Failure to Advance Access to Kidney Transplantation over Two Decades in the United States.

BACKGROUND: Extensive research and policies have been developed to improve access to kidney transplantation among patients with ESKD. Despite this, wide variation in transplant referral rates exists between dialysis facilities. METHODS: To evaluate the longitudinal pattern of access to kidney transplantation over the past two decades, we conducted a retrospective cohort study of adult patients with ESKD initiating ESKD or placed on a transplant waiting list from 1997 to 2016 in the United States Renal Data System. We used cumulative incidence models accounting for competing risks and multivariable Cox models to evaluate time to waiting list placement or transplantation (WLT) from ESKD onset. RESULTS: Among the study population of 1,309,998 adult patients, cumulative 4-year WLT was 29.7%, which was unchanged over five eras. Preemptive WLT (prior to dialysis) increased by era (5.2% in 1997-2000 to 9.8% in 2013-2016), as did 4-year WLT incidence among patients aged 60-70 (13.4% in 1997-2000 to 19.8% in 2013-2016). Four-year WLT incidence diminished among patients aged 18-39 (55.8%-48.8%). Incidence of WLT was substantially lower among patients in lower-income communities, with no improvement over time. Likelihood of WLT after dialysis significantly declined over time (adjusted hazard ratio, 0.80; 95% confidence interval, 0.79 to 0.82) in 2013-2016 relative to 1997-2000. CONCLUSIONS: Despite wide recognition, policy reforms, and extensive research, rates of WLT following ESKD onset did not seem to improve in more than two decades and were consistently reduced among vulnerable populations. Improving access to transplantation may require more substantial interventions.

COVID-19 mortality among kidney transplant candidates is strongly associated with social determinants of health.

The COVID-19 pandemic has affected all portions of the global population. However, many factors have been shown to be particularly associated with COVID-19 mortality including demographic characteristics, behavior, comorbidities, and social conditions. Kidney transplant candidates may be particularly vulnerable to COVID-19 as many are dialysis-dependent and have comorbid conditions. We examined factors associated with COVID-19 mortality among kidney transplant candidates from the National Scientific Registry of Transplant Recipients from March 1 to December 1, 2020. We evaluated crude rates and multivariable incident rate ratios (IRR) of COVID-19 mortality. There were 131 659 candidates during the study period with 3534 all-cause deaths and 384 denoted a COVID-19 cause (5.00/1000 person years). Factors associated with increased COVID-19 mortality included increased age, males, higher body mass index, and diabetes. In addition, Blacks (IRR = 1.96, 95% C.I.: 1.43-2.69) and Hispanics (IRR = 3.38, 95% C.I.: 2.46-4.66) had higher COVID-19 mortality relative to Whites. Patients with lower educational attainment, high school or less (IRR = 1.93, 95% C.I.: 1.19-3.12, relative to post-graduate), Medicaid insurance (IRR = 1.73, 95% C.I.: 1.26-2.39, relative to private), residence in most distressed neighborhoods (fifth quintile IRR = 1.93, 95% C.I.: 1.28-2.90, relative to first quintile), and most urban and most rural had higher adjusted rates of COVID-19 mortality. Among kidney transplant candidates in the United States, social determinants of health in addition to demographic and clinical factors are significantly associated with COVID-19 mortality.

Expanding clarity or confusion? Volatility of the 5-tier ratings assessing quality of transplant centers in the United States.

Outcomes of patients receiving solid organ transplants in the United States are systematically aggregated into bi-annual Program-Specific Reports (PSRs) detailing risk-adjusted survival by transplant center. Recently, the Scientific Registry of Transplant Recipients (SRTR) issued 5-tier ratings evaluating centers based on risk-adjusted 1-year graft survival. Our primary aim was to examine the reliability of 5-tier ratings over time. Using 10 consecutive PSRs for adult kidney transplant centers from June 2012 to December 2016 (n = 208), we applied 5-tier ratings to center outcomes and evaluated ratings over time. From the baseline period (June 2012), 47% of centers had at least a 1-unit tier change within 6 months, 66% by 1 year, and 94% by 3 years. Similarly, 46% of centers had at least a 2-unit tier change by 3 years. In comparison, 15% of centers had a change in the traditional 3-tier rating at 3 years. The 5-tier ratings at 4 years had minimal association with baseline rating (Kappa 0.07, 95% confidence interval [CI] -0.002 to 0.158). Centers had a median of 3 different 5-tier ratings over the period (q1 = 2, q3 = 4). Findings were consistent for center volume, transplant rate, and baseline 5-tier rating. Cumulatively, results suggest that 5-tier ratings are highly volatile, limiting their utility for informing potential stakeholders, particularly transplant candidates given expected waiting times between wait listing and transplantation.

