Association of Race and Age With Survival Among Patients Undergoing Dialysis FREE

Blacks are significantly overrepresented in the end-stage renal disease (ESRD) population. Of more than 500 000 individuals with ESRD in the United States, approximately one-third are black, and the relative incidence of ESRD is 3.6 times higher among black than white patients.¹ Moreover, racial disparities in quality of and access to care for patients with kidney disease are well-documented.^2- 4 Compared with white patients, fewer black patients with chronic kidney disease (CKD) are under the care of a nephrologist, and their rates of referral for peritoneal dialysis and kidney transplantation are significantly lower.^5- 6 Black patients who receive dialysis are less likely to receive an adequate dialysis dose,^7- 8 have a fistula placed,^9- 10 and achieve target hemoglobin levels—all metrics associated with decreased dialysis survival.¹¹

Despite the disparity in care, current thinking, supported by more than 30 previous studies, is that black patients receiving dialysis survive longer than their white counterparts.^{2- 3,8,12- 42} Black patients with ESRD are reported to have 13% to 45% lower mortality when receiving dialysis than their white counterparts, a finding that persists in both unadjusted analysis and after adjustment for comorbidities and socioeconomic status. Varying postulations for this counterintuitive observation have included differential sensitivity to dialysis dose,⁸ racial differences in nutritional status, or racial differences in inflammation³⁹—the biological or sociological mechanisms for which remain unclear. Moreover, the perception of enhanced dialysis survival seems to have affected clinical decision making and engendered complacency about the low rates of transplantation among black patients.^2,43 Although kidney transplantation is the preferred form of renal replacement therapy regardless of race, black patients have lower rates of transplant referral and longer dialysis vintage at referral than their white counterparts.^5,44- 49

The paradox of enhanced dialysis survival in the setting of decreased access to care may be in part a byproduct of study design. Population-based studies of dialysis survival can mask important subgroup effects, particularly given that the majority of dialysis patients are older than 65 years.¹ As such, studies of the dialysis population as a whole are dominated by effects among older adults,⁵⁰ in which disparities in access to care are attenuated by Medicare eligibility. In fact, racial disparities in CKD mortality occur almost exclusively among younger age groups,⁵¹ as do inequities in access to transplantation.⁵²

Given the hypothesis that disparities in socioeconomic status and insurance coverage are likely greatest in younger ESRD patients, and that these disparities are manifest both in rates of transplantation and dialysis mortality, the goals of this study were (1) to examine age as an effect modifier of the racial disparities in dialysis survival, and (2) to determine if differential rates of kidney transplantation modify the risk of death in dialysis patients.

The study cohort included 1 330 007 adults, identified as either African American/black (n = 407 140) or Caucasian/white (n = 922 867), as indicated on the Centers for Medicare & Medicaid Services (CMS) 2728 Medical Evidence Form, signed and filed for each patient by the supervising physician within 45 days of dialysis initiation or transplant. All patients initiated dialysis or received a predialysis transplant for the first time between January 1, 1995, and September 28, 2009.

Data were drawn from the United States Renal Data System, a national registry of all ESRD patients in the United States. Patients were observed from ESRD diagnosis until death, which was ascertained via linkage to the Social Security Master Death File. The presence or absence of 18 major comorbidities and 2 physical impairments was captured via a checklist on the CMS 2728 Medical Evidence Form. All patients were observed until death, kidney transplantation, or end of study (September 28, 2009). Comorbidity status was ascertained at ESRD onset; only joining the waitlist, receiving a kidney transplant, and occurrence of death were measured longitudinally. Rates of death and transplantation are high in this population; as such, outcomes for many patients occurred soon after ESRD onset and the median follow-up time (time from ESRD onset to first noted event) was 21.5 months (range, 1 day-14.8 years). However, the median potential follow-up time (time from ESRD onset to end of study) was 6.7 years. This study was reviewed by the institutional review board at Johns Hopkins School of Medicine and determined to qualify for an exemption under the Code of Federal Regulations, Protection of Human Subjects (45 CFR 46.101[b]) as study participants cannot be identified directly or through linked identifiers.

In order to replicate previous studies, a multivariate Cox proportional hazards model, including patients of all ages, was adjusted for the following factors: age, race (black vs white), sex, insurance type at ESRD onset, body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), cause of ESRD, predialysis or pretransplant erythropoietin administration (a surrogate for having nephrology care prior to ESRD onset), atherosclerotic heart disease, cardiac failure, peripheral vascular disease, cerebrovascular disease, hypertension, diabetes, smoking, immobility, malignant neoplasm/cancer, chronic obstructive pulmonary disease, drug dependence, alcohol dependence, and dialysis type (peritoneal or hemodialysis). Patients were censored at transplantation or end of study.

