Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities.

Background: Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities. Methods: We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death. Results: We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10). Conclusions: Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

The Medical Costs of Determining Eligibility and Waiting for a Kidney Transplantation.

BACKGROUND: Recent efforts to increase access to kidney transplant (KTx) in the United States include increasing referrals to transplant programs, leading to more pretransplant services. Transplant programs reconcile the costs of these services through the Organ Acquisition Cost Center (OACC). OBJECTIVE: The aim of this study was to determine the costs associated with pretransplant services by applying microeconomic methods to OACC costs reported by transplant hospitals. RESEARCH DESIGN, SUBJECTS, AND MEASURES: For all US adult kidney transplant hospitals from 2013 through 2018 (n=193), we crosslinked the total OACC costs (at the hospital-fiscal year level) to proxy measures of volumes of pretransplant services. We used a multiple-output cost function, regressing total OACC costs against proxy measures for volumes of pretransplant services and adjusting for patient characteristics, to calculate the marginal cost of each pretransplant service. RESULTS: Over 1015 adult hospital-years, median OACC costs attributable to the pretransplant services were $5 million. Marginal costs for the pretransplant services were: initial transplant evaluation, $9k per waitlist addition; waitlist management, $2k per patient-year on the waitlist; deceased donor offer management, $1k per offer; living donor evaluation, procurement and follow-up: $26k per living donor. Longer time on dialysis among patients added to the waitlist was associated with higher OACC costs at the transplant hospital. CONCLUSIONS: To achieve the policy goals of more access to KTx, sufficient funding is needed to support the increase in volume of pretransplant services. Future studies should assess the relative value of each service and explore ways to enhance efficiency.

Validation of a Core Patient-Reported Outcome Measure for Life Participation in Kidney Transplant Recipients: the SONG Life Participation Instrument.

Introduction: Life participation has been established as a critically important core for trials in kidney transplantation. We aimed to validate a patient-reported outcome measure for life participation in kidney transplant recipients. Methods: A psychometric evaluation of the Standardized Outcomes in Nephrology life participation (SONG-LP) measure was conducted in adult kidney transplant recipients. The measure includes 4 items of life participation (leisure, family, work, and social) each with a 5-point Likert scale. Each item is scored from 0 (never) to 4 (always) and the summary measure score the average of each item. Results: A total of 249 adult kidney transplant recipients from 20 countries participated. The SONG-LP instrument demonstrated internal consistency (Cronbach's α = 0.87; 95% confidence intervals [CI]: 0.83-0.90, baseline) and test-retest reliability over 1 week (intraclass correlation coefficient of 0.62; 95% CI: 0.54-0.70). There was moderate to high correlation (0.65; 95% CI: 0.57-0.72) with the PROMIS Ability to Participate in Social Roles and Activities Short Form 8a that assessed a similar construct, and moderate correlation with measures that assessed related concepts (i.e., EQ5D 0.57; 95% CI: 0.49-0.65), PROMIS Cognitive Functional Abilities Subset Short Form 4a (0.40; 95% CI: 0.29-0.50). Conclusion: The SONG-LP instrument is a simple, internally consistent, reliable measure for kidney transplant recipients and correlates with similar measures. Routine incorporation in clinical trials will ensure consistent and appropriate assessment of life participation for informed patient-centered decision-making.

Deceased Donor Kidney Transplantation for Older Transplant Candidates: A New Microsimulation Model for Determining Risks and Benefits.

