Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Changing Education Paradigms: Training Transplant Fellows for High Stake Procedures.

OBJECTIVE: Living kidney donation is a unique operation, as healthy patients are placed at risks inherent with major surgery without physical benefit. The ethical implications associated with any morbidity make it a high-stakes procedure. Fellowships are faced with the dilemma of optimizing fellow training in this demanding procedure while providing safe outcomes to donors. The Laparoscopic Living Donor Nephrectomy (LDN) Workshop is a resource that can provide intense instruction to help bridge the training deficit. Our aim was to examine the course's effectiveness in improving fellows' skill and confidence related to implementing LDN into future practice. METHODS: From 2017 to 2018, 36 abdominal transplant surgery fellows participated in a 2-day workshop consisting of live surgery observation, cadaver lab, and didactic sessions. Surveys were completed precourse, postcourse, and at 3-month postcourse follow-up. RESULTS: Preworkshop, 61% of participants reported less than 50% confidence in independent performance of LDN. Following workshop completion, 95% reported improved confidence. At 3-month follow-up, there was a 30% (p < 0.05) increase in median confidence level. Immediately following the course, 67% reported improved ability to analyze kidneys prior to donation, 74% changed the way donor candidates were evaluated, and 67% reported enhanced ability to risk stratify donors. Eighty-five percent felt it strengthened operative techniques with 70% implementing new diagnostic treatments and surgical strategies. Seventy percent of participants felt it improved their communication with colleagues and 67% had enhanced communication with patients. These trends were maintained at 3-month follow-up. CONCLUSION: These results indicated that the LDN Workshop improves confidence and increases fellows' skillset in a high-stakes procedure. The LDN Workshop is a useful adjunct to fellowship training to optimize successful, efficient, and safe performance of a demanding procedure in a uniquely healthy donor population.

A Donor Utilization Index to Assess the Utilization and Discard of Deceased Donor Kidneys Perceived as High Risk.

BACKGROUND AND OBJECTIVES: An increasing number of patients on the waitlist for a kidney transplant indicates a need to effectively utilize as many deceased donor kidneys as possible while ensuring acceptable outcomes. Assessing regional and center-level organ utilization with regards to discard can reveal regional variation in suboptimal deceased donor kidney acceptance patterns stemming from perceptions of risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We created a weighted donor utilization index from a logistic regression model using high-risk donor characteristics and discard rates from 113,640 deceased donor kidneys procured for transplant from 2010 to 2016, and used it to examine deceased donor kidney utilization in 182 adult transplant centers with >15 annual deceased donor kidney transplants. Linear regression and correlation were used to analyze differences in donor utilization indexes. RESULTS: The donor utilization index was found to significantly vary by Organ Procurement and Transplantation Network region (P<0.001), revealing geographic trends in kidney utilization. When investigating reasons for this disparity, there was no significant correlation between center volume and donor utilization index, but the percentage of deceased donor kidneys imported from other regions was significantly associated with donor utilization for all centers (rho=0.39; P<0.001). This correlation was found to be particularly strong for region 4 (rho=0.83; P=0.001) and region 9 (rho=0.82; P=0.001). Additionally, 25th percentile time to transplant was weakly associated with the donor utilization index (R2=0.15; P=0.03). CONCLUSIONS: There is marked center-level variation in the use of deceased donor kidneys with less desirable characteristics both within and between regions. Broader utilization was significantly associated with shorter time to transplantation.

Regional Disparities in Transplantation With Deceased Donor Kidneys With Kidney Donor Profile Index Less Than 20% Among Candidates With Top 20% Estimated Post Transplant Survival.

INTRODUCTION: The Kidney Allocation System in the United States prioritizes candidates with Estimated Post-Transplant Survival (EPTS) ≤20% to receive deceased donor kidneys with Kidney Donor Profile Index (KDPI) ≤20%. RESEARCH QUESTION: We compared access to KDPI ≤ 20% kidneys for EPTS ≤ 20% candidates across the United States to determine whether geographic disparities in access to these low KDPI kidneys exist. DESIGN: We identified all incident adult deceased donor kidney candidates wait-listed January 1, 2015, to March 31, 2018, using United Network for Organ Sharing data. We calculated the proportion of candidates transplanted, final EPTS, and KDPI of transplanted kidneys for candidates listed with EPTS ≤ 20% versus >20%. We compared the odds of receiving a KDPI ≤ 20% deceased donor kidney for EPTS ≤ 20% candidates across regions using logistic regression. RESULTS: Among 121 069 deceased donor kidney candidates, 28.5% had listing EPTS ≤ 20%. Of these, 16.1% received deceased donor kidney transplants (candidates listed EPTS > 20%: 17.1% transplanted) and 12.3% lost EPTS ≤ 20% status. Only 49.4% of transplanted EPTS ≤ 20% candidates received a KDPI ≤ 20% kidney, and 48.3% of KDPI ≤ 20% kidneys went to recipients with EPTS > 20% at the time of transplantation. Odds of receiving a KDPI ≤ 20% kidney were highest in region 6 and lowest in region 9 (odds ratio 0.19 [0.13 to 0.28]). The ratio of KDPI ≤ 20% donors per EPTS ≤ 20% candidate and likelihood of KDPI ≤ 20% transplantation were strongly correlated (r2 = 0.84). DISCUSSION: Marked geographic variation in the likelihood of receiving a KDPI ≤ 20% deceased donor kidney among transplanted EPTS ≤ 20% candidates exists and is related to differences in organ availability within allocation borders. Policy changes to improve organ sharing are needed to improve equity in access to low KDPI kidneys.

Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function.

BACKGROUND: Relationship between live donor renal anatomic asymmetry and posttransplant recipient function has not been studied extensively. METHODS: We analyzed 96 live kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from computerized tomography angiograms) and their matching recipients. Split function differences (SFD) were quantified with technetium-dimercaptosuccinic acid renography. Implantation biopsies at time 0 were semiquantitatively scored. A comprehensive model using donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at 1 year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60 mL/min/1.73 m(2) at 1 year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the chronic kidney disease-epidemiology collaboration formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). RESULTS: In the study cohort, the mean Vol/Wgt and eGFR at 1 year were 2.04 mL/kg and 60.4 mL/min/1.73 m(2), respectively. Volume and split ratios between 2 donor kidneys were strongly correlated (r = 0.79, P < 0.001). The biopsy scores among SFD categories (<5%, 5%-10%, >10%) were not different (P = 0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR > 60 mL/min/1.73 m (odds ratio, 8.94, 95% CI 2.47-32.25, P = 0.001) and had a strong discriminatory power in predicting the risk of eGFR less than 60 mL/min/1.73 m(2) at 1 year [receiver operating curve (ROC curve), 0.78, 95% CI, 0.68-0.89]. CONCLUSIONS: In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at 1 year after transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.

Variation in structure and delivery of care between kidney transplant centers in the United States.

Although the United States possesses one of the most comprehensive transplant registries in the world, nationally representative data on how transplant care is structured and delivered is lacking. Therefore, we surveyed all 208 adult kidney transplant centers in the United States, excluding 37 pediatric and 58 inactive adult centers. Respondents were asked about the characteristics of their kidney transplant programs (25 items), the structure and process of care (18 items), coordination of care (10 items), and the characteristics of transplant physicians and surgeons (9 items). The survey was completed by directors of 156 transplant centers (75% response). The results demonstrated significant variation between centers in several domains. Sixty-five percent of transplant centers do not have a dedicated transplant pharmacist in outpatient care. Two thirds of transplant centers do not see the kidney transplant recipients at least monthly during the first year. Less than 30% of centers perform joint sit-down or walking rounds between nephrology and transplant surgery. There was significant variation in the structure and process of care in kidney transplantation. This implies variation in the use of resources at the transplant centers. This variation should be studied to determine best practices associated with optimal kidney allograft and patient survival.

Preformed donor-specific antibodies and risk of antibody-mediated rejection in repeat renal transplantation.

BACKGROUND: Allograft outcomes in patients undergoing repeat renal transplantation are inferior compared to first-time transplant recipient outcomes. Donor-specific antibodies detected by solid-phase assays (DSA-SPA) may contribute to the worse prognosis. The influence of DSA-SPA on repeat renal transplantation outcomes has not been previously studied in detail. DESIGN: This study reports the findings in 174 patients who underwent repeat renal transplantation between years 2007 and 2012. These included 62 patients with preformed DSA-SPA detected by Luminex at the time of transplantation. Patients received standard and consistent immunosuppression and were monitored closely for evidence of rejection. Recipients who underwent desensitization were excluded from this analysis. Endpoints included development of biopsy-proven acute rejection and analysis of graft survival and function. RESULTS: Patients in the DSA-SPA-positive and DSA-SPA-negative groups received similar immunosuppression, and a similar proportion of recipients had a peak panel reactive antibody greater than 20%; the two groups differed with respect to human leukocyte antigen mismatches (4.7 ± 1.1 vs. 4.1 ± 1.7, P=0.024). Recipients with preformed DSA-SPA had higher rejection rates (54.8% vs. 34.8%, P=0.01), including higher rates of antibody-mediated rejection (AMR) (32.3% vs. 7.1%, P<0.001). Recipients who were DSA-SPA-positive and flow cytometry crossmatch (FCXM)-positive had a higher incidence of both AMR (OR 4.6, P=0.009) and of acute rejection (OR 3.57, P=0.02) as compared to those who were DSA-SPA-positive and FCXM-negative. Overall allograft survival was similar in the DSA-SPA-positive and DSA-SPA-negative groups (log-rank test=0.63, P=0.428). Differences in allograft function were detectable after 2 years (32.8 ± 13.1 vs. 47 ± 20.2 mL/min/1.73 m(2), P=0.023) and may be reflective of more AMR among DSA-SPA-positive patients. CONCLUSIONS: This analysis suggests that DSA-SPA increases the overall risk of acute rejection but does not appear to adversely impact allograft survival during the early follow-up period. Close monitoring of renal function and early biopsy for AMR detection appear to allow for satisfactory short-term allograft outcomes in repeat transplant recipients.

Columbia University/New York-Presbyterian Hospital: improving access to renal transplantation.

There continues to be an increasing disparity between organ supply and demand in kidney transplantation with over 87,000 patients currently on the waiting list. Prolonged waiting times on dialysis is associated with significant morbidity and mortality rates. At Columbia University Medical Center/New York-Presbyterian Hospital we have implemented several strategies to improve access to transplantation. Here we present these key steps that have resulted in a significant reduction in our median waiting times and successfully increased the rate of transplantation at our center.

Consensus opinion from the antibody working group on the diagnosis, reporting, and risk assessment for antibody-mediated rejection and desensitization protocols.

During the past few decades, much of the experimental and clinical effort in solid-organ transplantation has been directed toward ameliorating or abrogating T-cell-mediated responses. As a result, universally understood and accepted nomenclature and diagnostic criteria have evolved. Humoral immunity in transplantation has yet to undergo a similar renaissance. Readers of transplant journals regularly find it difficult and often impossible to interpret data on the diagnosis and management of antibody-mediated rejection. The Antibody Working Group was assembled in an attempt to provide guidelines for the standardization of nomenclature, diagnostic criteria, reporting, antibody profiling, and risk assessment.

Race and trust in the health care system.

OBJECTIVE: A legacy of racial discrimination in medical research and the health care system has been linked to a low level of trust in medical research and medical care among African Americans. While racial differences in trust in physicians have been demonstrated, little is known about racial variation in trust of health insurance plans and hospitals. For the present study, the authors analyzed responses to a cross-sectional telephone survey to assess the independent relationship of self-reported race (non-Hispanic black or non-Hispanic white) with trust in physicians, hospitals, and health insurance plans. METHODS: Respondents ages 18-75 years were asked to rate their level of trust in physicians, health insurance plans, and hospitals. Items from the Medical Mistrust Index were used to assess fear and suspicion of hospitals. RESULTS: Responses were analyzed for 49 (42%) non-Hispanic black and 69 (58%) non-Hispanic white respondents (N=118; 94% of total survey population). A majority of respondents trusted physicians (71%) and hospitals (70%), but fewer trusted their health insurance plans (28%). After adjustment for potential confounders, non-Hispanic black respondents were less likely to trust their physicians than non-Hispanic white respondents (adjusted absolute difference 37%; p=0.01) and more likely to trust their health insurance plans (adjusted absolute difference 28%; p=0.04). The difference in trust of hospitals (adjusted absolute difference 13%) was not statistically significant. Non-Hispanic black respondents were more likely than non-Hispanic white respondents to be concerned about personal privacy and the potential for harmful experimentation in hospitals. CONCLUSIONS: Patterns of trust in components of our health care system differ by race. Differences in trust may reflect divergent cultural experiences of blacks and whites as well as differences in expectations for care. Improved understanding of these factors is needed if efforts to enhance patient access to and satisfaction with care are to be effective.

The general public's concerns about clinical risk in live kidney donation.

Difficulty in attracting live kidney donors may be related to fears regarding both the surgical procedure for kidney harvesting and future failure of the remaining kidney. We conducted a cross-sectional study of households in Maryland to identify public disincentives to living related kidney donation. In multivariate analyses, we assessed the independent effects of several factors on willingness to donate a kidney to a sibling. We also assessed thresholds for factors above which persons would not donate a kidney. Of 385 participants, 66% were extremely willing to donate to a sibling. After adjustment, those who considered the length of a hospital stay, out-of-pocket expenses, size and appearance of a scar, the time it takes to get to the transplant center, and the donor risk of developing kidney failure very important had 50-60% less odds of being extremely willing to donate. Median acceptable levels for risk of complications, hospital stay, compensated and uncompensated time from work, time requiring pain medications, and out-of-pocket expenses were greater than levels from clinical evidence regarding both laparoscopic and open nephrectomy. Unrealistic concerns among the general public regarding live donation may serve as potential disincentives to donation. Efforts to educate the public regarding live donation might help assuage fears and attract those who may not otherwise donate.