Residential Area Life Expectancy: Association With Outcomes and Processes of Care for Patients With ESRD in the United States.

BACKGROUND: The effects of underlying noncodified risks are unclear on the prognosis of patients with end-stage renal disease (ESRD). We aimed to evaluate the association of residential area life expectancy with outcomes and processes of care for patients with ESRD in the United States. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult patients with incident ESRD between 2006 and 2013 recorded in the US Renal Data System (n=606,046). PREDICTOR: The primary exposure was life expectancy in the patient's residential county estimated by the Institute for Health Metrics and Evaluation. OUTCOMES: Death, placement on the kidney transplant wait list, living and deceased donor kidney transplantation, and posttransplantation graft loss. RESULTS: Median life expectancies of patients' residences were 75.6 (males) and 80.4 years (females). Compared to the highest life expectancy quintile and adjusted for demographic factors, disease cause, and multiple comorbid conditions, the lowest quintile had adjusted HRs for mortality of 1.20 (95% CI, 1.18-1.22); placement onto the waiting list, 0.68 (95% CI, 0.67-0.70); living donor transplantation, 0.53 (95% CI, 0.51-0.56); posttransplantation graft loss, 1.35 (95% CI, 1.27-1.43); and posttransplantation mortality, 1.29 (95% CI, 1.19-1.39). Patients living in areas with lower life expectancy were less likely to be informed about transplantation, be under the care of a nephrologist, or receive an arteriovenous fistula as the initial dialysis access. Results remained consistent with additional adjustment for zip code-level median income, population size, and urban-rural locality. LIMITATIONS: Potential residual confounding and attribution of effects to individuals based on residential area-level data. CONCLUSIONS: Residential area life expectancy, a proxy for socioeconomic, environmental, genetic, and behavioral factors, was independently associated with mortality and process-of-care measures for patients with ESRD. These results emphasize the underlying effect on health outcomes of the environment in which patients live, independent of patient-level factors. These findings may have implications for provider assessments.

NCI think tank concerning the identifiability of biospecimens and "omic" data.

PURPOSE: On 11 and 12 June 2012, the National Cancer Institute hosted a think tank concerning the identifiability of biospecimens and "omic" data in order to explore challenges surrounding this complex and multifaceted topic. METHODS: The think tank brought together 46 leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. RESULTS: The first day involved presentations regarding the state of the science of reidentification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry, and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small breakout groups designed to address specific subtopics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research. CONCLUSION: We describe the outcomes of this 2-day meeting, including two complementary themes that emerged from moderated discussions following the presentations on day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability.

Development of a prolonged warm ex vivo perfusion model for kidneys donated after cardiac death.

PURPOSE: Ex vivo perfusion of marginal kidney grafts offers the chance to expand the donor pool, but there is no current clinical standard for the prolonged warm perfusion of renal grafts. This exploratory pilot study seeks to identify a stable ex vivo kidney perfusion model that can support low intravascular resistance and preserve histologic architecture in a porcine donation after cardiac death (DCD) model. METHODS: 15 kidneys were preserved in 1 of 3 settings: normothermic whole blood (NT-WB), normothermic Steen Solution™ (XVIVO Perfusion) with whole blood (NT-Steen/WB), or subnormothermic Steen Solution™ at 21°C (SNT-Steen). Kidneys were primarily assessed using hemodynamic parameters and histologic analysis. RESULTS: NT-WB perfusion resulted in high vascular resistance and glomerular necrosis. NT-Steen/WB and SNT-Steen resistance ranged between 0.18-0.45 mmHg/mL per minute and 0.25-0.53 mmHg/mL per minute, respectively, enabling stable perfusion for up to 24 hours. NT-Steen/WB demonstrated tubular and glomerular necrosis, while the histologic architecture of SNT-Steen was preserved with the exception of numerous proteinaceous casts. CONCLUSIONS: Our results suggest that ex vivo kidney perfusion with Steen Solution™ at 21°C supports low and stable vascular resistance and provides adequate histologic preservation during 24-hour perfusion.

Evaluation of Flagging Criteria of United States Kidney Transplant Center Performance: How to Best Define Outliers?