BACKGROUND: Under the current US kidney allocation system, older candidates receive a disproportionately small share of deceased donor kidneys despite a reserve of potentially usable kidneys that could shorten their wait times. To consider potential health gains from increasing access to kidneys for these candidates, we developed and calibrated a microsimulation model of the transplantation process and long-term outcomes for older deceased donor kidney transplant candidates. METHODS: We estimated risk equations for transplant outcomes using the Scientific Registry of Transplant Recipients (SRTR), which contains data on all US transplants (2010-2019). A microsimulation model combined these equations to account for competing events. We calibrated the model to key transplant outcomes and used acceptance sampling, retaining the best-fitting 100 parameter sets. We then examined life expectancy gains from allocating kidneys even of lower quality across patient subgroups defined by age and designated race/ethnicity. RESULTS: The best-fitting 100 parameter sets (among 4,000,000 sampled) enabled our model to closely match key transplant outcomes. The model demonstrated clear survival benefits for those who receive a deceased donor kidney, even a lower quality one, compared with remaining on the waitlist where there is a risk of removal. The expected gain in survival from receiving a lower quality donor kidney was consistent gains across age and race/ethnic subgroups. LIMITATIONS: Limited available data on socioeconomic factors. CONCLUSIONS: Our microsimulation model accurately replicates a range of key kidney transplant outcomes among older candidates and demonstrates that older candidates may derive substantial benefits from transplantation with lower quality kidneys. This model can be used to evaluate policies that have been proposed to address concerns that the current system disincentivizes deceased donor transplants for older patients. HIGHLIGHTS: The microsimulation model was consistent with the data after calibration and accurately simulated the transplantation process for older deceased donor kidney transplant candidates.There are clear survival benefits for older transplant candidates who receive deceased donor kidneys, even lower quality ones, compared with remaining on the waitlist.This model can be used to evaluate policies aimed at increasing transplantation among older candidates.

Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes.

Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear. Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI). Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes. Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant. Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant. Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P < .001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%). Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

Infection, Rejection, and the Connection.

Solid organ transplantation is a life-saving treatment for people with end-stage organ disease. Immune-mediated transplant rejection is a common complication that decreases allograft survival. Although immunosuppression is required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression that can further tip the balance toward rejection. BK virus and other infections can induce damage that resembles the clinical pathology of rejection, and this complicates accurate diagnosis. Moreover, T cells specific for viral infection can lead to rejection through heterologous immunity to donor antigen directly mediated by antiviral cells. Thus, viral infections and allograft rejection interact in multiple ways that are important to maintain immunologic homeostasis in solid organ transplant recipients. Better insight into this dynamic interplay will help promote long-term transplant survival.

Trends in Coronary Artery Disease Screening before Kidney Transplantation.

Background: Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. In this study we describe temporal trends in CAD screening before kidney transplant in the United States. Methods: Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis on the basis of whether the patient's comorbidity burden met guideline definitions of high risk for CAD. We examined temporal trends in nonurgent CAD tests within the year before transplant and the composite of death and nonfatal myocardial infarction in the 30 days after transplant. Results: Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one nonurgent CAD test in the 1 year before transplant. From 2000 to 2015, the transplant program waitlist volume had increased as transplant volume stayed constant, whereas patients in the later eras had a slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year before transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in patients who were high risk but remained constant in patients who were low risk after 2008. Death or nonfatal myocardial infarction within 30 days after transplant decreased from 3% in 2000 to 2% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout the examined time periods. Conclusions: CAD testing rates before kidney transplantation have remained constant from 2000 through 2015, despite widespread changes in cardiology guidelines and practice.

Trends in Cost Attributable to Kidney Transplantation Evaluation and Waiting List Management in the United States, 2012-2017.

