A lack of living donor renal transplantation for Asian children represents an opportunity to improve pediatric healthcare.

INTRODUCTION: The relationship between pediatric primary care practitioners and families provides an early opportunity to address ethnic/racial pediatric subspecialty health care disparities. Living donor pediatric renal transplantation is safe and more effective than deceased donor renal transplantation. The purpose of this study is to identify groups of children who may be less likely to receive living donor renal transplantation, as the first step in assisting pediatric clinicians to increase living donor renal transplantation. METHOD: We employed a retrospective cohort design. We analyzed data from the medical records of 80 children receiving renal transplantation over 20 years in a large pediatric medical center. RESULTS: The proportions of children receiving a living donor renal allograft differed by ethnicity/race (P = .04). Specifically, children of Asian ethnicity/ race were significantly less likely than children of White ethnicity/race to receive a living donor renal allograft (P = .01). There were no significant differences in age at transplantation or wait time for deceased donor transplantation. DISCUSSION: We discuss the possible reasons for the discrepancy and potential directions for family-centered pediatric practice, policy, and research to address this potential pediatric healthcare disparity.

Practice patterns and outcomes in retransplantation among pediatric kidney transplant recipients.

BACKGROUND: More than 25% of pediatric kidney transplants are lost within 7 years, necessitating dialysis or retransplantation. Retransplantation practices and the outcomes of repeat transplantations, particularly among those with early graft loss, are not clear. METHODS: We examined retransplantation practice patterns and outcomes in 14,799 pediatric (ages <18 years) patients between 1987 and 2010. Death-censored graft survival was analyzed using extended Cox models and retransplantation using competing risks regression. RESULTS: After the first graft failure, 50.4% underwent retransplantation and 12.1% died within 5 years; after the second graft failure, 36.1% underwent retransplantation and 15.4% died within 5 years. Prior preemptive transplantation and graft loss after 5 years were associated with increased rates of retransplantation. Graft loss before 5 years, older age, non-Caucasian race, public insurance, and increased panel-reactive antibody were associated with decreased rates of retransplantation. First transplants had lower risk of graft loss compared with second (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.64-0.80; P<0.001), third (aHR, 0.62; 95% CI, 0.49-0.78; P<0.001), and fourth (aHR, 0.44; 95% CI, 0.24-0.78; P=0.005) transplants. However, among patients receiving two or more transplants (conditioned on having lost a first transplant), second graft median survival was 8.5 years despite a median survival of 4.5 years for the first transplant. Among patients receiving three or more transplants, third graft median survival was 7.7 years despite median survivals of 2.1 and 3.1 years for the first and second transplants. CONCLUSIONS: Among pediatric kidney transplant recipients who experience graft loss, racial and socioeconomic disparities exist with regard to retransplantation, and excellent graft survival can be achieved with retransplantation despite poor survival of previous grafts.

Young aboriginals are less likely to receive a renal transplant: a Canadian national study.

BACKGROUND: Previous studies have demonstrated Aboriginals are less likely to receive a renal transplant in comparison to Caucasians however whether this applies to the entire population or specific subsets remains unclear. We examined the effect of age on renal transplantation in Aboriginals. METHODS: Data on 30,688 dialysis (Aboriginal 2,361, Caucasian 28, 327) patients obtained between Jan. 2000 and Dec. 2009 were included in the final analysis. Racial status was self-reported. Cox proportional hazards, the Fine and Grey sub-distribution method and Poisson regression were used to determine the association between race, age and transplantation. RESULTS: In comparison to Caucasians, Aboriginals were less likely to receive a renal transplant (Adjusted HR 0.66 95% CI 0.57-0.77, P < 0.0001) however after stratification by age and treating death as a competing outcome, the effect was more predominant in younger Aboriginals (Age 18-40: 20.6% aboriginals vs. 48.3% Caucasians transplanted; aHR 0.50(0.39-0.61), p < 0.0001, Age 41-50: 10.2% aboriginals vs. 33.9% Caucasians transplanted; aHR 0.46(0.32-0.64), p = 0.005, Age 51-60: 8.2% aboriginals vs. 19.5% Caucasians transplanted; aHR0.65(0.49-0.88), p = 0.01, Age >60: 2.7% aboriginals vs. 2.6% Caucasians transplanted; aHR 1.21(0.76-1.91), P = 0.4, Age X race interaction p < 0.0001). Both living and deceased donor transplants were lower in Aboriginals under the age of 60 compared to Caucasians. CONCLUSION: Younger Aboriginals are less likely to receive a renal transplant compared to their Caucasian counterparts, even after adjustment for comorbidity. Determination of the reasons behind these discrepancies and interventions specifically targeting the Aboriginal population are warranted.

