Transplant Disparities

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The development of large databases for end stage renal disease (ESRD) and organ transplantation in the late 1970s and 1980s revealed a number of disturbing trends: 1) blacks in the United States (African Americans) had a disproportionately higher rate of end stage renal disease; 2) access to the kidney transplant wait list and the waiting times for deceased donor kidney transplantation were worse for African Americans; 3) the rates of both living and deceased kidney donation for African Americans were much lower than those for whites; and 4) the results of kidney transplantation (short- and long-term allograft survival and acute rejection rates) were significantly inferior in African Americans compared with non-Hispanic white recipients (15).

The limited access to an optimal therapy and poorer clinical outcomes seen in kidney transplantation were not different from the observations of racial disparities in other areas of medical care in the United States, including coronary artery disease, prostate cancer, lung cancer, orthopedic surgery, hypertension, diabetes mellitus, and preventive gynecological health (6). This pattern warranted attention because the Medicare End Stage Renal Disease program was not only pivotal to kidney transplantation but also represented a celebrated policy enshrining the democratic principles and egalitarian ideals embodied in the constitutional fabric of the United States. That a flagship Medicare program flunked the fundamental premise of equal access for all without regard to socioeconomic status, age, race, or sex has always turned heads and remains newsworthy.

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The seminal publication by Held et al. (7) and the subsequent Institute of Medicine report (8, 9) galvanized the transplant community to address racial disparities in kidney transplantation. To date, much has been accomplished to redress the inequities. HLA-A and HLA-B matching has been eliminated from the point system for allocating deceased donor kidneys. Time since the onset of ESRD has been added to the waiting time. Concerted effort has led to significant increases in deceased donation by African Americans. Pioneering empirical research at a few centers has led to tailored immunosuppressive regimens with better clinical outcomes in African American kidney transplant recipients (10).

Notwithstanding these important achievements, and after more than three decades of half-hearted measures, grandstanding, and hand-wringing, there remain unsettling racial disparities in ESRD therapy. Suboptimal results of kidney transplantation in African American recipients endure in as much magnitude as decades ago. To be sure, suboptimal access and inferior outcomes also exist for Hispanic kidney transplant candidates and recipients, respectively. Unlike other racial issues in the United States, racial disparities in kidney transplantation defy simplification to a “white versus nonwhite” inequity issue—the best allograft survival results and the most optimal access to kidney transplantation are obtained in individuals of Asian extraction.

It is instructive to briefly review where we stand today and what has been done to date. Today, African Americans have a 50 percent lower probability of getting on the kidney transplant wait list compared with whites. This probability has changed very little over time. However, the rate of kidney transplantation once on the wait list has improved because of the changes to the allocation system described above. Even with this improvement, the median wait time remains twice as long in African Americans compared with non-Hispanic whites.

The largest disparity is now evident in kidney transplantation from living donors, in which the rate is two to three times higher in African Americans. The rate of deceased donation in African Americans has improved significantly from 7–8 percent to 13 percent of all deceased donors. The improvement in deceased kidney donation is largely a result of the innovative and tireless efforts of agencies such as the regional organ procurement organizations in Pennsylvania, Texas, Florida, Alabama, and South Carolina, the Association of Organ Procurement Organizations (AOPO), and the Minority Organ Tissue Transplant Education Program (MOTTEP).

Acute rejection rates in the first year after transplant—which used to be 40 to 50 percent in blacks compared with 20 to 30 percent in whites—have been reduced to a much lower rate of 8 to 15 percent in both African Americans and whites. The one-year graft survival rate is now similar in both African Americans and whites at 85 to 90 percent for deceased donor transplants and 95 to 97 percent for living donor kidney transplants, respectively. This is a marked and much welcome contrast to the 1980s and 1990s when the rate of graft loss in the first year was 1.5 to two times as high in African Americans compared to whites.

These improvements in short-term graft survival are largely driven by increased intensity of immunosuppression and posttransplant surveillance. Patient survival has remained comparable between the racial groups over time. Long-term graft survival (five to 10 years) has improved by approximately 10 percent in whites, but African Americans continue to have a long-term graft survival rate that is relatively inferior by 15 to 20 percentage points.

Race-tailored treatments and practices

The kidney transplant literature is inundated with hundreds of articles on racial disparities in kidney transplantation, but progress has been slow and much remains to be done. “Racial” titles on manuscripts are eye-catching, and journal editors may pay homage to race issues by readily accepting manuscripts with such titles whether or not the content is germane or informative on the subject.

Likewise, high-intensity immunosuppressive strategies have been widely adopted in African Americans on the basis of limited empirical and most often weak experimental evidence. Yet there has been an aversion to studying new immunosuppressive drugs in African American recipients so that “high risk” recipients would not dilute the putative findings of registration trials. Transplant professional thought leaders and funding agencies that set research agendas have shown a lack of commitment to study and address racial disparity issues.

Little of what is offered as explanation or basis of action to improve outcomes of kidney transplantation is based on rigorous evidence because seeking such evidence and finding answers takes finances and time—two scarce resources that no one is yet willing to spend. After all, there has not been a single large national scientific gathering with a comprehensive agenda that has been devoted to this problem.

A larger pool of African American transplant professionals is a desirable social objective, but it would not necessarily lead to improved living kidney donation or better care for African American recipients. We remain mired in the prevailing notion that lack of organ donation, noncompliance with immunosuppressive regimens, and physiologic differences in the mean serum concentrations of the 100th cytokine largely account for the problems at hand.

Neither the classic conservative ideology of “blaming the victim” by ascribing limited access to low donation rates (in African Americans) and poorer graft survival to recipient noncompliance, nor the paternalistic liberal position of ascribing all problems to systemic racism, cultural bias, and a “somewhat different” and recalcitrant immunobiology in African Americans offers a promising or productive guide on how best to address these thorny issues.

Role of research and future directions

No adequately powered multicenter prospective study of medical adherence behavior has been conducted in kidney transplantation, let alone convincingly documented that African Americans are less compliant with immunosuppressive regimens, yet this explanation is confidently offered as an important cause of diminished allograft survival in African Americans. It is also a fact that no evidence shows that overt racism or cultural bias play any role in allocation of donor organs to the detriment of African American transplant candidates. Some organized professionals continue to massage the allocation system at great effort to accomplish marginal interracial redistribution of deceased donor organs as a way of redressing racial imbalance.

Given the significance of this issue, it is lamentable that we have yet to conduct an adequately powered multicenter clinical trial to address the question of optimal immunosuppression in African Americans. Not one such study has been sponsored either by the National Institutes of Health (NIH) or the pharmaceutical industry. Instead, posthoc analysis of completed clinical trials and single center retrospective studies have been the main sources of data on how African American kidney transplant recipients should be managed.

The key problem may be that very few individuals and, worse yet, no governmental entity or representative of the pharmaceutical industry is seriously committed to tackling the problems presented by racial disparities in organ transplantation, at least not as can be judged by demonstrable interest in sponsoring or organizing research projects to address the problems. This lack of commitment is not evident from public pronouncements, advertisements, or the medical literature. Symbolic gestures and politically correct attentiveness to racial disparity issues abound ad nauseum.

Given the inadequacy of current approaches, the way forward requires that a number of questions should be tackled with the utmost urgency. What is the most promising package to stimulate an increase in live kidney donation from which African Americans stand to benefit? Should there be a systematic testing through demonstration projects of radical ideas such as significant financial compensation for both deceased and live kidney donation? Which of the immunosuppressive drugs under development confer benefits in African Americans, rather than just giving larger doses to African Americans in phase four clinical trials? What is the optimal posttransplant management scheme that will improve long-term outcomes in African Americans? Should amply reimbursed capitated posttransplant management schemes be tested through private-public partnerships to assess the potential impact of intensive and well-coordinated posttransplant follow-up?

It is time to establish a consortium of committed professionals to conduct research studies and develop guidelines on racial issues in kidney transplantation just as there are consortia for interventional cardiology, AIDS, type 1 diabetes mellitus, breast cancer, and other diseases. The understandable risk aversion of pharmaceutical companies to offer new drugs in development to African American recipients can be addressed by establishing an active collaboration between relevant agencies within NIH, FDA, and the pharmaceutical industry.

One way to start the ball moving toward tangible goals today is for professional societies to assemble the many individuals who have championed these issues to develop a roadmap to advance the agenda of improving access and outcomes of kidney transplantation in African Americans and other minorities. Unless a new course is charted and vigorously traveled, the next generation will lament the same appalling statistics and revisit an even greater magnitude of unnecessary human suffering, ill health, and premature deaths of untold number of those with end stage kidney disease.

References

1. 

Opelz G, Mickey MR, Terasaki PI: Influence of race on kidney transplant survival. Transpl Proceedings 1977; 9:137–42.

2. 

Relman AS. Race and end-stage renal disease [editorial]. New Engl J Med 1982; 306:1290–1.

3. 

Shapiro R, McCauley J, Scantlebury V, et al: Effect of recipient race on waiting time for renal transplantation at the University of Pittsburgh. Transpl Proceedings 1993; 25:2458–9.

4. 

McDonald JC: Issues related to race in transplantation. Transpl Proceedings 1989; 21:3411–2; discussion 3–8.

5. 

Koyama H, Cecka JM: Race effects. Clin Transplants 1991; 269–80.

6. 

Geiger HJ: Race and health care—an American dilemma? N Engl J Med 1996; 335:815–16.

7. 

Held PJ, Pauly MV, Bovbjerg RR, Newmann J, Salvatierra O, Jr.: Access to kidney transplantation. Has the United States eliminated income and racial differences? Arch Intern Med 1988; 148:2594–600.

8. 

Levinsky NG, Rettig RA: The Medicare end-stage renal disease program. A report from the Institute of Medicine. N Engl J Med 1991; 324:1143–8.

9. 

Rettig AR, Levinsky GN: Kidney failure and the federal government. Committee for the Study of the Medicare ESRD Program, Division of Health Care Services, Institute of Medicine: National Academy of Sciences; 1991.

10. 

Gaber AO, First MR, Tesi RJ, et al.: Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transpl 1998; 66:29–37.