Importance: While recent policy reforms aim to improve access to kidney transplantation for patients with end-stage kidney disease, the cost implications of kidney waiting list expansion are not well understood. The Organ Acquisition Cost Center (OACC) is the mechanism by which Medicare reimburses kidney transplantation programs, at cost, for costs attributable to kidney transplantation evaluation and waiting list management, but these costs have not been well described to date. Objectives: To describe temporal trends in mean OACC costs per kidney transplantation and to identify factors most associated with cost. Design, Setting, and Participants: This economic evaluation included all kidney transplantation waiting list candidates and recipients in the United States from 2012 to 2017. A population-based study of cost center reports was conducted using data from all Center of Medicare & Medicaid-certified transplantation hospitals. Data analysis was conducted from June to August 2021. Exposures: Year, local price index, transplantation and waiting list volume of transplantation program, and comorbidity burden. Main Outcomes and Measures: Mean OACC costs per kidney transplantation. Results: In 1335 hospital-years from 2012 through 2017, Medicare's share of OACC costs increased from $0.95 billion in 2012 to $1.32 billion in 2017 (3.7% of total Medicare End-Stage Renal Disease program expenditure). Median (IQR) OACC costs per transplantation increased from $81 000 ($66 000 to $103 000) in 2012 to $100 000 ($82 000 to $125 000) in 2017. Kidney organ procurement costs contributed to 36% of mean OACC costs per transplantation throughout the study period. During the study period, transplantation hospitals experienced increases in kidney waiting list volume, kidney waiting list active volume, kidney transplantation volume, and comorbidity burden. For a median-sized transplantation program, mean OACC costs per transplantation decreased with more transplants (-$3500 [95% CI, -$4300 to -$2700] per 10 transplants; P < .001) and increased with year ($4400 [95% CI, $3500 to $5300] per year; P < .001), local price index ($1900 [95% CI, $200 to $3700] per 10-point increase; P = .03), patients listed active on the waiting list ($3100 [95% CI, $1700 to $4600] per 100 patients; P < .001), and patients on the waiting list with high comorbidities ($1500 [9% CI, $600 to $2500] per 1% increase in proportion of waitlisted patients with the highest comorbidity score; P = .002). Conclusions and Relevance: In this study, OACC costs increased at 4% per year from 2012 to 2017 and were not solely attributable to the cost of organ procurement. Expanding the waiting list will likely contribute to further increases in the mean OACC costs per transplantation and substantially increase Medicare liability.

Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United States.

BACKGROUND AND OBJECTIVES: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial and ethnic disparities in pediatric kidney transplantation access and related outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study of children <18 years of age active on the kidney transplant list from 2008 to 2019 using the Scientific Registry of Transplant Recipients. Log-logistic accelerated failure time models were used to determine the time from first activation on the transplant list and the time on dialysis to deceased donor transplant, each with KAS era or race and ethnicity as the exposure of interest. We used logistic regression to assess odds of delayed graft function. Log-rank tests assessed time to graft loss within racial and ethnic groups across KAS eras. RESULTS: All children experienced longer wait times from activation to transplantation post-KAS. In univariable analysis, Black and Hispanic children and other children of color experienced longer times from activation to transplant compared with White children in both eras; this finding was largely attenuated after multivariable analysis (time ratio, 1.16; 95% confidence interval, 1.01 to 1.32; time ratio, 1.13; 95% confidence interval, 1.00 to 1.28; and time ratio, 1.17; 95% confidence interval, 0.96 to 1.41 post-KAS, respectively). Multivariable analysis also showed that racial and ethnic disparities in time from dialysis initiation to transplantation in the pre-KAS era were mitigated in the post-KAS era. There were no disparities in odds of delayed graft function. Black and Hispanic children experienced longer times with a functioning graft in the post-KAS era. CONCLUSIONS: No racial and ethnic disparities from activation to deceased donor transplantation were seen before or after implementation of the KAS in multivariable analysis, whereas time on dialysis to transplantation and odds of short-term graft loss improved in equity after the implementation of the KAS, without compromising disparities in delayed graft function. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_07_CJN06740521.mp3.

Functional Consequences of Memory Inflation after Solid Organ Transplantation.

CMV is a major infectious complication following solid organ transplantation. Reactivation of CMV leads to memory inflation, a process in which CD8 T cells expand over time. Memory inflation is associated with specific changes in T cell function, including increased oligoclonality, decreased cytokine production, and terminal differentiation. To address whether memory inflation during the first year after transplantation in human subjects alters T cell differentiation and function, we employed single-cell-matched TCRαß and targeted gene expression sequencing. Expanded T cell clones exhibited a terminally differentiated, immunosenescent, and polyfunctional phenotype whereas rare clones were less differentiated. Clonal expansion occurring between pre- and 3 mo posttransplant was accompanied by enhancement of polyfunctionality. In contrast, polyfunctionality and differentiation state were largely maintained between 3 and 12 mo posttransplant. Highly expanded clones had a higher degree of polyfunctionality than rare clones. Thus, CMV-responsive CD8 T cells differentiated during the pre- to posttransplant period then maintained their differentiation state and functional capacity despite posttransplant clonal expansion.