Disparities among Blacks, Hispanics, and Whites in time from starting dialysis to kidney transplant waitlisting.

BACKGROUND: Although a longer time on dialysis before kidney transplant waitlisting has been shown for Blacks versus non-Blacks, relatively few studies have compared this outcome between Hispanics and Whites. METHODS: A multivariable analysis of 1910 (684 Black, 452 Hispanic, and 774 White) consecutive patients waitlisted at our center for a primary kidney transplant between 2005 and mid-2010 was performed for time from starting dialysis to waitlisting (months), the percentage who were preemptively waitlisted (waitlisted before starting dialysis), and time from starting dialysis to waitlisting after excluding the preemptively waitlisted patients. RESULTS: The variables associated with significantly longer median times from starting dialysis to waitlisting and less preemptive waitlisting included Medicare insurance for patients ages <65 years (by far, the most significant variable in each analysis), Black race, higher percentage of households in the patient's zip code living in poverty, being a non-U.S. citizen (for preemptive waitlisting), Medicaid insurance, waitlisted for kidney-alone (vs. kidney-pancreas) transplant, and higher body mass index (longer median times for the latter three variables). Although the effect of Black race was mostly explained by significant associations with lower socioeconomic status (Medicare insurance for patients ages <65 years and greater poverty in the patient's zip code), an unexplained component still remained. The univariable differences showing poorer outcomes for Hispanics versus Whites were smaller and completely explained in multivariable analysis by significant associations with lower socioeconomic status and non-U.S. citizenship. CONCLUSION: Black and Hispanic patients had significantly longer times from starting dialysis to waitlisting, in large part related to their lower socioeconomic status and less preemptive waitlisting. A greater focus on earlier nephrology care may help to erase much of these disparities.

Kidney graft survival in Europe and the United States: strikingly different long-term outcomes.

BACKGROUND: Kidney graft survival has never been systematically compared between Europe and the United States. METHODS: Applying period analysis to first deceased-donor (DD) and living-donor kidney grafts from the United Network for Organ Sharing/Organ Procurement and Transplantation Network for the United States and the Collaborative Transplant Study for Europe, we compared overall and age-specific 1-, 5-, and 10-year graft survival for Europeans and white, African, and Hispanic Americans for the 2005 to 2008 period. A Cox regression model was used to adjust for differences in patient characteristics. RESULTS: For the 2005 to 2008 period, 1-year survival for DD grafts was equal (91%) between Europeans and white and Hispanic Americans, whereas it was slightly lower for African Americans (89%). In contrast, overall 5- and 10-year graft survival rates were considerably higher for Europe (77 and 56%, respectively) than for any of the three U.S. populations (whites, 71 and 46%, Hispanic, 73 and 48%, and African American, 62 and 34%). Differences were largest for recipient ages 0 to 17 and 18 to 29 and generally increased beyond 3 to 4 years after transplantation. Survival patterns for living-donor grafts were similar as those seen for DD grafts. Adjusted hazard ratios for graft failure in United Network for Organ Sharing white Americans ranged between 1.5 and 2.3 (all P<0.001) for 2 to 5 years after transplantation, indicating that lower graft survival is not explained by differences in baseline patient characteristics. CONCLUSIONS: Long-term kidney graft survival rates are markedly lower in the United States compared with Europe. Identifying actionable factors explaining long-term graft survival differences between Europe and the United States is a high priority for improving long-term graft survival.

Review of ethnic disparities in access to renal transplantation.