BACKGROUND: Scientific Registry of Transplant Recipients report cards of US organ transplant center performance are publicly available and used for quality oversight. Low center performance (LP) evaluations are associated with changes in practice including reduced transplant rates and increased waitlist removals. In 2014, Scientific Registry of Transplant Recipients implemented new Bayesian methodology to evaluate performance which was not adopted by Center for Medicare and Medicaid Services (CMS). In May 2016, CMS altered their performance criteria, reducing the likelihood of LP evaluations. METHODS: Our aims were to evaluate incidence, survival rates, and volume of LP centers with Bayesian, historical (old-CMS) and new-CMS criteria using 6 consecutive program-specific reports (PSR), January 2013 to July 2015 among adult kidney transplant centers. RESULTS: Bayesian, old-CMS and new-CMS criteria identified 13.4%, 8.3%, and 6.1% LP PSRs, respectively. Over the 3-year period, 31.9% (Bayesian), 23.4% (old-CMS), and 19.8% (new-CMS) of centers had 1 or more LP evaluation. For small centers (<83 transplants/PSR), there were 4-fold additional LP evaluations (52 vs 13 PSRs) for 1-year mortality with Bayesian versus new-CMS criteria. For large centers (>183 transplants/PSR), there were 3-fold additional LP evaluations for 1-year mortality with Bayesian versus new-CMS criteria with median differences in observed and expected patient survival of -1.6% and -2.2%, respectively. CONCLUSIONS: A significant proportion of kidney transplant centers are identified as low performing with relatively small survival differences compared with expected. Bayesian criteria have significantly higher flagging rates and new-CMS criteria modestly reduce flagging. Critical appraisal of performance criteria is needed to assess whether quality oversight is meeting intended goals and whether further modifications could reduce risk aversion, more efficiently allocate resources, and increase transplant opportunities.

Emergency Department Visits after Kidney Transplantation.

BACKGROUND AND OBJECTIVES: In 2011, there were approximately 131 million visits to an emergency department in the United States. Emergency department visits have increased over time, far outpacing growth of the general population. There is a paucity of data evaluating emergency department visits among kidney transplant recipients. We sought to evaluate the incidence and risk factors for emergency department visits after initial hospital discharge after transplantation in the United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified 10,533 kidney transplant recipients from California, New York, and Florida between 2009 and 2012 using the State Inpatient and Emergency Department Databases included in the Healthcare Cost and Utilization Project. We used multivariable Poisson and Cox proportional hazard models to evaluate adjusted incidence rates and time to emergency department visits after transplantation. RESULTS: There were 17,575 emergency department visits over 13,845 follow-up years (overall rate =126.9/100 patient-years; 95% confidence interval, 125.1 to 128.8). The cumulative incidences of emergency department visits at 1, 12, and 24 months were 12%, 40%, and 57%, respectively, with median time =19 months; 48% of emergency department visits led to hospital admission. Risk factors for higher emergency department rates included younger age, women, black and Hispanic race/ethnicity, public insurance, depression, diabetes, peripheral vascular disease, and emergency department use before transplant. There was wide variation in emergency department visits by individual transplant center (10th percentile =70.0/100 patient-years; median =124.6/100 patient-years; and 90th percentile =187.4/100 patient-years). CONCLUSIONS: The majority of kidney transplant recipients will visit an emergency department in the first 2 years post-transplantation, with significant variation by patient characteristics and individual centers. As such, coordination of care through the emergency department is a critical component of post-transplant management, and specific acumen of transplant-related care is needed among emergency department providers. Additional research assessing best processes of care for post-transplant management and health care expenditures and outcomes associated with emergency department visits for transplant recipients are warranted.

Association between kidney transplant center performance and the survival benefit of transplantation versus dialysis.