Immunosuppression Considerations for Older Kidney Transplant Recipients.

PURPOSE OF REVIEW: While kidney transplantation improves the long-term survival of the majority of patients with end-stage kidney disease (ESKD), age-related immune dysfunction and associated comorbidities make older transplant recipients more susceptible to complications related to immunosuppression. In this review, we discuss appropriate management of immunosuppressive agents in older adults to minimize adverse events, avoid acute rejection, and maximize patient and graft survival. RECENT FINDINGS: Physiological changes associated with senescence can impact drug metabolism and increase the risk of posttransplant infection and malignancy. Clinical trials assessing the safety and efficacy of immunosuppressive agents in older adults are lacking. Recent findings from U.S. transplant registry-based studies suggest that risk-adjusted death-censored graft failure is higher among older patients who received antimetabolite avoidance, mammalian target of rapamycin inhibitor (mTORi)-based, and cyclosporine-based regimens. Observational data suggest that risk-adjusted mortality may be increased in older patients who receive mTORi-based and cyclosporine-based regimens but lower in those managed with T-cell induction and maintenance steroid avoidance/withdrawal. SUMMARY: Tailored immunosuppression management to improve patient and graft survival in older transplant recipients is an important goal of personalized medicine. Lower intensity immunosuppression, such as steroid-sparing regimens, appear beneficial whereas mTORi- and cyclosporine-based maintenance are associated with greater potential for adverse effects. Prospective clinical trials to assess the safety and efficacy of immunosuppression agents in older recipients are urgently needed.

Karnofsky Performance Score-Failure to Thrive as a Frailty Proxy?

Among patients listed for kidney transplantation, the Karnofsky Performance Status (KPS) Scale has been used as a proxy for frailty and proposed as a predictor of long-term posttransplant outcomes. The KPS is required by the Organ Procurement and Transplantation Network for all transplants; however, the interrater reliability of KPS reporting in kidney transplant candidates has not been well investigated, and there is concern regarding limitations of using KPS that may influence transplant eligibility. METHODS: We performed an observational study using existing Scientific Registry of Transplant Recipients data from 2006 to 2020 to examine the variability, reliability, and trends in the KPS among patients on the kidney transplant waitlist. RESULTS: Our analysis included 8197 kidney transplant candidates with >1 KPS in a 3-mo period. We observed 2-7 scores per patient with an average score of 78.9 (SD = 12, 95% confidence interval, 78.8-79.1). We found substantial variability in KPS reporting, in which 27% of the patients had scores that varied widely with 20-80 points in difference. Interrater reliability in the 10-point scale was poor (30%). When using a condensed 4-category scale (disabled, requires assistance, capable of self-care, normal activity), 38% of patients experienced at least a 1-category shift in their score. CONCLUSIONS: The lack of reliability in KPS reporting raises concerns when applying the KPS as a proxy for frailty and a metric to be considered when evaluating candidacy for kidney transplantation.

Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates.

INTRODUCTION: Current screening algorithms for coronary artery disease (CAD) before kidney transplantation result in many tests but few interventions. OBJECTIVE: The aim of this study was to study the utility of 6-minute walk test (6MWT), an office-based test of cardiorespiratory fitness, for risk stratification in this setting. METHODS: We enrolled 360 patients who are near the top of the kidney transplant waitlist at our institution. All patients underwent CAD evaluation irrespective of 6MWT results. We examined the association between 6MWT and time to CAD-related events (defined as cardiac death, revascularization, nonfatal myocardial infarction, and removal from the waitlist for CAD), treating noncardiac death and waitlist removal for non-CAD reasons as competing events. RESULTS: The 6MWT-based approach designated approximately 45% of patients as "low risk," whereas a risk factor- or symptom-based approach designated 14 and 81% of patients as "low risk," respectively. The 6MWT-based approach was not significantly associated with CAD-related events within 1 year (subproportional hazard ratio [sHR] 1.00 [0.90-1.11] per 50 m) but was significantly associated with competing events (sHR 0.70 [0.66-0.75] per 50 m). In a companion analysis, removing waitlist status from consideration, 6MWT result was associated with the development of CAD-related events (sHR 0.92 [0.84-1.00] per 50 m). CONCLUSIONS: The 6MWT designates fewer patients as high risk and in need of further testing (compared to risk factor-based approaches), but its utility as a pure CAD risk stratification tool is modulated by the background waitlist removal rate. CAD screening before kidney transplant should be tailored according to a patient's actual chance of receiving a transplant.

The organ procurement costs of expanding deceased donor organ acceptance criteria: Evidence from a cost function model.

A potential solution to the deceased donor organ shortage is to expand donor acceptability criteria. The procurement cost implications of using nonstandard donors is unknown. Using 5 years of US organ procurement organization (OPO) data, we built a cost function model to make cost projections: the total cost was the dependent variable; production outputs, including the number of donors and organs procured, were the independent variables. In the model, procuring one kidney or procuring both kidneys from double/en bloc transplantation from a single-organ donor resulted in a marginal cost of $55 k (95% confidence interval [CI] $28 k, $99 k) per kidney, and procuring only the liver from a single-organ donor results in a marginal cost of $41 k (95% CI $12 k, $69 k) per liver. Procuring two kidneys for two candidates from a donor lowered the marginal cost to $36 k (95% CI $22 k, $66 k) per kidney, and procuring two kidneys and a liver lowers the marginal cost to $24 k (95% CI $17 k, $45 k) per organ. Economies of scale were observed, where high OPO volume was correlated with lower costs. Despite higher cost per organ than for standard donors, kidney transplantation from nonstandard donors remained cost-effective based on contemporary US data.

Association of physical function and performance with peak VO2 in elderly patients with end stage kidney disease.

BACKGROUND: Physical function is impaired in end stage renal disease (ESRD). Various instruments have been used to assess the functional capabilities and health status of patients with ESRD, but it is not known which has the best association with peak VO2. AIMS: To assess the association between functional measures in ESRD. METHODS: Thirty nine elderly ESRD patients were evaluated with commonly used functional, health status, and quality of life measures, including maximal cardiopulmonary exercise testing (CPET), 6-min walk (6MWT), sit-to-stand test (STS), Veterans Specific Activity Questionnaire (VSAQ), upper and lower body strength, pulmonary function tests, and body composition determined by dual X-ray absorptiometry. The association between performance on these functional tools, clinical variables, and exercise test responses was assessed, and a non-exercise test multivariate model was developed to predict peak VO2. RESULTS: Peak VO2 was modestly related to VSAQ score (r = 0.59, p < 0.01), indices of upper and lower body strength (r = 0.45, p < 0.01 for both), and FEV1 (r = 0.51, p < 0.01). Functional and quality of life questionnaires were generally poorly related to one another and to peak VO2. In a multivariate model, 6MWT performance, forced expiratory volume in 1 s (FEV1), and VSAQ score were the best predictors of peak VO2, yielding a multiple R = 0.82, accounting for 67% of the variance in peak VO2. CONCLUSION: Exercise capacity can be reasonably estimated using non-exercise test variables in patients with ESRD, including a symptom questionnaire (VSAQ), 6MWT and FEV1. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov identifier: NCT01990495. Registered Nov 21, 2013.

Sex Disparity in Deceased-Donor Kidney Transplant Access by Cause of Kidney Disease.