Determinants of willingness to donate living related and cadaveric organs: identifying opportunities for intervention.

BACKGROUND: Although low rates of cadaveric organ donation have been attributed to potential cadaveric donors' concerns regarding their religious beliefs and mistrust of the health care system, it is unclear whether similar concerns are important to potential living related donors. It is also not known which factors might be most responsible for low rates of cadaveric and living related donation among the general public. METHODS: We conducted a cross-sectional study of households in Maryland, using a standardized telephone questionnaire, to assess factors associated with willingness to donate cadaveric and living related organs. We compared factors (demographic, cultural, attitudinal, and clinical) related to willingness to donate cadaveric organs with factors related to willingness to donate living related organs. In multivariate analyses, we assessed the independent relation of factors to willingness to donate cadaveric and living related organs, and we assessed the relative importance of these factors in explaining variation in the general public's willingness to donate. RESULTS: Of 385 participants (84% of randomized homes), 254 (66%) were extremely willing to donate to a sibling but only 179 (47%) had designated themselves a cadaveric donor on their drivers' licenses. In bivariate analysis, older age, comorbid conditions, mistrust in hospitals, and concerns about discrimination in hospitals were statistically significantly associated with less willingness to donate living related organs, although African-Americans, older age, lower education, lack of insurance, unemployment, comorbid conditions, and religion/spirituality were associated with less willingness to donate cadaveric organs. After adjusting for potential confounders, only mistrust in hospitals and concerns about discrimination remained strongly and independently associated with 50 to 60% less odds of willingness to donate living related organs [[relative odds [95% confidence intervals (CI)]: 0.4 (0.2-0.7) to 0.5 (0.3-1.0) and 0.4 (0.2-0.9), respectively]] although presence of dependents was associated with 70% higher odds of willingness to donate living related organs [relative odds (95% CI): 1.7 (1.0-3.0)]. In contrast, older age, employment status, religion/spirituality, and mistrust in hospitals were associated with 50 to 90% less odds of willingness to donate living related organs cadaveric organs [relative odds (95% CI): 0.3 (0.1-0.8), 0.4(0.2-0.8), 0.1 (0.1- 0.5) to 0.5 (0.2-0.9), and 0.3 (0.2-0.6), respectively]. Mistrust in hospitals and concerns about the surgical donation procedure contributed most to the variation in willingness to be a living related donor, although race contributed most to the variation in willingness to be a cadaveric donor. CONCLUSIONS: Many factors affect the general public's willingness to donate organs, but their relative contribution is different for living related versus cadaveric donation. Efforts to improve organ donation rates should be directed toward factors that are most important in explaining the existing variation in willingness to donate.

Understanding disparities in donor behavior: race and gender differences in willingness to donate blood and cadaveric organs.

BACKGROUND: Recent efforts to recruit blood and organ donors have only marginally improved demographic disparities in willingness to donate. Few studies have examined which factors are most important in explaining race and gender disparities in willingness to donate. OBJECTIVES: To assess race and gender differences in willingness to donate blood and cadaveric organs, and to determine the extent to which several factors (including sociodemographic characteristics and attitudes about religion and mistrust of hospitals) might explain differences in willingness to donate. RESEARCH DESIGN: Cross-sectional telephone survey of Maryland households contacted via random-digit dialing. MEASURES: Past blood donation, organ-donor status on driver's license, and measures of medical mistrust and religious and spiritual salience. SUBJECTS: Persons age 18 to 75 living in the Baltimore, Maryland metropolitan area. RESULTS: Of 385 respondents (84% of randomized households), 114 were black females, 46 were black males, 110 were white females, and 69 were white males. Before adjustment, black females were least willing to donate blood (41%), and black males were least willing to become cadaveric donors (19%) among all race-gender groups. Adjustment for respondent concerns about mistrust of hospitals and discrimination in hospitals explained most differences in willingness to donate blood, whereas adjustment for respondents' beliefs regarding the importance of spirituality and religion explained most differences in willingness to donate cadaveric organs. CONCLUSIONS: Both race and gender are important identifiers of those less willing to donate. To maximize efficiency, donor recruitment efforts should focus on race-gender groups with lowest levels of willingness. Potential donor concerns regarding mistrust in hospitals and religion/spirituality may serve as important issues to address when developing programs to improve donation rates.