Kidney transplantation access and outcomes for Aboriginal and Torres Strait Islander children and young adults, 1963-2020: an ANZDATA registry study.

OBJECTIVES: To assess differences between Aboriginal and Torres Strait Islander and non-Indigenous Australian children and young adults in access to and outcomes of kidney transplantation. STUDY DESIGN: A cohort study based on prospectively collected data; analysis of Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. SETTING, PARTICIPANTS: Children and young adults aged 0-24 years who commenced kidney replacement therapy in Australia during 1963-2020. MAIN OUTCOME MEASURES: Proportions of children and young adults who received kidney transplants within five years of commencing dialysis; 5- and 10-year death-censored graft survival; and 5- and 10-year survival of children and young adults who received kidney transplants or who remained on dialysis. RESULTS: During 1963-2020, 3736 children and young adults received kidney replacement therapy in Australia: 213 (5.8%) Aboriginal and Torres Strait Islander and 3523 (94.2%) non-Indigenous children and young adults. During follow-up (median, eight years; interquartile range [IQR], 2.6-15 years), 2762 children and young adults received kidney transplants: 93 Aboriginal and Torres Strait Islander (43.7% of those receiving kidney replacement therapy) and 2669 non-Indigenous children and young adults (75.8%). Smaller proportions of Aboriginal and Torres Strait Islander than of non-Indigenous children and young adults received transplants within five years of commencing dialysis (99, 46% v 2924, 83.0%), received living donor transplants (19, 20% v 1170, 43.9%), or underwent pre-emptive transplantation (one, 1.1% v 363, 13.6%). Five-year graft survival for Aboriginal and Torres Strait Islander recipients was similar to non-Indigenous recipients (61% v 75%; adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 0.02-2.05), but 10-year graft survival was lower (35% v 61%; aHR, 1.69; 95% CI, 1.25-2.28). Five- and 10-year survival after kidney transplantation was similar for Aboriginal and Torres Strait Islander and non-Indigenous people. Among those who remained on dialysis, 10-year survival was poorer for Aboriginal and Torres Strait Islander than non-Indigenous children and young adults (aHR, 1.50; 95% CI, 1.08-2.10). CONCLUSIONS: Five-year graft and recipient survival were excellent for Aboriginal and Torres Strait Islander children and young adults who received kidney transplants; however, a lower proportion received transplants within five years of dialysis initiation, than non-Indigenous children and young adults. Improving transplant access within five years of dialysis commencement should be a priority.

The survival benefit of deceased donor kidney transplantation for Aboriginal and Torres Strait Islander people, 2006-20: a retrospective national cohort study.

OBJECTIVES: To quantify the survival benefit of kidney transplantation for Aboriginal and Torres Strait Islander people waitlisted for deceased donor kidney transplantation in Australia. STUDY DESIGN: Retrospective cohort study; analysis of linked data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry, the Australia and New Zealand Organ Donation (ANZOD) registry, and OrganMatch (Australian Red Cross). SETTING, PARTICIPANTS: All adult Aboriginal and Torres Strait Islander people (18 years or older) who commenced dialysis in Australia during 1 July 2006 - 31 December 2020 and were included in the kidney-only deceased donor transplant waiting list. MAIN OUTCOME MEASURES: Survival benefit of deceased donor kidney transplantation relative to remaining on dialysis. RESULTS: Of the 4082 Aboriginal and Torres Strait Islander people who commenced dialysis, 450 were waitlisted for kidney transplants (11%), of whom 323 received deceased donor transplants. Transplantation was associated with a significant survival benefit compared with remaining on dialysis after the first 12 months (adjusted hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.73). This benefit was similar to that for waitlisted non-Indigenous people who received deceased donor kidney transplants (adjusted HR, 0.47; 95% CI, 0.40-0.57; Indigenous status interaction: P = 0.22). CONCLUSIONS: From twelve months post-transplantation, deceased donor transplantation provides a survival benefit for Aboriginal and Torres Strait Islander people. Our findings provide evidence that supports efforts to promote the waitlisting of Aboriginal and Torres Strait Islander people who are otherwise eligible for transplantation.

Association of race and ethnicity with initial surgical hemodialysis access type in a safety net system.

