle AB, Buckalew VM. The familial risk of end-stage renal disease in African Americans. Am J Kidney Dis 1993; 21: Hall YN, O Hare AM, Young BA, Boyko EJ, Chertow GM. Neighborhood poverty and kidney transplantation among US Asians and Pacific Islanders with end-stage renal disease. Am J Transplant 2008; 8: Clark CR, Hicks LS, Keogh JH, Epstein AM, Ayanian JZ. Promoting access to renal transplantation: The role of social support networks in completing pre-transplant evaluations. J Gen Intern Med 2008; 23: Volkova N, McClellan W, Klein M, et al. Neighborhood poverty and racial differences in ESRD incidence. J Am Soc Nephrol Feb 2008; 19: Patzer RE, Amaral S, Wasse H, Volkova N, Kleinbaum D, McClellan WM. Neighborhood poverty and racial disparities in kidney transplant waitlisting. J Am Soc Nephrol 2009; 20: Hall YN, Sugihara JG, Go AS, Chertow GM. Differential mortality and transplantation rates among Asians and Pacific Islanders with ESRD. J Am Soc Nephrol 2005; 16: Young CJ, Gaston RS. African Americans and renal transplantation: Disproportionate need, limited access, and impaired outcomes. Am J Med Sci 2002; 323: Sequist TD, Narva AS, Stiles SK, Karp SK, Cass A, Ayanian JZ. Access to renal transplantation among American Indians and Hispanics. Am J Kidney Dis 2004; 44: Kasiske BL, Snyder JJ, Matas AJ, Ellison MD, Gill JS, Kausz AT. Preemptive kidney transplantation: The advantage and the advantaged. J Am Soc Nephrol 2002; 13: Cass A, Cunningham J, Snelling P, Ayanian JZ. Late referral to a nephrologist reduces access to renal transplantation. Am J Kidney Dis 2003; 42: World Health Organization. Global database on body mass index. BMI Classification. ¼intro_3.html. Last accessed September U.S., Organ Procurement and Transplantation Network. Department of Health and Human Services, Health Resources and Services Administration, Rockville, MD; United Network for Organ Sharing, Richmond, VA; Available at gov. Last accessed December Krieger N. Overcoming the absence of socioeconomic data in medical records: Validation and application of a census-based methodology. Am J Public Health 1992; 82: United States Census Bureau. Statistical Brief. Poverty Areas. html. Last accessed July United States Census Bureau. Housing Patterns. Racial and ethnic residential segregation in the United States: Last accessed July Lin DY, Wei LJ. The robust inference for the Cox proportional hazards model. J Am Statist Assoc 1989; 84: Williams RL. A note on robust variance estimation for clustercorrelated data. Biometrics Jun 2000; 56: Freedman LS, Graubard BI, Schatzkin A. Statistical validation of intermediate endpoints for chronic diseases. Stat Med Jan ; 11: Efron B, Tibshirani RJ. An Introduction to the Bootstrap. Chapman & Hall/CRC Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Statist Assoc 1999; 94: Clarke KS, Klarenback S, Vlaicu S, Yang RC, Garg AX. The direct and indirect economic costs incurred by living kidney donors A systematic review. Nephrol Dial Transplant 2006; 21: Hall YN, Rodriguez RA, Boyko EJ, Chertow GM, O Hare AM. Characteristics of uninsured Americans with chronic kidney disease. J Gen Intern Med 2009; 24: Gordon EJ, Caicedo JC, Ladner DP, Reddy E, Abecassis MM. Transplant center provision of education and culturally and linguistically competent care: A national study. Am J Transplant 2010; 10: Callender CO, Miles PV, Hall MB. National MOTTEP: Educating to prevent the need for transplantation. Minority Organ Tissue Transplant Education Program. Ethn Dis 2002; 12: S Siegel JT, Alvaro EM, Lac A, Crano WD, Dominick A. Intentions of becoming a living organ donor among Hispanics: A theory-based approach exploring differences between living and nonliving organ donation. J Health Commun 2008; 13: Lunsford SL, Shilling LM, Chavin KD, et al. Racial differences in the living kidney donation experience and implications for education. Prog Transplant 2007; 17: American Journal of Transplantation 2013; 13:

9 Racial Determinants of Live Donor Kidney Transplant 41. Beach MC, Saha S, Cooper LA. The role and relationship of cultural competence and patient-centeredness in health care quality. The Commonwealth Fund, Report Dy S, Purnell TS. Key concepts relevant to quality of complex and shared decision making in health care: A literature review. Soc Sci Med : Kim JP, Desai M, Chertow GM, Winkelmayer WC. Validation of reported predialysis nephrology care of older patients initiating dialysis. J Am Soc Nephrol 2012; 23: Kucirka LM, Grams ME, Balhara KS, Jaar BG, Segev DL. Disparities in provision of transplant information affect access to kidney transplantation. Am J Transplant 2012; 12: Hall EC, James NT, Garonzik-Wang JM, et al. Center-level factors and racial disparities in living donor kidney transplantation. Am J Kidney Dis 2012; 59: Supporting Information Additional Supporting Information may be found in the online version of this article at publisher s web site: Table S1. Comparison of hazard ratios for LDKT versus any transplant. Table S2. Comparison of hazard ratios for LDKT of full cohort versus reduced cohort (excluding preemptively transplanted patients and patients 65 years and older). American Journal of Transplantation 2013; 13: