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Issues of race and ethnicity have occupied a prominent role in the evolution of renal transplantation in the United States. (1) Opelz and colleagues first reported in the mid-1970s that patients of dissimilar ethnic backgrounds might face different challenges to successful transplantation (2). As it became increasingly recognized that minorities (primarily African-Americans, but also Native Americans and others) were at disproportionately greater risk of chronic kidney disease (CKD) but disadvantaged in access to organs from deceased donors, the algorithm governing allocation changed accordingly (3,4). Resolution of the other notable ethnic discrepancy among CKD patients (poorer graft survival associated with minority status) remains a challenge. Most commonly, disparate outcomes in majority and minority populations are attributed to some combination of socioeconomic disadvantage and physiologic differences (primarily immunologic in nature).

In this issue of AJT, Pallet and colleagues offer a novel view of the relationship between ethnicity and renal transplantation, emphasizing the global nature of the problem and focusing on outcomes in minority patients (5). While noting the similar geographic origins (sub-Saharan Africa) of black patients transplanted in Paris and African-Americans, these investigators observed no difference in 5-year patient or renal graft survival between African-Europeans and Caucasians. If significant physiologic differences between blacks and whites existed, they should be evident throughout the world, leading Pallet and coworkers to conclude that immunologic or pharmacogenetic factors related to ethnicity are unlikely to account for the poorer outcomes observed in African-Americans.

The most compelling difference in the clinical management of minority patients in France and the United States is the European model of universal, government-sponsored insurance that ensures financial access to not only immunosuppressive medications, but also other agents (antihypertensives, hypoglycemics, etc.) that impact important comorbidities. Indeed, Pallet et al. deduce that lack of coverage must be the major variable placing black Americans at greater risk, a view shared by some on this side of the Atlantic (6). We concur with these investigators, along with participants at a recent US consensus conference, that provision of all medications necessary for optimal posttransplant care should be mandatory and universal (7).

However, we fear the complete explanation of observed ethnic differences in outcomes among US minority populations is not attributable to a single variable, and resolution may prove more difficult than simply providing universal medication coverage. Several prospective studies, in which access to medications was essentially guaranteed, document poorer outcomes among African-Americans, with more rejection and allograft failure despite comparable immunosuppression (8–11). Currently, our best understanding of patient adherence to medical regimens indicates financial resources as playing only a minor role, and a series of studies from Belgium document significant medication non-compliance leading to rejection and allograft failure even under a European system (12,13).

Might there be socioeconomic variables at play other than access to medications? The African-Europeans reported by Pallet and colleagues differ from African-Americans in at least one important aspect: they had the wherewithal to travel from their homes in Africa and the Caribbean to Paris to undergo transplantation, implying greater access to socioeconomic resources than most black Americans. In the United States, black CKD patients are socioeconomically disadvantaged, generally less informed about transplantation and spend substantially longer in the culture of dialysis and chronic illness than their white counterparts (1). While universal health and medication coverage are important, the full impact of these other socioeconomic factors on renal transplant outcomes has not been determined. Even if, as Pallet and coworkers maintain, socioeconomic factors are paramount, it may also be that physiologic differences become more prominent when medical care is inferior and access to medications is difficult. Indeed, some, but not all, data from the United States indicate that when access to medical care is equivalent, differences in outcome are minimized (14,15).

Thus, the question of ethnically-associated physiological differences that may impact immunologic responsiveness lingers over the field. Our superficial understanding and phenotypic characterization of ethnicity and race seem to compromise our scientific ability to fully evaluate, or maybe even define, the issue. Four years ago in this journal, Halloran issued a call for action, decrying the inadequacy of terminology like chronic rejection and chronic allograft nephropathy to define late allograft failure (16). He opined that sufficient scientific tools were now at our disposal to understand the true pathophysiology of graft loss. The result has been initiation of major new efforts to characterize the processes responsible for late allograft injury. Likewise, we no longer should accept poorly informed explanations regarding ethnicity. With the modern tools of genomics, proteomics and pharmacogenetics, we should now be able to either define the underlying basis of physiologic differences (enabling targeted interventions to overcome them) or once and for all disprove that such differences exist. Indeed, while we have generally assumed that any physiologic factors must be primarily immunologic in nature, emerging data in the CKD population are defining ethnic differences in vascular biology that could be of great importance in a transplant setting (17,18). If we persist in the search for clarity with the same vigor and creativity evident in the response of the transplant community to the plight of minorities regarding access to transplantation, answers may soon be forthcoming.

References

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  2. References
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