Redefining the Influence of Ethnicity on Simultaneous Kidney and Pancreas Transplantation Outcomes: A 15-year Single-center Experience.

OBJECTIVE: To examine the largest single-center experience of simultaneous kidney/pancreas transplantation (SPK) transplantation among African-Americans (AAs). BACKGROUND: Current dogma suggests that AAs have worse survival following SPK than white recipients. We hypothesize that this national trend may not be ubiquitous. METHODS: From August 30, 1999, through October 1, 2014, 188 SPK transplants were performed at the University of Alabama at Birmingham (UAB) and 5523 were performed at other US centers. Using Kaplan-Meier survival estimates and Cox proportional hazards regression, we examined the influence of recipient ethnicity on survival. RESULTS: AAs comprised 36.2% of the UAB cohort compared with only 19.1% nationally (P < 0.01); yet, overall, 3-year graft survival was statistically higher among UAB than US cohort (kidney: 91.5% vs 87.9%, P = 0.11; pancreas: 87.4% vs 81.3%; P = 0.04, respectively) and persisted on adjusted analyses [kidney adjusted hazard ratio (aHR): 0.58, 95% confidence interval (95% CI) 0.35-0.97, P = 0.04; pancreas aHR: 0.54, 95% CI 0.34-0.85, P = 0.01]. Among the UAB cohort, graft survival did not differ between AA and white recipients; in contrast, the US cohort experienced significantly lower graft survival rates among AA than white recipients (kidney 5 years: 76.5% vs 82.3%, P < 0.01; pancreas 5 years: 72.2% vs 76.3%, P = 0.01; respectively). CONCLUSION: Among a single-center cohort of SPK transplants overrepresented by AAs, we demonstrated similar outcomes among AA and white recipients and better outcomes than the US experience. These data suggest that current dogma may be incorrect. Identifying best practices for SPK transplantation is imperative to mitigate racial disparities in outcomes observed at the national level.

Cytolytic Induction Therapy Improves Clinical Outcomes in African-American Kidney Transplant Recipients.

OBJECTIVE: Determine the impact of cytolytic versus IL-2 receptor antibody (IL-2RA) induction on acute rejection, graft loss and death in African-American (AA) kidney transplant (KTX) recipients. BACKGROUND: AAs are underrepresented in clinical trials in transplantation; thus, there is controversy regarding the optimal choice of perioperative antibody induction in KTX to improve outcomes. METHODS: National cohort study using US transplant registry data from January 1, 2000 to December 31, 2009 in adult solitary AA KTX recipients, with at least 5 years of follow-up. Multivariable logistic and Cox regression were utilized to assess the outcomes of acute rejection, graft loss, and mortality, with interaction terms to assess effect modification. RESULTS: Twenty-five thousand eighty-four adult AAs receiving solitary KTX were included, 16,927 (67.5%) received cytolytic induction and 8157 (32.5%) received IL-2RA induction. After adjustment for recipient sociodemographics, donor, and transplant characteristics, the use of cytolytic induction therapy reduced the risk of acute rejection by 32% (OR 0.68, 0.62-0.75), graft loss by 9% (HR 0.91, 0.86-0.97), and death by 12% (HR 0.88, 0.83-0.94). There were a number of significant effect modifiers, including public insurance, panel reactive antibody, delayed graft function, and steroid withdrawal; in these groups, cytolytic induction substantially improved clinical outcomes. CONCLUSIONS: These data demonstrate that cytolytic induction therapy, as compared with IL-2RA, reduces the risk of rejection, graft loss, and death in adult AA KTX recipients, particularly in those who are sensitized, receive public insurance, develop delayed graft function, or undergo steroid withdrawal.

Genotype-guided tacrolimus dosing in African-American kidney transplant recipients.