OBJECTIVES: Prior studies have found lower arteriovenous fistula (AVF) creation rates in Black and Hispanic patients. Whether this is due to health care disparities or other differences is unclear. Our objective was to evaluate the racial/ethnic differences in initial surgical access type within a high-volume, safety net system with predominantly Black and Hispanic populations. METHODS: A retrospective review of initial hemodialysis (HD) access in consecutive cases between 2014 and 2019 was conducted from all five safety net hospitals in a health care system that primarily treats underserved patients. Patient data collected included race, ethnicity, sex, comorbidities, and initial arteriovenous (AV) access type (AV fistula [AVF] vs AV graft [AVG]). The rates of cephalic vein-based AVF (CAVF; radiocephalic, brachiocephalic) were compared with basilic and brachial vein AVF (BAVF), because the latter are performed as two stages. Bivariate and multivariate logistic regression models were adjusted for demographic and clinical variables to evaluate the relationship between race/ethnicity, surgical access type, and comorbid conditions. RESULTS: We included 1334 patients (74% Hispanic, 9% Black, 7% Asian, 2% White, 8% other) who underwent first-time surgical HD access creation. The majority were male (818 [63%]). Medical comorbidities were equal among groups, except for chronic obstructive pulmonary disease and stroke, which were higher in Black patients (P < .005 and P = .005, respectively). Overall, 1303 patients (98%) underwent AVF creation and 31 AVG creation (2%), with no difference between race/ethnicity in AVF vs AVG creation. Of the AVF cohort, 991 (76%) had a CAVF and 312 (24%) had a BAVF. Males were more likely than females to get a CAVF (65% vs 35%; P = .002). CONCLUSIONS: Within our safety net health system, where most patients are under-represented minorities, nearly all patients undergoing HD access had an AVF as their initial surgery with no difference in race/ethnicity. AVF type received differed by race, with Black patients twice as likely to undergo BAVF, which required two stages. Further studies are needed to identify the reasons for these differences.

Social Risk and Dialysis Facility Performance in the First Year of the ESRD Treatment Choices Model.

Importance: The End-Stage Renal Disease Treatment Choices (ETC) model randomly selected 30% of US dialysis facilities to receive financial incentives based on their use of home dialysis, kidney transplant waitlisting, or transplant receipt. Facilities that disproportionately serve populations with high social risk have a lower use of home dialysis and kidney transplant raising concerns that these sites may fare poorly in the payment model. Objective: To examine first-year ETC model performance scores and financial penalties across dialysis facilities, stratified by their incident patients' social risk. Design, Setting, and Participants: A cross-sectional study of 2191 US dialysis facilities that participated in the ETC model from January 1 through December 31, 2021. Exposure: Composition of incident patient population, characterized by the proportion of patients who were non-Hispanic Black, Hispanic, living in a highly disadvantaged neighborhood, uninsured, or covered by Medicaid at dialysis initiation. A facility-level composite social risk score assessed whether each facility was in the highest quintile of having 0, 1, or at least 2 of these characteristics. Main Outcomes and Measures: Use of home dialysis, waitlisting, or transplant; model performance score; and financial penalization. Results: Using data from 125 984 incident patients (median age, 65 years [IQR, 54-74]; 41.8% female; 28.6% Black; 11.7% Hispanic), 1071 dialysis facilities (48.9%) had no social risk features, and 491 (22.4%) had 2 or more. In the first year of the ETC model, compared with those with no social risk features, dialysis facilities with 2 or more had lower mean performance scores (3.4 vs 3.6, P = .002) and lower use of home dialysis (14.1% vs 16.0%, P < .001). These facilities had higher receipt of financial penalties (18.5% vs 11.5%, P < .001), more frequently had the highest payment cut of 5% (2.4% vs 0.7%; P = .003), and were less likely to achieve the highest bonus of 4% (0% vs 2.7%; P < .001). Compared with all other facilities, those in the highest quintile of treating uninsured patients or those covered by Medicaid experienced more financial penalties (17.4% vs 12.9%, P = .01) as did those in the highest quintile in the proportion of patients who were Black (18.5% vs 12.6%, P = .001). Conclusions: In the first year of the Centers for Medicare & Medicaid Services' ETC model, dialysis facilities serving higher proportions of patients with social risk features had lower performance scores and experienced markedly higher receipt of financial penalties.