BACKGROUND AND OBJECTIVES: Women with kidney failure have lower access to kidney transplantation compared with men, but the magnitude of this disparity may not be uniform across all kidney diseases. We hypothesized that the attributed cause of kidney failure may modify the magnitude of the disparities in transplant access by sex. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study of adults who developed kidney failure between 2005 and 2017 according to the United States Renal Data System. We used adjusted Cox models to examine the association between sex and either access to waitlist registration or deceased-donor kidney transplantation, and tested for interaction between sex and the attributed cause of kidney failure using adjusted models. RESULTS: Among a total of 1,478,037 patients, 271,111 were registered on the waitlist and 89,574 underwent deceased-donor transplantation. The rate of waitlisting was 6.5 per 100 person-years in women and 8.3 per 100 person-years for men. In adjusted analysis, women had lower access to the waitlist (hazard ratio, 0.89; 95% confidence interval, 0.89 to 0.90) and to deceased-donor transplantation after waitlisting (hazard ratio, 0.96; 95% confidence interval, 0.94 to 0.98). However, there was an interaction between sex and attributed cause of kidney disease in adjusted models (P<0.001). Women with kidney failure due to type 2 diabetes had 27% lower access to the kidney transplant waitlist (hazard ratio, 0.73; 95% confidence interval, 0.72 to 0.74) and 11% lower access to deceased-donor transplantation after waitlisting compared with men (hazard ratio, 0.89; 95% confidence interval, 0.86 to 0.92). In contrast, sex disparities in access to either the waitlist or transplantation were not observed in kidney failure secondary to cystic disease. CONCLUSIONS: The disparity in transplant access by sex is not consistent across all causes of kidney failure. Lower deceased-donor transplantation rates in women compared with men are especially notable among patients with kidney failure attributed to diabetes.

And Then There Were Three: Effects of Pretransplant Dialysis on Multiorgan Transplantation.

BACKGROUND: Simultaneous liver-kidney (SLK) and simultaneous heart-kidney (SHK) transplantation currently utilize 6% of deceased donor kidneys in the United States. To what extent residual kidney function accounts for apparent kidney allograft survival is unknown. METHODS: We examined all adult SLK and SHK transplants in the United States during 1995-2014. We considered the duration of dialysis preceding SLK or SHK (≥90 d, 1-89 d, or none) as a proxy of residual kidney function. We used multinomial logistic regression to estimate the difference in the adjusted likelihood of 6- and 12-month apparent kidney allograft failure between the no dialysis versus ≥90 days dialysis groups. RESULTS: Of 4875 SLK and 848 SHK recipients, 1775 (36%) SLK and 449 (53%) SHK recipients received no dialysis before transplant. The likelihood of apparent kidney allograft failure was 1%-3% lower at 12 months in SLK and SHK recipients who did not require pretransplant dialysis relative to recipients who required ≥90 days of pretransplant dialysis. Among 3978 SLK recipients who survived to 1 year, no pretransplant dialysis was associated with a lower risk of apparent kidney allograft failure over a median follow-up of 5.7 years (adjusted hazard ratio 0.73 [0.55-0.96]). CONCLUSIONS: Patients with residual kidney function at the time of multiorgan transplantation are less likely to have apparent failure of the kidney allograft. Whether residual kidney function facilitates function of the allograft or whether some SLK and SHK recipients have 3 functional kidneys is unknown. Sustained kidney function after SLK and SHK transplants does not necessarily indicate successful MOT.