Tacrolimus is dependent on CYP3A5 enzyme for metabolism. Expression of the CYP3A5 enzyme is controlled by several alleles including CYP3A5*1, CYP3A5*3, CYP3A5*6 and CYP3A5*7. African Americans (AAs) have on average higher tacrolimus dose requirements than Caucasians; however, some have requirements similar to Caucasians. Studies in AAs have primarily evaluated the CYP3A5*3 variant; however, there are other common nonfunctional variants in AAs (CYP3A5*6 and CYP3A5*7) that do not occur in Caucasians. These variants are associated with lower dose requirements and may explain why some AAs are metabolically similar to Caucasians. We created a tacrolimus clearance model in 354 AAs using a development and validation cohort. Time after transplant, steroid and antiviral use, age and CYP3A5*1, *3, *6 and *7 alleles were significant toward clearance. This study is the first to develop an AA-specific genotype-guided tacrolimus dosing model to personalize therapy.

Health Disparities in Kidney Transplantation for African Americans.

BACKGROUND: The persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system. SUMMARY: There are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.

Lower kidney allograft survival in African-Americans compared to Hispanic-Americans with lupus.

Background and objective African-Americans and Hispanic-Americans with lupus are the two most common minority groups who receive kidney transplants in the USA. It is unknown if African-Americans and Hispanic-Americans with lupus have similar outcomes after kidney transplantation. In this study, we assessed whether African-Americans compared to Hispanic-Americans have worse kidney allograft survival after risk factors of rejection and other prognostic factors were matched between both groups. Methods Out of 1816 African-Americans and 901 Hispanic-Americans with lupus, who received kidney transplants between 1987 and 2006 and had complete records in the UNOS program, 478 pairs were matched in 16 baseline predictors and follow-up time employing a predicted probability of group membership. The primary outcome was kidney allograft survival. Main secondary outcomes were rejection, allograft failure attributed to rejection, and mortality. Results Matched pairs were predominantly women (81%) with the mean age of 36 years. 96% were on dialysis before transplantation. 89% of recipients received kidneys from deceased donors and 15.5% from expanded criteria donors. 12% of recipients had zero HLA mismatch. African-Americans compared to Hispanic-Americans had lower cumulative allograft survival during 12-year follow-up ( p < 0.001). African-Americans compared to Hispanic-Americans had higher rates of rejection (10.4 vs 6.73 events/100 patients-years; p = 0.0002) and allograft failure attributed to rejection (6.31 vs 3.99; p = 0.0023). However, African-Americans and Hispanic-Americans had similar mortality rates (2.71 vs 2.31; p = 0.4269). Conclusions African-Americans compared to Hispanic-Americans with lupus had lower kidney allograft survival when recognized risk factors of rejection were matched between groups.

Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis.

BACKGROUND: There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. AIMS: To characterize phenotypic variations and liver transplantation outcomes by age group in adults with PSC. METHODS: The United Network for Organ Sharing database was used to identify waitlist registrations for primary liver transplantation in adults with PSC. Patients were split into three age groups: 18-39 (young), 40-59 (middle-aged), and ≥60 (older). Their clinical characteristics and outcomes on the waitlist and post-transplant were compared. RESULTS: Overall, 8272 adults with PSC were listed for liver transplantation during the study period, of which 28.9% were young, 52.0% were middle-aged, and 19.1% were older. The young age group had the greatest male predominance (70.0 vs. 66.2 vs. 65.1%, p = 0.001), the highest proportion of black individuals (20.0 vs. 11.0 vs. 5.5%, p < 0.001), and the most patients listed with concomitant autoimmune hepatitis (2.2 vs. 1.0 vs. 0.8%, p < 0.001). Older patients experienced the greatest waitlist and post-transplant mortality. Graft survival was greatest in the middle-aged group. Young patients were most likely to experience acute rejection (31 vs. 22.8 vs. 18.0%, p < 0.001) and have graft failure due to chronic rejection or PSC recurrence (47.8 vs. 42.3 vs. 17.9%, p < 0.001). CONCLUSIONS: Age-related differences exist among adults with PSC and are associated with outcomes pre- and post-transplant. Young patients may have a more robust immune-related phenotype that is associated with poorer graft survival. Future studies are needed to further investigate these findings.