BACKGROUND AND OBJECTIVES: Despite the benefits of kidney transplantation, the total number of transplants performed in the United States has stagnated since 2006. Transplant center quality metrics have been associated with a decline in transplant volume among low-performing centers. There are concerns that regulatory oversight may lead to risk aversion and lack of transplantation growth. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective cohort study of adults (age≥18 years) wait-listed for kidney transplantation in the United States from 2003 to 2010 using the Scientific Registry of Transplant Recipients was conducted. The primary aim was to investigate whether measured center performance modifies the survival benefit of transplantation versus dialysis. Center performance was on the basis of the most recent Scientific Registry of Transplant Recipients evaluation at the time that patients were placed on the waiting list. The primary outcome was the time-dependent adjusted hazard ratio of death compared with remaining on the transplant waiting list. RESULTS: Among 223,808 waitlisted patients, 59,199 and 32,764 patients received a deceased or living donor transplant, respectively. Median follow-up from listing was 43 months (25th percentile=25 months, 75th percentile=67 months), and there were 43,951 total patient deaths. Deceased donor transplantation was independently associated with lower mortality at each center performance level compared with remaining on the waiting list; adjusted hazard ratio was 0.24 (95% confidence interval, 0.21 to 0.27) among 11,972 patients listed at high-performing centers, adjusted hazard ratio was 0.32 (95% confidence interval, 0.31 to 0.33) among 203,797 patients listed at centers performing as expected, and adjusted hazard ratio was 0.40 (95% confidence interval, 0.35 to 0.45) among 8039 patients listed at low-performing centers. The survival benefit was significantly different by center performance (P value for interaction <0.001). CONCLUSIONS: Findings indicate that measured center performance modifies the survival benefit of kidney transplantation, but the benefit of transplantation remains highly significant even at centers with low measured quality. Policies that concurrently emphasize improved center performance with access to transplantation should be prioritized to improve ESRD population outcomes.

Hospitalizations following living donor nephrectomy in the United States.

BACKGROUND AND OBJECTIVES: Living donors represented 43% of United States kidney donors in 2012. Although research suggests minimal long-term consequences of donation, few comprehensive longitudinal studies for this population have been performed. The primary aims of this study were to examine the incidence, risk factors, and causes of rehospitalization following donation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: State Inpatient Databases (SID) compiled by the Agency for Healthcare Research and Quality were used to identify living donors in four different states between 2005 and 2010 (n=4524). Multivariable survival models were used to examine risks for rehospitalization, and patient characteristics were compared with data from the Scientific Registry of Transplant Recipients (SRTR). Outcomes among patients undergoing appendectomy (n=200,274), cholecystectomy (n=255,231), and nephrectomy for nonmetastatic carcinoma (n=1314) were contrasted. RESULTS: The study population was similar to United States donors (for SRTR and SID, respectively: mean age, 41 and 41 years; African Americans, 12% and 10%; women, 60% and 61%). The 3-year incidence of rehospitalization following donation was 11% for all causes and 9% excluding pregnancy-related hospitalizations. After censoring of models for pregnancy-related rehospitalizations, older age (adjusted hazard ratio [AHR], 1.02 per year; 95% confidence interval [95% CI], 1.01 to 1.03), African American race (AHR, 2.16; 95% CI, 1.54 to 3.03), depression (AHR, 1.88; 95% CI, 1.12 to 3.14), hypothyroidism (AHR, 1.63; 95% CI, 1.06 to 2.49), and longer initial length of stay were related to higher rehospitalization rates among donors. Compared with living donors, adjusted risks for rehospitalizations were greater among patients undergoing appendectomy (AHR, 1.58; 95% CI, 1.42 to 1.75), cholecystectomy (AHR, 2.25; 95% CI, 2.03 to 2.50), and nephrectomy for nonmetastatic carcinoma (AHR, 2.95; 95% CI, 2.58 to 3.37). Risks for rehospitalizations were higher among African Americans than whites in each of the surgical groups. CONCLUSIONS: The SID is a valuable source for evaluating characteristics and outcomes of living kidney donors that are not available in traditional transplant databases. Rehospitalizations following donor nephrectomy are less than seen with other comparable surgical procedures but are relatively higher among donors who are older, are African American, and have select comorbid conditions. The increased risks for rehospitalizations among African Americans are not unique to living donation.

Comorbidity burden and perioperative complications for living kidney donors in the United States.