The cohort was then stratified by age, and dialysis survival among black and white patients was compared using Cox proportional hazards models (adjusted for the factors listed previously). As with the population-based survival analysis, patients were censored at transplantation or end of study. To confirm whether differences between age groups were statistically significant, an additional model was built including interaction terms for each age category and black race.

To account for age-stratified differences in transplant rates between black and white patients, the same analyses were repeated using competing risk regression according to the methods of Fine and Gray.⁵³ These models, in which transplantation was treated as a competing risk and end of study as administrative censoring, provided an estimate of the risk that those who start dialysis will die while on dialysis. In other words, while the Cox model better estimated the risk of death if black and white patients underwent transplantation at equal rates (adjusted hazard ratio [aHR]), the competing risk model better estimated the risk of death on dialysis for patients given the current disparities in access to transplantation (adjusted subhazard ratio [aSHR]).

To further explore those patients in whom disparities of the highest magnitude were identified, dialysis survival among additional subgroups within the 18- to 30-year range were explored by sex, insurance, BMI, type of dialysis, erythropoietin use, and reported primary cause of ESRD to determine whether racial disparities persisted across all or were specific to certain subgroups of younger patients.

All analyses were performed by using multiprocessor Stata version 11.0/MP for Linux (StataCorp, College Station, Texas). All hypothesis tests were 2-sided, with statistical significance defined as having a P value of less than .05.

Among 1 330 007 incident ESRD patients between 1995 and 2009, black patients were on average younger (58.1 years vs 64.5 years). Although black patients aged 18 to 30 years had rates of comorbid conditions similar to white patients, those older than age 30 years were less likely to have atherosclerotic heart disease (6.7% vs 10.9% for age 31-50 years; 20.6% vs 34.1% for those older than age 50 years) and peripheral vascular disease (4.7% vs 8.4% for age 31-50 years; 12.3% vs 18.6% for those older than age 50 years), and those older than age 50 years were less likely to have cardiac failure (33.5% vs 38.8%) and chronic obstructive pulmonary disease (6.2% vs 11.3%) and more likely to have hypertension (88.6% vs 81.8%, Table 1). Of incident ESRD patients of all ages entering the study, 57.1% of black and 63.5% of white patients died as dialysis recipients, and 9.1% of black and 12.4% of white patients received kidney transplants, with 25.7% of transplants in black patients provided from live donors compared with 42.8% in white patients (Figure 1). Adjusting for differences in demographics and comorbidities, and censoring for transplantation, black patients had a lower risk of death as dialysis recipients than white patients (aHR, 0.84; 95% CI, 0.83-0.84; P <.001).

However, the relationships between race, dialysis survival, and transplantation were substantially modified by patient age, with opposite inferences in the younger age groups. Among 18- to 30-year-olds with incident ESRD entering the study, 27.6% of black and 14.2% of white patients died as dialysis recipients, and 31.9% of black and 54.9% of white patients received transplants (Figure 1). In adjusted models specific to this age group, black patients had a higher risk of death as dialysis recipients censoring for transplantation (aHR, 1.44; 95% CI, 1.37-1.51; Figure 2) and treating transplantation as a competing event (aSHR, 1.93; 95% CI, 1.84-2.03; Figure 2).

Similarly, among 31- to 40-year-olds with incident ESRD entering the study, 37.4% of black and 26.8% of white patients died as dialysis recipients, and 20.5% of black and 45.1% of white patients received transplants (Figure 1). In adjusted models specific to this age group, black patients had a higher risk of death as dialysis recipients censoring for transplantation (aHR, 1.10; 95% CI, 1.06-1.13) and treating transplantation as a competing event (aSHR, 1.46; 95% CI, 1.41-1.50; Figure 2).

Subgroup estimates specific to older patients were very similar to population-based estimates previously reported in the literature. For example, among individuals aged 61 to 70 years entering the study, 64.9% of black and 67.2% of white patients died as dialysis recipients, and 4.2% of black and 7.8% of white patients received transplants (Figure 1). In adjusted models specific to this age group, black patients had a lower risk of death as dialysis recipients censoring for transplantation (aHR, 0.81; 95% CI, 0.80-0.82) and treating transplantation as a competing event (aSHR, 0.87; 95% CI, 0.86-0.88; Figure 2). In a model including interaction terms for race and each age category, all interaction terms were statistically significant, confirming differences in the race disparity between age subgroups (P <.05 for all).