Impact of the CYP3A5 genotype on the distributions of dose-adjusted trough concentrations and incidence of rejection in Japanese renal transplant recipients receiving different tacrolimus formulations.

BACKGROUND: We investigated the impact of the CYP3A5 genotype on the distributions of dose-adjusted trough concentrations (C 0h/D) and the incidence of rejection in Japanese recipients taking twice-daily (Tac-BID, n = 140) or modified-release once-daily (Tac-QD, n = 80) tacrolimus formulations for 1 year after renal transplantation. METHODS: Logistic regression analysis was carried out to estimate the distinction rate of CYP3A5 genotypes based on the C 0h/D of Tac-BID or Tac-QD. The coefficients of variation (%CVs) were compared in each recipient to estimate the stability of tacrolimus C 0h/D between formulations or CYP3A5 genotypes. RESULTS: Recipients with at least one CYP3A5*1 wild-type allele (EMs) and recipients with homozygous expression of the variant allele CYP3A5*3 (PMs) were significantly identified using the tacrolimus C 0h/D cut-off values of 2.77 and 0.85 ng/mL/mg, respectively, and discrimination rates of 75.3 and 85.4%, respectively, for Tac-BID and Tac-QD groups. The %CV of the tacrolimus C 0h/D in CYP3A5 EMs taking Tac-QD was significantly lower than that in those taking Tac-BID (20.4 versus 23.3%, P = 0.003). The %CV of the tacrolimus C 0h/D was an independent risk factor for rejection (odds ratio = 1.028, P = 0.033). CONCLUSIONS: The tacrolimus C 0h/D values with definite cut-offs for CYP3A5 genotypes were specifically identified in Japanese renal transplant recipients taking Tac-QD. In addition, a larger %CV for the tacrolimus C 0h/D correlated with the incidence of rejection. Consequently, the stability of the C 0h/D achieved using Tac-QD, which was clearly influenced by the CYP3A5 polymorphism, may prevent the development of rejection.

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

Disparities in outcomes for African American (AA) kidney transplant recipients have persisted for 40 years without a comprehensive analysis of evolving trends in the risks associated with this disparity. Here we analyzed U.S. transplant registry data, which included adult Caucasian or AA solitary kidney recipients undergoing transplantation between 1990 and 2009 comprising 202,085 transplantations. During this 20-year period, the estimated rate of 5-year graft loss decreased from 27.6% to 12.8%. Notable trends in baseline characteristics that significantly differed by race over time included the following: increased prevalence of diabetes from 2001 to 2009 in AAs (5-year slope difference: 3.4%), longer time on the waiting list (76.5 more days per 5 years in AAs), fewer living donors in AAs from 2003 to 2009 (5-year slope difference: -3.36%), more circulatory death donors in AAs from 2000-09 (5-year slope difference: 1.78%), and a slower decline in delayed graft function in AAs (5-year slope difference: 0.85%). The absolute risk difference between AAs and Caucasians for 5-year graft loss significantly declined over time (-0.92% decrease per 5 years), whereas the relative risk difference actually significantly increased (3.4% increase per 5 years). These results provide a mixed picture of both promising and concerning trends in disparities for AA kidney transplant recipients. Thus, although the disparity for graft loss has significantly improved, equity is still far off, and other disparities, including living donation rates and delayed graft function rates, have widened during this time.

Genomewide Association Study of Tacrolimus Concentrations in African American Kidney Transplant Recipients Identifies Multiple CYP3A5 Alleles.