Coronary Computed Tomography Angiography in Diagnosing Obstructive Coronary Artery Disease in Patients with Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Coronary computed tomography angiography (CCTA) is emerging as an important noninvasive testing modality for coronary angiography. The performance characteristic of CCTA in patients with advanced kidney disease is unknown. METHODS: We performed a systematic review and meta-analysis of studies specifically investigating the sensitivity and specificity of CCTA compared to coronary angiogram as a reference standard in patients with advanced kidney disease, defined as dialysis dependence or nearing kidney transplantation. Two independent investigators assessed studies for inclusion/exclusion, quality, and characteristics, while a third investigator adjudicated. RESULTS: We identified 4 studies including a total of 217 patients, of whom 159 were dialysis dependent. Three of the 4 studies had a high risk of bias in patient selection and study flow, while 1 study rated low in all areas of bias. The studies were heterogeneous in their patient selection and CCTA protocol but consistent in their definition of obstructive coronary artery disease. The pooled sensitivity and specificity for CCTA were 0.96 (0.87-0.99) and 0.66 (0.57-0.74), respectively. When we restricted the analysis to dialysis-dependent patients, the pooled sensitivity and specificity for CCTA were 0.99 (0.74-1.00) and 0.67 (0.49-0.82), respectively. CONCLUSIONS: Based on limited data, CCTA appears to have comparable sensitivity but lower specificity relative to the non-kidney disease population.

Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates.

Frailty is associated with adverse kidney transplant outcomes and can be assessed by subjective and objective metrics. There is increasing recognition of the value of metrics obtainable remotely. We compared the self-reported SF-36 physical functioning subscale score (SF-36 PF) with in-person physical performance tests (6-min walk and sit-to-stand) in a prospective cohort of kidney transplant candidates. We assessed each metric's ability to predict time to the composite outcome of waitlist removal or death, censoring at transplant. We built time-dependent receiver operating characteristic curves and calculated the area under the curve [AUC(t)] at 1 year, using bootstrapping for internal validation. In 199 patients followed for a median of 346 days, 41 reached the composite endpoint. Lower SF-36 PF scores were associated with higher risk of waitlist removal/death, with every 10-point decrease corresponding to a 16% increase in risk. All models showed an AUC(t) of 0.83-0.84 that did not contract substantially after internal validation. Among kidney transplant candidates, SF-36 PF, obtainable remotely, can help to stratify the risk of waitlist removal or death, and may be used as a screening tool for poor physical functioning in ongoing candidate evaluation, particularly where travel, increasing patient volume, or other restrictions challenge in-person assessment.

Impact of Functional Status on Outcomes of Simultaneous Pancreas-kidney Transplantation: Risks and Opportunities for Patient Benefit.

BACKGROUND: The impact of functional status on survival among simultaneous pancreas-kidney transplant (SPKT) candidates and recipients is not well described. METHODS: We examined national Scientific Registry of Transplant Recipients (SRTR) data for patients listed for SPKT in the United States (2006-2019). Functional status was categorized by center-reported Karnofsky Performance Score (KPS). We used Cox regression to quantify associations of KPS at listing and transplant with subsequent patient survival, adjusted for baseline patient and transplant factors (adjusted hazard ratio, 95% LCLaHR95%UCL). We also explored time-dependent associations of SPKT with survival risk after listing compared with continued waiting in each functional status group. RESULTS: KPS distributions among candidates (N = 16 822) and recipients (N = 10 316), respectively, were normal (KPS 80-100), 62.0% and 57.8%; capable of self-care (KPS 70), 23.5% and 24.7%; requires assistance (KPS 50-60), 12.4% and 14.2%; and disabled (KPS 10-40), 2.1% and 3.3%. There was a graded increase in mortality after listing and after transplant with lower functional levels. Compared with normal functioning, mortality after SPKT rose progressively for patients capable of self-care (aHR, 1.001.181.41), requiring assistance (aHR, 1.061.311.60), and disabled (aHR, 1.101.552.19). In time-dependent regression, compared with waiting, SPKT was associated with 2-fold mortality risk within 30 days of transplant. However, beyond 30 days, SPKT was associated with reduced mortality, from 52% for disabled patients (aHR, 0.260.480.88) to 70% for patients with normal functioning (aHR, 0.260.300.34). CONCLUSIONS: While lower functional status is associated with increased mortality risk among SPKT candidates and recipients, SPKT can provide long-term survival benefit across functional status levels in those selected for transplant.