Renal transplantation is the gold standard treatment for patients with end-stage renal disease and is associated with several advantages over dialysis, including increased quality of life, reduced morbidity and mortality, and lower healthcare costs. Barring the constraints of a limited organ supply, the goals of the patient care should focus on attaining renal transplantation while minimizing, or even eliminating, time spent on dialysis. Disparities in access to renal transplantation between African Americans and Caucasians have been extensively documented, with African Americans having significantly poorer access. There is a growing corpus of literature examining the determinants of reduced access among other racial ethnic minority groups, including Hispanics. These determinants include patient and physician preference, socioeconomic status, insurance type, patient education, and immunologic factors. We review these determinants in access to renal transplantation in the United States among all races and ethnicities.

Association of race and insurance type with delayed assessment for kidney transplantation among patients initiating dialysis in the United States.

BACKGROUND AND OBJECTIVES: The extent to which racial and socioeconomic disparities in access to kidney transplantation are related to not being assessed for transplant suitability before or shortly after the time of initiation of dialysis is not known. The aims of this study were to determine whether there were disparities based on race, ethnicity, or type of insurance in delayed assessment for transplantation and whether delayed assessment was associated with lower likelihood of waitlisting and kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used data from the US Renal Data System and included 426,489 adult patients beginning dialysis in the United States between January 1, 2005 and September 30, 2009 without prior kidney transplant. RESULTS: Overall, 12.5% of patients had reportedly not been assessed for transplantation. Patients without private insurance were more likely to be reported as not assessed (multivariable adjusted odds ratio=1.33, 95% confidence interval=1.28-1.40 for Medicaid), with a pronounced racial disparity but no ethnic disparity among patients aged 18 to <35 years (odds ratio=1.27, 95% confidence interval=1.13-1.43; P<0.001 for interaction with age). Not being assessed for transplant around the time of dialysis initiation was associated with lower likelihood of waitlisting in multivariable analysis (hazard ratio=0.59, 95% confidence interval=0.57-0.62 in the first year) and transplantation (hazard ratio=0.46, 95% confidence interval=0.41-0.51 in the first year), especially within the first 2 years. CONCLUSIONS: Racial and insurance-related disparities in transplant assessment potentially delay transplantation, particularly among younger patients.

Racial disparities in access to pediatric kidney transplantation since share 35.

Share 35 was enacted in 2005 to shorten transplant wait times and provide high-quality donors to children with ESRD. To investigate the possible effect of this policy on racial disparities in access to pediatric transplantation, we analyzed data from the US Renal Data System before and after Share 35. Among 4766 pediatric patients with incident ESRD, the probability of receiving a deceased-donor kidney transplant increased 46% after Share 35, with Hispanics experiencing the greatest improvements (increases of 81% for Hispanics, 45% for blacks, and 37% for whites). On average, patients received a deceased-donor kidney transplant earlier after Share 35, but this finding varied by race: 63 days earlier for whites, 90 days earlier for blacks, and 201 days earlier for Hispanics. Furthermore, a shift from living- to deceased-donor sources occurred with Share 35 for all races, with a 25% reduction in living donors for whites compared with 48% and 46% reductions for Hispanics and blacks, respectively. In summary, Share 35 seems to have attenuated racial disparities in the time to and probability of children receiving a deceased-donor kidney transplant. These changes coincided with changes in the rates of living-donor sources, which vary by race. Future studies should explore how these changes may impact racial differences in long-term graft outcomes.

The "House Calls" trial: a randomized controlled trial to reduce racial disparities in live donor kidney transplantation: rationale and design.

Despite a substantially lower rate of live donor kidney transplantation among Black Americans compared to White Americans, there are few systematic efforts to reduce this racial disparity. This paper describes the rationale and design of a randomized controlled trial evaluating the comparative effectiveness of three different educational interventions for increasing live donor kidney transplantation in Black Americans. This trial is a single-site, urn-randomized controlled trial with a planned enrollment of 180 Black Americans awaiting kidney transplantation. Patients are randomized to receive transplant education in one of three education conditions: through group education at their homes (e.g., House Calls), or through group (Group-Based) or individual education (Individual Counseling) in the transplant center. The primary outcome of the trial is the occurrence of a live donor kidney transplant, with secondary outcomes including living donor inquiries and evaluations as well as changes in patient live donor kidney transplantation readiness, willingness, knowledge, and concerns. Sex, age, dialysis status, and quality of life are evaluated as moderating factors. Findings from this clinical trial have the potential to inform strategies for reducing racial disparities in live donor kidney transplantation. Similar trials have been developed recently to broaden the evaluation of House Calls as an innovative disparity-reducing intervention in kidney transplantation.