We previously reported that tacrolimus (TAC) trough blood concentrations for African American (AA) kidney allograft recipients were lower than those observed in white patients. Subtherapeutic TAC troughs may be associated with acute rejection (AR) and AR-associated allograft failure. This variation in TAC troughs is due, in part, to differences in the frequency of the cytochrome P450 CYP3A5*3 allele (rs776746, expresses nonfunctional enzyme) between white and AA recipients; however, even after accounting for this variant, variability in AA-associated troughs is significant. We conducted a genomewide association study of TAC troughs in AA kidney allograft recipients to search for additional genetic variation. We identified two additional CYP3A5 variants in AA recipients independently associated with TAC troughs: CYP3A5*6 (rs10264272) and CYP3A5*7 (rs41303343). All three variants and clinical factors account for 53.9% of the observed variance in troughs, with 19.8% of the variance coming from demographic and clinical factors including recipient age, glomerular filtration rate, anticytomegalovirus drug use, simultaneous pancreas-kidney transplant and antibody induction. There was no evidence of common genetic variants in AA recipients significantly influencing TAC troughs aside from the CYP3A gene. These results reveal that additional and possibly rare functional variants exist that account for the additional variation.

Role of race in kidney transplant outcomes in children with focal segmental glomerulosclerosis.

It is well established that racial differences exist in kidney transplant outcomes; however, there are no studies which focus on the role of race in transplant outcomes specifically in children diagnosed with FSGS. Associations between race and transplant outcomes in FSGS children were evaluated using the Organ Procurement and Transplantation Network database from 2000 to 2012. Recipients aged 2-21 years who received a kidney-only transplant were included. Multivariate regression models were used to evaluate transplant outcomes by race. Five hundred and thirty-six recipients (59.7% male, 15.6±3.9 years) were black and 1134 (55.7% male, 14.3±5.0 years) were non-black. Graft survival was significantly shorter in the black group (4.2±3.1 vs 4.6±3.3 years, P=.005). Black race was associated with significantly higher risk of graft failure (HR 1.34, 95% CI=1.21-1.49, P<.0001), acute rejection (OR 1.66 95% CI=1.39-1.97, P<.0001), and delayed graft function (OR 1.51, 95% CI=1.33-1.72, P<.001) compared to non-black race. There were no significant differences in mortality, prolonged hospitalization, or FSGS recurrence between groups. Race is a significant predictor for worse transplant outcomes in children with FSGS.

Kidney transplant results in children: progress made, but blacks lag behind.

Early kidney transplant results in children lagged behind corresponding results in adults. Multiple advances over the past three decades have eliminated that gap. Most children now have equal or superior long-term allograft and patient survival compared with adult recipients. However, black children in the United States continue to have allograft survival results inferior to those of non-black children, even after extensive adjustments for socioeconomic status and access to transplantation.

Racial and ethnic disparities in pediatric renal allograft survival in the United States.

This study was undertaken to describe the association of patient race/ethnicity and renal allograft survival among the national cohort of pediatric renal allograft recipients. Additionally, we determined whether racial and ethnic differences in graft survival exist among individuals living in low- or high-poverty neighborhoods and those with private or public insurance. Among 6216 incident, pediatric end-stage renal disease patients in the United States Renal Data System (kidney transplant from 2000 through September, 2011), 14.4% experienced graft failure, with a median follow-up time of 4.5 years. After controlling for multiple covariates, black race, but not Hispanic ethnicity, was significantly associated with a higher rate of graft failure for both deceased and living donor transplant recipients. Disparities were particularly stark by 5 years post transplant, when black living donor transplant recipients experienced only 63.0% graft survival compared with 82.8 and 80.8% for Hispanics and whites, respectively. These disparities persisted among high- and low-poverty neighborhoods and among both privately and publicly insured patients. Notably profound declines in both deceased and living donor graft survival rates for black, compared with white and Hispanic, children preceded the 3-year mark when transplant Medicare eligibility ends. Further research is needed to identify the unique barriers to long-term graft success among black pediatric transplant recipients.

Comparison of longer-term outcomes after kidney transplantation between Hispanic and non-Hispanic whites in the United States.