Navigating Living Kidney Donation and Transplantation Among South Asian Canadians: The ACTION Project.

RATIONALE & OBJECTIVE: South Asian (SA) Canadians with kidney failure have a 50%-77% lower likelihood of kidney transplant and are less likely to identify potential living donors (LDs). This study aimed to identify health system-, patient-, and community-level barriers and facilitators for accessing LD kidney transplantation in the SA community to inform the development of health system- and community-level interventions to address barriers. STUDY DESIGN: Qualitative study. SETTING & PARTICIPANTS: 20 SA recipients of an LD or deceased-donor kidney transplant, 10 SA LDs, and 41 general SA community members. ANALYTICAL APPROACH: In-depth multilingual interviews were conducted with recipients and LDs. Gender-, language-, and age-stratified focus groups were conducted with general SA community members. Summative content analysis was used to analyze the data. RESULTS: Hesitancy in approaching potential donors, fear about the health of potential LDs, information gaps, language barriers, and challenges evaluating out-of-country donors were highlighted as significant barriers by recipients, and financial concerns and information gaps were identified by donors. Cultural barriers in the SA community were highlighted by donors, recipients, and community members as critical factors when considering donation and transplant; women and elderly SA Canadians highlighted nuanced challenges. Participants reported generally a favorable perception of their health care teams, citing SA representation in the teams as important to providing culturally and linguistically sensitive care. LIMITATIONS: Limited geographic, race, and cultural representation and reliance on virtual data collection. CONCLUSIONS: This study highlights several culturally relevant barriers to donation and transplant that are potentially modifiable through patient-, health system-, and community-focused engagement and education.

Assessing knowledge of end-stage kidney disease and treatment options in hospitalized African American patients undergoing hemodialysis.

OBJECTIVE: African Americans are more likely to develop end-stage kidney disease (ESKD) than whites and face multiple inequities regarding ESKD treatment, renal replacement therapy (RRT), and overall care. This study focused on determining gaps in participants' knowledge of their chronic kidney disease and barriers to RRT selection in an effort to identify how we can improve health care interventions and health outcomes among this population. METHODS: African American participants undergoing hemodialysis were recruited from an ongoing research study of hospitalized patients at an urban Midwest academic medical center. Thirty-three patients were interviewed, and the transcribed interviews were entered into a software program. The qualitative data were coded using template analysis to analyze text and determine key themes. Medical records were used to obtain demographic and additional medical information. RESULTS: Three major themes emerged from the analysis: patients have limited information on ESKD causes and treatments, patients did not feel they played an active role in selecting their initial dialysis unit, and interpersonal interactions with the dialysis staff play a large role in overall unit satisfaction. DISCUSSION: Although more research is needed, this study provides information and suggestions to improve future interventions and care quality, specifically for this population.

Breaking Barriers and Bridging Gaps: Advancing Diversity, Equity, and Inclusion in Kidney Transplant Care for Black and Hispanic Patients in the United States.

Kidney transplantation offers better mortality and quality of life outcomes to patients with end-stage renal failure compared to dialysis. Specifically, living donor kidney transplantation is the best treatment for end-stage renal disease, since it offers the greatest survival benefit compared to deceased donor kidney transplant or dialysis. However, not all patients from all racial/ethnic backgrounds enjoy these benefits. While black and Hispanic patients bear the predominant disease burden within the United States, they represent less than half of all kidney transplants in the country. Other factors such as cultural barriers that proliferate myths about transplant, financial costs that impede altruistic donation, and even biological predispositions create a complex maze and can also perpetuate care inaccessibility. Therefore, blanket efforts to increase the overall donation pool may not extend access to vulnerable populations, who may require more targeted attention and interventions. This review uses US kidney transplantation data to substantiate accessibility differences amongst racial minorities as well as provides examples of successful institutional and national systemic level changes that have improved transplantation outcomes for all.

Validation of the international IgA nephropathy prediction tool in a French cohort beyond 10 years after diagnosis.

