Similar Outcomes among Black and White Renal Allograft Recipients

RESULTS

There were 26,098 incident dialysis patients in this study, representing a random sample of approximately 75% of all patients initiating dialysis in Canada during the study period. Of these, 3459 (13%) were of neither black nor white race and 2396 (9%) were of unknown race and were therefore excluded. All analyses were performed on the remaining 20,243 individuals, 3% were black of whom of whom and 97% of whom were white (Table 1). By study end, 12,409 (61%) died before receiving a transplant and 214 (1%) were lost to follow-up. Black patients were significantly more likely than white patients to have diabetic nephropathy listed as their primary renal disease (37 versus 27%). Among comorbid conditions, coronary disease was significantly higher among white compared with black patients (33 versus 24%), as was current smoking status (15 versus 6%). Black patients were significantly more likely to be in the lowest quintile of socioeconomic stats (SES; 38 versus 23%).

During the study period, 5036 individuals underwent kidney transplantation. Table 2 presents the relative rates of renal transplantation by black versus white race. After adjustment, black patients were significantly less likely to receive a renal transplant (deceased and living donor combined) when compared with white patients (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.51 to 0.69; P < 0.0001). The difference between black and white patients seemed to be less pronounced for deceased as compared with living donors. The interaction between race and age and between race and diabetes status was significant (P < 0.0001 and P = 0.005, respectively), suggesting that it would be appropriate to present the rate of transplantation after stratification by age and diabetes status.

For patients aged <40 yr, black patients had a 51% lower rate of transplantation as compared with white patients (HR 0.49; 95% CI 0.38 to 0.62; P < 0.0001), whereas those in the 50.0- to 59.9-yr age group had a 41% lower rate than comparably aged white patients (HR 0.59; 95% CI 0.42 to 0.82; P = 0.002). Among those aged ≥60 yr, the rate of transplantation was nonsignificantly higher for black than for white patients (HR 1.47; 95% CI 0.97 to 2.23; P = 0.07. Among those with diabetes, there was no significant difference in the rate of renal transplantation for black compared with white patients (HR 0.90; 95% CI 0.66 to 1.22; P = 0.50); however, among those without diabetes, black patients had a significantly lower rate of transplantation compared with white patients (HR 0.57; 95% CI 0.48 to 0.67; P < 0.001).

Table 3 compares the characteristics of black and white transplant recipients during the study period. Of these 5036 patients, 4841 (96%) were white and 195 (4%) were black. Overall, differences between black and white transplant recipients were similar to those in the general dialysis population. For example, black renal transplant patients were slightly younger, more often lived in lower income urban communities, and were significantly more likely than white patients to have hypertensive/ischemic nephropathy as their primary renal diagnosis.

Table 4 compares transplant outcomes between black and white patients. The median follow-up time among transplant recipients was 5.2 yr; 857 (15%) experienced graft failure, death occurred in 641 (13%) of patients, and 14 (0.3%) were lost to follow-up. In this analysis, there was no significant difference in the adjusted rate of graft failure between black and white patients (HR 1.16; 95% CI 0.82 to 1.64; P = 0.40) or the adjusted rate of graft failure or death (HR 0.90; 95% CI 0.67 to 1.21; P = 0.48; Table 4). After adjustment, black transplant recipients had significantly lower posttransplantation mortality compared with white patients (HR 0.49; 95% CI 0.28 to 0.88; P = 0.02). The bootstrapped 95% CI were similar (graft failure 0.82 to 1.67; graft failure or death 0.67 to 1.23; death 0.28 to 0.94).

DISCUSSION

As in multiple other countries, black patients treated with dialysis in Canada waited longer for a kidney transplant after initiation of dialysis and were less likely to undergo transplantation than white patients, especially for transplants from a living donor; however, black transplant recipients had similar graft survival and lower all-cause mortality compared with white patients, a finding that is strikingly different from that reported in American studies.^{2–5,18,25,26}

Black Americans have lower access to renal transplantation than white Americans, probably because of lower referral rates for transplantation assessment, which may themselves be due to physician attitudes about poor adherence and lower graft success rates among black patients.^17,22,27,28 Numerous studies from the United States also show inferior graft outcomes among black transplant recipients. Data from the United Network for Organ Sharing registry showed that between 1995 and 1999, the 5-yr graft survival rates for deceased donor transplants was 70 and 55%, respectively, for white and black patients. Among living donor transplants, the graft survival rates were 80 and 64%, respectively, for white and black patients. These differences were observed even in HLA-identical sibling transplants, which provided the best results for people of both races but led to markedly superior graft half-lives in white patients (42 versus 27 yr).⁵

In theory, the lack of disparity in graft failure rates between black and white patients in Canada versus the United States might depend on both macro-level factors (health care system and population) and micro-level factors (biologic and other determinants) that affect the transplant recipient. It is possible, although less plausible, that black Americans and the Canadian black population are “biologically” different as a result of historical patterns of immigration. This biologic argument has been used to explain differences in outcomes among black and white Americans for decades, but recent studies have shown that it likely plays a minor role in influencing transplant outcomes.^{11,13,14,19,25,29,30}

A second possible explanation for differences in graft failure in black Americans versus black Canadians is that relative levels of comorbidity may differ between the two populations. For example, a large proportion of black Americans have hypertension listed as their primary renal diagnosis,¹ whereas this was not the case in our study of the Canadian dialysis population during 1990 through 2000. In our analysis, black patients had significantly higher rates of diabetes as a primary renal diagnosis, but white dialysis patients were significantly older than black patients, with a higher prevalence of comorbid diseases including coronary disease, smoking, and peripheral vascular disease. This likely reflects that a higher proportion of white patients undergo transplantation in Canada and are therefore likely to have more comorbidity. Because we did not perform a direct comparison of Canadian and American data, we are unable to compare the level of comorbidity between either white or black patient groups in either of the two countries.