Little is known about the longer-term kidney transplant outcomes in the rapidly growing Hispanic population. Using the United States Renal Data System, we identified 105 250 Caucasian patients who received a first kidney transplant between January 1, 1996 and December 31, 2010. We tested for differences between Hispanic and non-Hispanic patients in the outcomes of (1) mortality, (2) all-cause graft failure, and (3) graft failure excluding death with a functioning graft. We used Cox regression to estimate (with 95% confidence intervals) multivariable-adjusted cause-specific hazard ratios (aHRCS ) for mortality and all-cause graft failure and subdistribution hazard ratios (aHRSD ) accounting for death as a competing risk for graft failure excluding death with a functioning graft. Both mortality [aHRCS = 0.69 (0.65-0.73)] and all-cause graft failure [aHRCS = 0.79 (0.75-0.83)] were lower in Hispanics. The association between Hispanic ethnicity and graft failure excluding death was modified by age (p < 0.003). Compared with non-Hispanic whites, graft failure excluding death with a functioning graft did not differ in Hispanics aged 18-39 years [aHRSD = 0.96 (0.89-1.05)] or aged 40-59 years [aHRSD = 1.08 (1.00-1.16)], but was 13% lower in those aged ≥60 years [aHRSD = 0.87 (0.78-0.98)]. In conclusion, once accounting for differences in overall survival, better graft survival was found in older Hispanic patients, but among not those aged <60 years.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.

Racial Disparity in Renal Transplantation: Alemtuzumab the Great Equalizer?

OBJECTIVES: Racial disparity as a barrier to successful outcomes in renal transplants for African Americans has been well described. Numerous unsuccessful attempts have been made to identify specific immunologic and socioeconomic factors. The objective of our study was to determine whether alemtuzumab (AL) induction abolishes this discrepancy and improves allograft survival in African American recipients. METHODS: A retrospective chart review of consecutive adult renal transplants was conducted between 2006 and 2014. Kaplan-Meier analysis and hazard ratios were calculated for the African Americans (AA) and white groups. Multiple linear regressions were performed to assess independent variables (race, retransplant, sex, donor type, induction agent) on allograft survival. RESULTS: A significant difference in allograft survival was identified between whites (n = 272) and AA (n = 445), with AA experiencing more graft losses (18.2% vs 12.1%, P = 0.0351). Induction with AL improved outcomes in all transplant recipients. Multiple linear regression identified that the strongest predictor of allograft failure was induction without AL (P < 0.0001). The data for a subset analysis matched for follow-up length demonstrated that whites compared with AA (n = 157, 67 whites and 90 AA) had lower rates of allograft failure in the absence of AL induction (14.9% vs 44.4%, P = 0.0156, hazard ratio = 2.077). In contrast, AL induction (n = 275, 105 whites and 170 AA) eliminated the racial disparity in allograft failure (5.7% vs 9.4%, P = 0.8248, hazard ratio = 1.504). CONCLUSIONS: This is the first study to describe the effects of AL induction therapy on AA renal transplant recipients beyond the first posttransplant year. Our early results suggest that AL induction therapy abolishes the disparity in renal allograft failure.

Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.

OBJECTIVE: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.

Racial and socioeconomic disparities in pediatric and young adult liver transplant outcomes.

Racial and socioeconomic disparities exist in liver transplantation (LT) outcomes among adults, but little research exists for pediatric LT populations. We examined racial differences in graft survival and mortality within a retrospective cohort of pediatric and young adult LT recipients at a large children's transplant center in the Southeast between 1998 and 2011. The association between race/ethnicity and rates of graft failure and mortality was examined with Cox proportional hazards models that were adjusted for demographic and clinical factors as well as individual-level and census tract-level socioeconomic status (SES). Among the 208 LT recipients, 51.0% were white, 34.6% were black, and 14.4% were other race/ethnicity. Graft survival and patient survival were higher for whites versus minorities 1, 3, 5, and 10 years after transplantation. The 10-year graft survival rates were 84% [95% confidence interval (CI) = 76%-91%] for white patients, 60% (95% CI = 46%-74%) for black patients, and 49% (95% CI = 23%-77%) for other race/ethnicity patients. The 10-year patient survival rates were 92% (95% CI = 84%-96%), 65% (95% CI = 52%-79%), and 76% (95% CI = 54%-97%) for the white, black, and other race/ethnicity groups, respectively. In analyses adjusted for demographic, clinical, and socioeconomic characteristics, the rates of graft failure [black: hazard ratio (HR) = 2.59, 95% CI = 1.29-5.45; other: HR = 3.01, 95% CI = 1.23-7.35] and mortality (black: HR = 4.24, 95% CI = 1.54-11.69; other: HR = 3.09, 95% CI = 0.78-12.19) were higher for minority groups versus whites. In conclusion, at a large pediatric transplant center in the Southeastern United States, racial/ethnic disparities exist in pediatric and young adult LT outcomes that are not fully explained by measured SES and clinical factors.