Impact of race on predialysis discussions and kidney transplant preemptive wait-listing.

BACKGROUND/AIMS: US registry data have consistently shown that blacks are less likely than whites to be wait-listed before beginning dialysis. METHODS: The Comprehensive Dialysis Study (CDS) was a special study conducted by the US Renal Data System (USRDS) in which a national cohort of patients who began maintenance dialysis therapy in 2005-2007 were asked whether kidney transplantation (KT) had been discussed with them before they started dialysis. Using responses from black and white CDS participants and information from the USRDS, we investigated preemptive wait-listing as a function of patient-reported predialysis KT discussion. RESULTS: Among those reporting early KT discussion, 31.0% of patients preemptively wait-listed were black, compared to 27.5% of those not preemptively wait-listed. Two thirds of preemptively wait-listed patients had received nephrology care more than 12 months before starting dialysis and reported that KT was discussed with them 12 months or more before dialysis. Early KT discussion and higher serum albumin and hemoglobin levels remained significant predictors of preemptive wait-listing in an adjusted logistic regression analysis. Among those preemptively wait-listed, 33% of blacks and 60% of whites had received a transplant by September 30, 2009 (study end date). CONCLUSION: Early KT discussion appeared to reduce barriers to black patients' waiting list placement before the start of dialysis, which in turn may facilitate earlier access to a deceased donor organ transplant.

Renal health and transplantation: a focus on ethnicity.

It is widely acknowledged within the United Kingdom that there are significant inequalities in renal health and transplant services--in relation to demand for, access to and waiting times for these services--between minority ethnic groups in particular. This phenomenon is not unique to the United Kingdom and affects many other countries that have a strong tradition of immigration. The solutions to reducing these inequalities are multi-faceted and require both short-term and long-term policy and resource-driven initiatives. In the short term, there is an urgent need to increase the number of organ donors from minority ethnic groups which will positively impact upon improved access to transplantation and contribute to reduced waiting times. The increase in donor registration can only be achieved if there are evidence-based, concerted and adequately resourced efforts to engage with minority ethnic communities at grass-roots level. In the long term, public health interventions are required that proactively seek to prevent and manage long-term conditions among the United Kingdom's multi-ethnic and multi-faith population, thereby reducing the demand for transplantation.

[Evolution of the access to the kidney transplantation in France of foreign patients and French patients living in overseas territories]. / Évolution de l'accès à la greffe rénale en France des patients étrangers ou résidant outre-mer.

In France, foreign patients, whether resident or not in France, can register on the national waiting list under administrative and financial conditions. We performed a retrospective analysis to evaluate the access to kidney transplantation on a cohort 2004-2008, using the national registry. Among the 14,732 patients registered during this period, 15.3% are of non-French nationality (3.4% other European, 5.9% North African, 3.9% sub-Saharan African, 2.9% other). Among the 84.6% of French nationality, 3.3% are living in French overseas territories. Compared to the 17.6-month median waiting time of the cohort, median waiting time differs significantly between groups, from 15.7 months for mainland French patients to 36 months for sub-Saharan African patients. Despite the regular development of the allocation rules, these disparities in access to transplantation are mainly, but not completely, explained by blood group or HLA matching difficulties. After adjustment for the other factors known to be significantly linked to a difficult access to transplantation, North and sub-Saharan African patients have the worst difficulties. Future research should consider nonmedical factors, such as socio-economic or socio-cultural factors, potentially relevant to avoid disparities in access to transplantation and should aim at developing specific interventions.

Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients.

BACKGROUND: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. METHODS: We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation. RESULTS: Patients with the CYP3A5*3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of ≥1 CYP3A5*3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5*1 alleles, might be associated with higher tacrolimus dose per kilogram. CONCLUSIONS: The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients.

Racial disparities in pediatric access to kidney transplantation: does socioeconomic status play a role?