BACKGROUND AND OBJECTIVES: Since 1998, 35% of kidney transplants in the United States have been derived from living donors. Research suggests minimal long-term health consequences after donation, but comprehensive studies are limited. The primary objective was to evaluate trends in comorbidity burden and complications among living donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The National Inpatient Sample (NIS) was used to identify donors from 1998 to 2010 (n=69,117). Comorbid conditions, complications, and length of stay during hospitalization were evaluated. Outcomes among cohorts undergoing appendectomies, cholecystectomies and nephrectomy for nonmetastatic carcinoma were compared, and sample characteristics were validated with the Scientific Registry of Transplant Recipients (SRTR). Survey regression models were used to identify risk factors for outcomes. RESULTS: The NIS captured 89% (69,117 of 77,702) of living donors in the United States. Donor characteristics were relatively concordant with those noted in SRTR (mean age, 40.1 versus 40.3 years [P=0.18]; female donors, 59.0% versus 59.1% [P=0.13]; white donors, 68.4% versus 69.8% [P<0.001] for NIS versus SRTR). Incidence of perioperative complications was 7.9% and decreased from 1998 to 2010 (from 10.1% to 7.6%). Men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 1.20 to 1.56) and donors with hypertension (AOR, 3.35; 95% CI, 2.24 to 5.01) were more likely to have perioperative complications. Median length of stay declined over time (from 3.7 days to 2.5 days), with longer length of stay associated with obesity, depression, hypertension, and pulmonary disorders. Presence of depression (AOR, 1.08; 95% CI, 1.04 to 1.12), hypothyroidism (AOR, 1.07; 95% CI, 1.04 to 1.11), hypertension (AOR, 1.38; 95% CI, 1.27 to 1.49), and obesity (AOR, 1.07; 95% CI, 1.03 to 1.11) increased over time. Complication rates and length of stay were similar for patients undergoing appendectomies and cholecystectomies but were less than those with nephrectomies for carcinoma. CONCLUSIONS: The NIS is a representative sample of living donors. Complications and length of stay after donation have declined over time, while presence of documented comorbid conditions has increased. Patients undergoing appendectomy and cholecystectomy have similar outcomes during hospitalization. Monitoring the health of living donors remains critically important.

The association of community health indicators with outcomes for kidney transplant recipients in the United States.

OBJECTIVE: To evaluate the association of community health indicators with outcomes for kidney transplant recipients. DESIGN: Retrospective observational cohort study using multivariable Cox proportional hazards models. SETTING: Transplant recipients in the United States from the Scientific Registry of Transplant Recipients merged with health indicators compiled from several national databases and the Centers for Disease Control and Prevention, including the National Center for Health Statistics, the Behavioral Risk Factor Surveillance System, and the National Center for Chronic Disease Prevention and Health Promotion. PATIENTS: A total of 100 164 living and deceased donor adult (aged 18 years) kidney transplant recipients who underwent a transplant between January 1, 2004, and December 31, 2010. MAIN OUTCOME MEASURES: Risk-adjusted time to posttransplant mortality and graft loss. RESULTS: Multiple health indicators from recipients' residence were independently associated with outcomes, including low birth weight, preventable hospitalizations, inactivity rate, and smoking and obesity prevalence. Recipients in the highest-risk counties were more likely to be African American (adjusted odds ratio, 1.59, 95% CI, 1.51-1.68), to be younger (aged 18-39 years; 1.46; 1.32-1.60), to have lower educational attainment (

Patient participation in research among solid organ transplant recipients in the United States.

BACKGROUND: In many healthcare contexts, evidence exists that patients who participate in research protocols (PRP) significantly differ from nonparticipants. These differences may affect the external validity of study findings, reflect access to care, and potentially explain sources of difference in patient outcomes. There is no comprehensive study evaluating PRP among transplant recipients. METHODS: We evaluated the national Scientific Registry of Transplant Recipients from 2000 to 2008 for liver, kidney, heart, lung, and simultaneous pancreas/kidney transplant recipients in the United States for which PRP for immunosuppressive medications is reported at follow-up. Our primary aims were to evaluate participant characteristics, compare outcomes between participants and nonparticipants, and assess variability of PRP between centers and medications. RESULTS: The national proportions of PRP at 1 year by organ were kidney (8.2%), liver (2.9%), heart (5.0%), lung (2.6%), and simultaneous pancreas/kidney (2.8%). Factors associated with PRP included recipients' educational attainment, insurance, race/ethnicity, gender and age, donor age, transplant number, income, distance to center, and center volume. Graft and patient survivals were significantly higher among PRP for kidney, liver, and lung transplant recipients. PRP varied markedly between centers (range, 0%-58%) and by immunosuppressant medications. CONCLUSIONS: There are systematic differences between participants and nonparticipants in research in the transplant population that may affect the external validity of research findings. Superior outcomes among participants may suggest that participation in research itself affords certain benefits. Future research evaluating the mechanisms for differential participation rates and improved survival among participants is needed.

Toward a construct definition of informed consent comprehension.

VARIATION IN HOW INFORMED CONSENT comprehension tests have been developed may be largely due to the absence of a standardized construct definition. Developing a construct definition would provide a standardized framework for determining how an instrument should be constructed, implemented, interpreted, and applied. Therefore, we utilized the Delphi consensus approach with an international expert panel (N = 19) to gather knowledge, opinions and eventually consensus for a construct definition. Expert consensus was achieved after three revision cycles. While acknowledging that there are limitations to this study, it nonetheless should be considered as a step toward standardization of a construct definition of informed consent comprehension.