INTRODUCTION: The International IgA Nephropathy Network developed a tool (IINN-PT) for predicting the risk of end-stage renal disease (ESRD) or a 50% decline in the estimated glomerular filtration rate (eGFR). We aimed to validate this tool in a French cohort with longer follow-up than previously published validation studies. METHODS: The predicted survival of patients with biopsy-proven immunoglobulin A nephropathy (IgAN) from the Saint Etienne University Hospital cohort was computed with IINN-PT models with or without ethnicity. The primary outcome was the occurrence of either ESRD or a 50% decline in eGFR. The models' performances were evaluated through c-statistics, discrimination and calibration analysis. RESULTS: There were 473 patients with biopsy-proven IgAN, with a median follow-up of 12.4 years. Models with and without ethnicity showed areas under the curve (95% confidence interval) of 0.817 (0.765; 0.869) and 0.833 (0.791; 0.875) and R2D of 0.28 and 0.29, respectively, and an excellent discrimination of groups of increasing predicted risk (P < .001). The calibration analysis was good for both models up to 15 years after diagnosis. The model without ethnicity exhibited a mathematical issue of survival function after 15 years. DISCUSSION: The IINN-PT provided good performances even after 10 years post-biopsy as showed by our study based on a cohort with a longer follow-up than previous cohorts (12.4 versus <6 years). The model without ethnicity exhibited better performances up to 15 years but became aberrant beyond this point due to a mathematical issue affecting the survival function. Our study sheds light on the usefulness of integrating ethnicity as a covariable for prediction of IgAN course.

Race-Based Equations Delayed Black Patients From Getting Onto Kidney Transplant Lists-An Unprecedented New Policy Seeks to Undo the Damage.

This Medical News article is an interview about new policy from the US Organ Procurement and Transplantation Network to address the harms of race-based kidney function estimation.

A Machine Learning Model for Predicting Mortality within 90 Days of Dialysis Initiation.

Background: The first 90 days after dialysis initiation are associated with high morbidity and mortality in end-stage kidney disease (ESKD) patients. A machine learning-based tool for predicting mortality could inform patient-clinician shared decision making on whether to initiate dialysis or pursue medical management. We used the eXtreme Gradient Boosting (XGBoost) algorithm to predict mortality in the first 90 days after dialysis initiation in a nationally representative population from the United States Renal Data System. Methods: A cohort of adults initiating dialysis between 2008-2017 were studied for outcome of death within 90 days of dialysis initiation. The study dataset included 188 candidate predictors prognostic of early mortality that were known on or before the first day of dialysis and was partitioned into training (70%) and testing (30%) subsets. XGBoost modeling used a complete-case set and a dataset obtained from multiple imputation. Model performance was evaluated by c-statistics overall and stratified by subgroups of age, sex, race, and dialysis modality. Results: The analysis included 1,150,195 patients with ESKD, of whom 86,083 (8%) died in the first 90 days after dialysis initiation. The XGBoost models discriminated mortality risk in the nonimputed (c=0.826, 95% CI, 0.823 to 0.828) and imputed (c=0.827, 95% CI, 0.823 to 0.827) models and performed well across nearly every subgroup (race, age, sex, and dialysis modality) evaluated (c>0.75). Across predicted risk thresholds of 10%-50%, higher risk thresholds showed declining sensitivity (0.69-0.04) with improving specificity (0.79-0.99); similarly, positive likelihood ratio was highest at the 40% threshold, whereas the negative likelihood ratio was lowest at the 10% threshold. After calibration using isotonic regression, the model accurately estimated the probability of mortality across all ranges of predicted risk. Conclusions: The XGBoost-based model developed in this study discriminated risk of early mortality after dialysis initiation with excellent calibration and performed well across key subgroups.

Important lack of difference in tacrolimus and mycophenolic acid pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients.