The third (and, in our opinion, the most probable) potential explanation for our findings may relate to differential access to health services. All Canadians who receive government assistance (welfare) are eligible for immunosuppressive medications through provincial drug programs. Recipients who are employed and have private insurance may receive coverage for the majority of their medications through a blend of private and public drug coverage. In contrast, the poor seem to have substantially reduced access to immunosuppressive drugs in the United States. Under the current US system, the cost of immunosuppressive medication is reimbursed in the first 3 to 5 yr after renal transplantation, and much of the graft loss among lower income recipients occurs after reimbursement ends.²⁹ Because black Americans are more likely to be uninsured compared with white Americans, this policy may contribute to their higher risk for graft loss^28,31; however, graft survival was lower in black than white patients even among US veterans, all of whom are eligible for medication coverage through the Veterans Administration medical system,³² and the explanation for this finding remains unclear.

We also found that black transplant recipients had 51% lower mortality after transplantation than white recipients, which is also out of keeping with published US data.³³ The reasons for this are unclear but may again be related to differential access to pre- and posttransplantation care for comorbid disease or differences in the relative burden of comorbidity between the two black populations. Alternatively, because black Canadian patients are less likely than seemingly comparable white patients to receive a kidney transplant, their lower posttransplantation mortality relative to white patients may be due to selection bias. No recent studies have examined characteristics of black versus white Canadian renal transplant patients; however, the lower number of black renal transplant patients in Canada suggests that perhaps there is a disparity in referral or placement on the waiting list for black versus white patients. This may have resulted in only relatively healthier black patients’ receiving a renal transplant. This disparity in the total number of black Canadians’ receiving renal transplantation is concerning and supports previously published studies that showed decreased access to renal transplantation among other minority patient groups in Canada^34,35 and warrants further investigation into possible causes.

Our argument that renal transplant outcomes are influenced by medical systems rather than biology is supported by recently published data from other countries that have medical systems that are similar in structure and funding to Canada's. A recent study from France showed comparable renal transplant outcomes for both white patients and patients of African descent.³⁶ Although less comparable to Canada, Brazil has also been shown to have similar graft survival among black versus white patients in the recipients of living-donor kidneys.³⁷

There are a number of limitations to our study. The use of registry data has inherent shortcomings, including limited availability of clinical variables collected by the Canadian Renal Replacement Registry, the renal database we used for our analysis. Important transplant variables such as HLA typing, cold/warm ischemic time, and donor characteristics would allow for a more in-depth analysis but are not currently available through this national registry. For instance, racial differences in HLA types may have influenced graft survival in white renal transplant recipients, as compared with those who were black. Although we cannot exclude the possibility that cold/warm ischemic time and clinical donor characteristics systematically differed by race, we believe that this is unlikely. Although CORR has a comprehensive collection of prospectively collected data from all Canadian transplant centers, like most registries, it has no formal validation process. The CORR data collection manual indicates that patient racial identity should be coded through self-reported ethnicity, although some (10%) patients had missing data for race. For this to have influenced our results, patients with missing data on race would have had to be systematically different in terms of both race and outcomes compared with those with complete data. We carried out a sensitivity analysis of missing or unknown race data and found no difference between substitution of black or white patients. Similarly, our findings could have been confounded by unmeasured comorbidity or socioeconomic factors. Although we believe that residual confounding is unlikely to have changed our conclusions, the possibilities that missing or incorrect information was partially responsible for our findings should be considered. In addition, we were unable to obtain comorbidities at the time of renal transplantation but had to rely on comorbidity data collected when the patients were on dialysis. Third, we did not have information on the date of placement on the waiting list for transplantation, which would have allowed us to examine whether longer waiting time influenced graft or patient outcomes, and little is known about access to placement on the waiting list for transplantation among Canadian ethnic minorities. This might be especially relevant for black patients, given that patients from ethnic minorities have longer average waiting times in multiple countries such as Australia (Aboriginals) and the United States (black and Native Americans).^38–40 Fourth, we did not have data on the cause of death or graft failure, which would have helped us to speculate as to why our findings differed from those in the United States. Fifth, data regarding donor and immunologic characteristics (e.g., HLA type, cold/warm ischemia time) were not available and would have strengthened our analyses significantly. Sixth, we did not include data on preemptive transplantation; however, this type of transplantation was infrequently performed in Canada during the study period, and thus we believe that this omission is unlikely to have affected our conclusions. Finally, although we studied a large and representative sample from a national database, the number of black patients in our study was relatively small (n = 195). We investigated the stability of our time to graft failure and/or death models using the bootstrap method (with 5000 iterations), which did not change our findings. For example, the 95% CI for the fully adjusted time to death bootstrap model was 0.28 to 0.94 (versus 0.28 to 0.88 from our original model).⁴¹ Although our findings suggest that the risk for graft failure is similar in black and white Canadians, the low number of black patients treated in Canada during the study period means that we cannot exclude a clinically relevant increased risk for graft failure in this population.

Our data suggest that Canada, unlike the United States, has similar renal transplant outcomes for both black and white renal transplant patients. Our results are consistent with the hypothesis that these between-country differences may be due to differences in health care delivery and raises potentially important questions about whether better access to health services for black Americans would improve outcomes after kidney transplantation in this population.

CONCISE METHODS

DISCLOSURES

None.