Health Disparities in Renal Transplantation

Disparities in access to health care and variations in utilization of services due to race and/or socioeconomic status remain an unfortunate reality in today’s society. The AST’s core purpose reads, "Improving human life by advancing the field of transplantation." This statement is a tagline that the AST has used for over a decade. What is important to notice is that our mission is to improve human life. Our mission is not to improve some human lives while ignoring others. It is therefore essential that the AST provides leadership directed toward resolving these issues, which are often difficult and thorny. 

In December,  AST member Dr. Win Williams published an outstanding body of work that demonstrates how an organ allocation variance related to A2 and B blood types is able to promote equity in organ allocation: First Report on the OPTN National Variance: Allocation of A2/A2B Deceased Donor Kidneys to Blood Group B Increases Minority Transplantation. I have asked him to blog this month on this specific approach to remediating disparities in access to transplantation, and on this subject in general. Next month, as part of a continuing discussion on serving disadvantaged populations, we will be hearing from Ken and Anil about a fantastic conference that the AST hosted on the biology and ethics surrounding APOL1 gene variants and organ donation.

Jim

Winfred W. Williams, M.D.
Associate Chief, Division of Nephrology
Massachusetts General Hospital
Past Chair, OPTN/UNOS Minority Affairs Committee

The term "Health Disparities" in medicine is defined as ethnic and racial differences in the utilization and benefits of the best existing medical practices and therapeutics in a particular field of medicine. For over two decades, such disparities have been identified across many medical and surgical disciplines and was the subject of the seminal Institute of Medicine report, "Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care," (2002). It is well known, too, that health disparities exist in the field of transplantation.

The Organ Procurement Transplant Network (OPTN) is the unified transplant network established by Congress under the National Organ Transplant Act (NOTA) of 1984. The United Network for Organ Sharing (UNOS), under contract of the OPTN, operates the national registry for all organ transplantation and the computerized system for coordinating organ allocation across the U.S.

OPTN/UNOS also sponsor an extensive committee system which is responsible for the development of organ transplant allocation policy. These committees include the Minority Affairs Committee (MAC), Kidney and Pancreas Committees, the Liver Committee, Lung, Histocompatibility, Pediatrics, Patient Affairs, and others. Each of them is comprised of transplant physicians and surgeons, patient advocates, biostatisticians, and professional liaisons from UNOS and the Scientific Registry of Transplant Recipients. Each committee is charged with reviewing scientific data, generally thematically appropriate and title-specific to the committee, which delineate the latest outcomes and trends of interest in transplant medicine. Policy development is critically dependent on in-depth, iterative, and continuous longitudinal data analysis and discussion, and the majority of organ allocation policy development occurs as a shared, multi-committee process.

In 1993, OPTN/UNOS created the MAC to implement and support policy initiatives that might increase minority access to whole organ transplantation primarily focusing (initially) on kidney transplantation. A guiding principle in this work is reflected in the Statement of Principles and Objectives of Equitable Organ Allocation (Graham, 1995). This statement emphasizes the need for a careful balance between the so-called Principle of Utility — the net medical benefit to all transplant patients as a group, and the Principal of Justice — equity and distribution of the benefits and burdens among all transplant patients.

Blood type B is a relatively rare blood type and, therefore, Type B patients wait longer for kidneys and are transplanted at a lesser rate than candidates of any other blood group. Since Type B candidates are most commonly ethnic minorities (approximately 70%), the disparity in transplant rates for recipients with this blood group contributes to the overall lower transplant rates for minority patients. In last month’s Am. J. Transplant., my colleagues and I published the findings of a decade-long study of the first OPTN/UNOS-MAC-sponsored study designed to show that transplantation of blood group A-subtype 2 (or non-A₁) donor kidneys into blood group B recipients could be done successfully (if the natural anti-A titer was less than 1:8), thus increasing the rate of blood group B transplantation.

Two key findings emerged from this study:

1. Graft survival between the A₂ - and A₂B donors-to-B recipients was identical to that of B-to-B pairs.
2. Notably, there was an estimated 10% overall increase in the rate of minority transplantation under this variance without sacrificing graft survival or disadvantaging other groups.

Preliminary results on the MAC variance study, which were reported serially in oral abstracts at ATC and concomitantly with work from the Midwest Transplant Network, laid the foundation for adoption of this variance in the new Kidney Allocation System algorithm (December 2014); it codifies registration of B-recipient candidates for the A2/A2B donor option as an allocation priority.

What’s intriguing about the example above is that it underscores the importance of biological factors and how they may play a role in disparate outcomes between ethnic groups. This is a population biology example of blood group differences between racial groups, which has a rather profound effect on organ allocation.

Another biological example comes from recent data generated from the human genome. The effect here is on outcomes. It is now well known that two genetic variants at the APOL1 locus, G1 and G2, confer an increased risk for non-diabetic CKD in African Americans. These genetic determinants, segregating in the black population, have been shown to have a potent influence on graft outcomes in recipients transplanted from individuals with two APOL1 risk variants. In addition, it is theoretically possible that APOL1 nephropathy variants may influence kidney outcomes after live donation from African Americans, but this question awaits further investigation.

Still, these are important questions applicable to long-term health issues in African American kidney recipients and donors regarding their kidney health as a function of the APOL1 genomic signature. It may be imperative, now, to consider genotyping these and other specific genetic risk variants in at-risk donors and recipients as part of the transplant screening process. A coherent proposal for this genetic risk assessment remains a pressing priority not only for providers but also for the sake of fully informing our patients.