Significant racial differences in the key factors associated with early graft loss in kidney transplant recipients.

BACKGROUND: There is continued and significant debate regarding the salient etiologies associated with graft loss and racial disparities in kidney transplant recipients. METHODS: This was a longitudinal cohort study of all adult kidney transplant recipients, comparing patients with early graft loss (<5 years) to those with graft longevity (surviving graft with at least 5 years of follow-up) across racial cohorts [African-American (AA) and non-AA] to discern risk factors. RESULTS: 524 patients were included, 55% AA, 151 with early graft loss (29%) and 373 with graft longevity (71%). Consistent within both races, early graft loss was significantly associated with disability income [adjusted odds ratio (AOR) 2.2, 95% CI 1.1-4.5], Kidney Donor Risk Index (AOR 3.2, 1.4-7.5), rehospitalization (AOR 2.1, 1.0-4.4) and acute rejection (AOR 4.4, 1.7-11.6). Unique risk factors in AAs included Medicare-only insurance (AOR 8.0, 2.3-28) and BK infection (AOR 5.6, 1.3-25). Unique protective factors in AAs included cardiovascular risk factor control: AAs with a mean systolic blood pressure <150 mm Hg had 80% lower risk of early graft loss (AOR 0.2, 0.1-0.7), while low-density lipoprotein <100 mg/dl (AOR 0.4, 0.2-0.8), triglycerides <150 mg/dl (AOR 0.4, 0.2-1.0) and hemoglobin A1C <7% (AOR 0.2, 0.1-0.6) were also protective against early graft loss in AA, but not in non-AA recipients. CONCLUSIONS: AA recipients have a number of unique risk factors for early graft loss, suggesting that controlling cardiovascular comorbidities may be an important mechanism to reduce racial disparities in kidney transplantation.

The risk of acute rejection and the influence of induction agents in lower-risk African American kidney transplant recipients receiving modern immunosuppression.

BACKGROUND: While kidney transplant recipients of African American (AA) descent are frequently considered at increased risk of acute rejection, the value of induction therapy is not defined in settings of lower immunologic risk and modern immunosuppression. METHODS: Using the Scientific Registry of Transplant Recipients database, we identified 23,244 primary kidney transplant recipients with panel-reactive antibody (PRA) = 0% treated with TAC/MPA and prednisone from 2000 to 2008. We compared acute rejection, graft survival (GS), and patient survival rates among AA and non-AA and further stratified by induction therapy (none, IL2ra, or rATG). RESULTS: One-yr acute rejection was higher in AA than in non-AA overall (14.5% vs. 9.9%, hazard ratio [HR] for acute rejection [AR] 1.43, p < 0.0001) and was higher regardless of induction agent use. Induction therapy was associated with a reduction in AR, but no benefit in GS in AA or non-AA. In AA, rATG (adjusted relative risk [RR] 0.81, CI 0.70-0.94) and IL2ra (adjusted RR 0.80, CI 0.68-0.93) were similarly effective in reducing AR rates, but did not reach comparable outcomes as in non-AA. CONCLUSION: African Americans who are at otherwise lower immunologic risk have a higher risk of rejection despite modern immunosuppression. Depleting or non-depleting induction therapy similarly reduces but does not entirely mitigate this increased risk, with no impact on three-yr GS.