Immune factors influencing ethnic disparities in kidney transplantation outcomes

Abstract

An influence of ethnicity on the outcomes of kidney transplant recipients has been recognized for several decades. Both immune and nonimmune factors have been explored as potential explanations. Most studies have focused on the inferior outcomes of African-Americans. As a group, African-Americans differ from Caucasians with respect to a number of measurable components of the alloimmune response, including the T-cell repertoire and the expression and function of costimulatory molecules and various cytokines and chemokines. In general, these differences suggest that African-Americans may be high immune responders. However, no single difference in any of these components of alloimmunity satisfactorily explains the disparities in outcomes. It seems probable that some combination of immune factors interacts with nonimmune factors, such as socioeconomic resources, to influence transplant outcomes in a complex manner.

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

“…Studies demonstrate AAs possess differences related to T cell subtypes, immune reactivity to antigens, polymorphisms in HLA and cytokine production that clearly increase immunogenicity. 26 As AAs are considered high immunologic risk, they are likely more susceptible to deleterious outcomes associated with immunosuppression modifications and variability; thus potentially explaining this phenomena of high tacrolimus variability as a mediator of disparate outcomes in AAs. 32, 40–45 …”

“…17–20 There have been numerous studies elucidating the explanatory factors associated with this disparity, including biologic differences (immunologic risk and gene polymorphisms) and socioeconomic disadvantages. 21–26 AAs are substantially more likely to express the CYP 3A5 *1 polymorphism, which is linked to increased tacrolimus clearance and variability. 8, 27–29 We recently conducted an analysis demonstrating that early posttransplant mean 12-hour tacrolimus trough concentrations are significantly lower in AA kidney transplant recipients, as compared to non-AAs, and this was associated with higher rates of acute rejection.…”

Twenty years of evolving trends in racial disparities for adult kidney transplant recipients

“…This decrease in disparities for acute rejection is likely due to the known immunologic risk factors common in AA recipients, including HLA mismatches, higher PRAs, immune hyper-responsiveness and genetic polymorphisms in cytokine production and immunosuppressant metabolism. 37, 38 Steroid utilization at discharge substantially decreased between 2002 and 2005, with a levelling off starting in 2006. Yet, steroids continue to be used more often in AA recipients.…”

Impact of Cardiovascular Risk Factors on Graft Outcome Disparities in Black Kidney Transplant Recipients

“…It is clear that NHBs have unique immunologic characteristics that increase their risk of acute rejection and have socioeconomic disadvantages which create barriers to access to transplant, access to living donors and access to optimal post-transplant care. 12,50 Thus, to date, most of the interventions designed to reduce this disparity have focused on using potent immunosuppression to mitigate immunologic risk and improve access to deceased and living donor transplants. 25 There have been some documented successes in this capacity.…”