AIM: To examine whether differences in tacrolimus and mycophenolic acid (MPA) pharmacokinetics contribute to the poorer kidney transplant outcomes experienced by Aboriginal Australians. METHODS: Concentration-time profiles for tacrolimus and MPA were prospectively collected from 43 kidney transplant recipients: 27 Aboriginal and 16 Caucasian. Apparent clearance (CL/F) and distribution volume (V/F) for each individual were derived from concentration-time profiles combined with population pharmacokinetic priors, with subsequent assessment for between-group difference in pharmacokinetics. In addition, population pharmacokinetic models were developed using the prospective dataset supplemented by previously developed structural models for tacrolimus and MPA. The change in NONMEM objective function was used to assess improvement in goodness of model fit. RESULTS: No differences were found between Aboriginal and Caucasian groups or empirical Bayes estimates, for CL/F or V/F of MPA or tacrolimus. However, a higher prevalence of CYP3A5 expressers (26% compared with 0%) and wider between-subject variability in tacrolimus CL/F (SD = 5.00 compared with 3.25 L/h/70 kg) were observed in the Aboriginal group, though these differences failed to reach statistical significance (p = .07 and p = .08). CONCLUSION: There were no differences in typical tacrolimus or MPA pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients. This means that Bayesian dosing tools developed to optimise tacrolimus and MPA dosing in Caucasian recipients may be applied to Aboriginal recipients. In turn, this may improve drug exposure and thereby transplant outcomes in this group. Aboriginal recipients appeared to have greater between-subject variability in tacrolimus CL/F and a higher prevalence of CYP3A5 expressers, attributes that have been linked with inferior outcomes.

Reported Cases of End-Stage Kidney Disease - United States, 2000-2019.

End-stage kidney disease (ESKD) (kidney failure requiring dialysis or transplantation) is a costly and disabling condition that often results in premature death (1). During 2019, Medicare fee-for-service expenditures for ESKD were $37.3 billion, accounting for approximately 7% of Medicare paid claims costs (1). Diabetes and hypertension remain the leading causes of ESKD, accounting for 47% and 29%, respectively, of patients who began ESKD treatment in 2019 (1). Compared with White persons, Black, Hispanic, and American Indian or Alaska Native persons are more likely to develop ESKD (1,2) and to have diagnosed diabetes (3). After declining for more than a decade, the incidence rate of ESKD with diabetes reported as the primary cause (ESKD from diabetes) has leveled off since 2010 (1,4). Further, after increasing for many years, the prevalence of diagnosed diabetes has also leveled off (4). Although these flattening trends in rates are important from a population perspective, the trend in the number of ESKD cases is important from a health systems resources perspective. Using United States Renal Data System (USRDS) 2000-2019 data, CDC examined trends in the number of incident and prevalent ESKD cases by demographic characteristics and by primary cause of ESKD. During 2000-2019, the number of incident ESKD cases increased by 41.8%, and the number of prevalent ESKD cases increased by 118.7%. Higher percentage changes in both incident and prevalent ESKD cases were among Asian, Hispanic, and Native Hawaiian or other Pacific Islander persons and among cases with hypertension or diabetes as the primary cause. Interventions to improve care and better manage ESKD risk factors among persons with diabetes and hypertension, along with increased use of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB), and sodium-glucose cotransporter 2 (SGLT2) inhibitors shown to have kidney-protective benefits (5,6) might slow the increase and eventually reverse the trend in incident ESKD cases.

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation.

BACKGROUND: African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. METHODS: Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. RESULTS: Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. CONCLUSION: Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans.

BACKGROUND: α-Globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances α-adrenergic-mediated vasoconstriction. α-Globin gene (HBA) copy number is variable in people of African descent and other populations worldwide. Given the protective effect of nitric oxide in the kidney, we hypothesized that HBA copy number would be associated with kidney disease risk. METHODS: Community-dwelling Black Americans aged ≥45 years old were enrolled in a national longitudinal cohort from 2003 through 2007. HBA copy number was measured using droplet digital PCR. The prevalence ratio (PR) of CKD and the relative risk (RR) of incident reduced eGFR were calculated using modified Poisson multivariable regression. The hazard ratio (HR) of incident ESKD was calculated using Cox proportional hazards multivariable regression. RESULTS: Among 9908 participants, HBA copy number varied from 2 to 6. In analyses adjusted for demographic, clinical, and genetic risk factors, a one-copy increase in HBA was associated with 14% greater prevalence of CKD (PR, 1.14; 95% CI, 1.07 to 1.21; P<0.0001). While HBA copy number was not associated with incident reduced eGFR (RR, 1.06; 95% CI, 0.94 to 1.19; P=0.38), the hazard of incident ESKD was 32% higher for each additional copy of HBA (HR, 1.32; 95% CI, 1.09 to 1.61; P=0.005). CONCLUSIONS: Increasing HBA copy number was associated with a greater prevalence of CKD and incidence of ESKD in a national longitudinal cohort of Black Americans.