Racial disparities persist in access to renal transplantation in the United States, but the degree to which patient and neighborhood socioeconomic status (SES) impacts racial disparities in deceased donor renal transplantation access has not been examined in the pediatric and adolescent end-stage renal disease (ESRD) population. We examined the interplay of race and SES in a population-based cohort of all incident pediatric ESRD patients <21 years from the United States Renal Data System from 2000 to 2008, followed through September 2009. Of 8452 patients included, 30.8% were black, 27.6% white-Hispanic, 44.3% female and 28.0% lived in poor neighborhoods. A total of 63.4% of the study population was placed on the waiting list and 32.5% received a deceased donor transplant. Racial disparities persisted in transplant even after adjustment for SES, where minorities were less likely to receive a transplant compared to whites, and this disparity was more pronounced among patients 18-20 years. Disparities in access to the waiting list were mitigated in Hispanic patients with private health insurance. Our study suggests that racial disparities in transplant access worsen as pediatric patients transition into young adulthood, and that SES does not explain all of the racial differences in access to kidney transplantation.

The role of race and poverty on steps to kidney transplantation in the Southeastern United States.

Racial disparities in access to renal transplantation exist, but the effects of race and socioeconomic status (SES) on early steps of renal transplantation have not been well explored. Adult patients referred for renal transplant evaluation at a single transplant center in the Southeastern United States from 2005 to 2007, followed through May 2010, were examined. Demographic and clinical data were obtained from patient's medical records and then linked with United States Renal Data System and American Community Survey Census data. Cox models examined the effect of race on referral, evaluation, waitlisting and organ receipt. Of 2291 patients, 64.9% were black, the mean age was 49.4 years and 33.6% lived in poor neighborhoods. Racial disparities were observed in access to referral, transplant evaluation, waitlisting and organ receipt. SES explained almost one-third of the lower rate of transplant among black versus white patients, but even after adjustment for demographic, clinical and SES factors, blacks had a 59% lower rate of transplant than whites (hazard ratio = 0.41; 95% confidence interval: 0.28-0.58). Results suggest that improving access to healthcare may reduce some, but not all, of the racial disparities in access to kidney transplantation.

Anthropology, organ transplantation and the immune system: resituating commodity and gift exchange.

This article reflects on contributions from medical anthropology to our understanding of the bio-social and bio-political implications of renal transplantation. Taking up the idea of transplantation as a 'complex', a vast assemblage of people, places, practices and procedures which intersect medical, social and cultural domains, I point to a reliance in the anthropological literature on overly pre-determined conceptual frameworks, organised around a distinct polarisation between organ giving and receiving, where one side (supply) takes analytical, and indeed moral, precedence over the other (receipt). These frameworks tend to fail us when it comes to thinking about the wider social, cultural and political implications of transplant technologies. In an attempt to offer a less polarised view, I draw attention to the material and symbolic role of the immune system in transplantation and the ways in which it simultaneously shapes opportunities for procurement and the lived realities of recipiency. This helps us see the many complex ways in which suffering and inequality are constituted all along the variegated chains of supply and demand that are internal to, and made possible by, transplantation practices themselves.

Immune factors influencing ethnic disparities in kidney transplantation outcomes.

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.

Low bone mineral density and nutritional vitamin D deficiency in pediatric renal transplant recipients: Assessment of risk factors and response to oral vitamin D therapy.

VitD deficiency and bone disease are common after Tx. Prevalence and risk factors for low VitD and BMD and response to VitD therapy were investigated in pediatric renal Tx recipients. 25-hydroxy VitD levels of 71 Tx were compared to 54 healthy AA children. DXA of 44 Tx were compared to 47 AA controls. Of Tx, 59% were AA. Majority (59.1%) of Tx were VitD deficient (23.9%) or insufficient (35.2%). Prevalence of low VitD levels was double in AA (73.9%) vs. non-AA Tx (37.7%), (p = 0.003). Low VitD among Tx was associated with AA ethnicity (p < 0.01), winter (p < 0.05), older age (p < 0.05), males (p < 0.05) and time <6 months post Tx (p < 0.05). Tx with low VitD were treated with oral ergocalciferol or cholecalciferol (23 each); 13% treated with ergocalciferol vs. 82.6% treated with cholecalciferol achieved repletion (p < 0.0001). Of 36 Tx with whole body DXA, 19.5% had BMD (z < -1) after height adjustment. AA Tx had 3.4-fold higher risk of low BMD vs. controls (p < 0.05). Low VitD and BMD are prevalent in children after renal Tx. Better repletion of VitD is achieved with cholecalciferol.