The age subgroup with the highest disparity in risk of death between black and white dialysis patients was that of 18- to 30-year-olds. As such, further exploration of this subgroup was performed to better understand potential mechanisms for the marked difference in racial disparities among younger patients. In the 18- to 30-year-old subgroup, black patients were less likely to have private insurance (22.1% vs 33.8%), more likely to have Medicaid or no insurance (67.1% vs 51.4%), more likely to have hypertension as the primary cause of renal failure (27.6% vs 11.2%), and less likely to receive erythropoietin (21.4% vs 30.1%). Rates of other comorbidities were similar by race (Table 1). Further stratification of 18- to 30-year-olds by clinically important subgroups showed that the disparity for black patients persisted across all with the exception of those with a BMI of 35 or higher (aHR, 1.09; 95% CI, 0.94-1.26) and those with diabetes as the primary cause of ESRD (aHR, 1.02; 95% CI, 0.93-1.11). In a competing risk analysis, a substantial survival disparity persisted across all subgroups (Table 2).

In this national study of dialysis survival among 1 330 007 incident ESRD patients, we have shown that the commonly cited survival advantage for black patients undergoing dialysis applies only to those older than 50 years of age. In marked contrast, younger black patients have as much as twice the hazard of death as dialysis recipients compared with their white counterparts, even after adjusting for many demographic factors and comorbidities. Additionally, the disparity in younger patients widens when the differential rates of kidney transplantation for black and white patients are considered in a competing risk analysis.

Our population-based results are consistent with many earlier studies,^{2- 3,8,12- 42} supporting face validity of our study cohort and analytical approach. However, the demonstration of significant age-based effect modification of the racial differences in dialysis survival is novel, challenging conventional wisdom and identifying a significant disparity among younger black patients that needs to be addressed. The finding of increased mortality among younger black ESRD patients is consistent with previous findings among the general population and in those with CKD but not yet ESRD.³⁵

The majority of dialysis patients are older than 65 years of age, so inferences from population-based models are driven by this subgroup and may not be generalizable to patients of all ages. Younger patients may be fundamentally different from older patients in the prevalence of comorbidities, socioeconomic status, and the underlying biology of disease. Furthermore comorbidities and socioeconomic status disparities likely influence outcomes of younger and older adults differentially. Previous studies have shown that age modifies race and sex disparities in transplant patients.^50,52,54 Likewise, this study has shown that inferences about survival of dialysis patients drawn from the entire population, in this case that black patients have a lower death rate as dialysis recipients than their white counterparts, do not apply to younger patients. Assuming that population-based inferences are generalizable to subgroups within the population has the potential to mislead clinical decision making. Furthermore, while older black patients have better survival as dialysis recipients compared with older white patients, it is important to note that patients of all ages and races derive a survival benefit from transplantation vs remaining on dialysis.⁵⁵

Additionally, accounting for transplant as a competing risk brings to light an even greater disparity in death on dialysis in younger age groups in which transplant is most common and racial disparities in access are greatest.⁵² Use of this method allows us to infer that the 2-fold increased hazard of death on dialysis in younger black patients is composed of 2 distinct components: one of differential rates of transplantation and one of biology (or some interaction between biology and socioeconomic factors). Blacks are much less likely to receive a transplant from a live donor; as such interventions to reduce transplant disparities should prioritize the improvement of live donation rates for blacks.

One potential contributor to the significant racial disparity among younger adults, but not older adults, is insurance coverage: young black patients are more likely to be uninsured (or Medicaid insured) than young white patients, while all older adults are Medicare eligible. As hypothesized, disparity in insurance is greater among the younger ESRD population; however, even among those with private insurance, young black patients had a higher risk of death as dialysis recipients than their white counterparts. And even among young patients with previous erythropoietin stimulating agent use, a proxy for medical care during CKD progression, young black dialysis patients experienced a higher risk of death. It is likely, then, that any socioeconomic contributors to this disparity remain uncharacterized or unmeasured.

Several limitations merit consideration. First, only patients who survived long enough to develop ESRD were captured, and therefore the impact of differential mortality for black dialysis patients in earlier stages of CKD survival could not be quantified. Black patients with CKD die at a higher rate than their white counterparts, possibly causing a survivor bias in which the black patients who survive to ESRD are healthier than white patients who survive to ESRD. Without linkage of CKD data to the United States Renal Data System registry, we were unable to quantify the effects of this survival bias.

Second, comorbidity data captured in the CMS 2728 Medical Evidence Form is coded as presence or absence of disease, and nuances of severity of comorbidities could not be considered. However, the CMS 2728 Medical Evidence Form does provide a rich source of comorbidity information, and this comorbidity ascertainment was adequate to demonstrate consistency between our initial population-based analyses and previous literature.

In summary, this study challenges the widespread notion that black patients undergoing dialysis survive longer than their white counterparts. Despite a survival advantage in older age groups, black patients younger than 50 years are at substantially increased risk of death as dialysis recipients. Inequities in dialysis survival are compounded by inequities in access to transplantation. Determining why younger black patients are at increased risk of death as dialysis recipients is critical in order to improve clinical decision making and inform policies aimed at achieving equity in ESRD care.