Likelihood Of Transplantation Research Articles

Precision Lineage Deconvolution in Mixed Phenotype Acute Leukemia Using Cite-Seq Derived Hematopoietic Stages Identifies Lineage Dynamics Associated with Treatment Response

Introduction: Mixed phenotype Acute Leukemia (MPAL) is challenging due to ambiguous biology and lack of formal therapeutic guidelines. Although MPAL itself is rare, mixed phenotype lineage expression in secondary AML (sAML-MP) occurs with greater frequency and is associated with poor clinical outcomes. Multimodal single cell sequencing with cellular indexing of transcriptomes and epitopes (CITE-seq) offers more precise lineage characterization and assessment of lineage dynamics. Here we demonstrate a novel, unbiased approach to quantitative multistage hematopoietic lineage assessment in MPAL and sAML-MP using CITE-seq data. In addition, we demonstrate that this approach can be translated from single cell to bulk analysis. Methods: Sample preparation: Four MPAL and 6 sAML-MP samples displaying T-cell and myeloid subsets were identified and flow sorted into T and myeloid subgroups. RNA-seq was performed on each subset and analyzed using DESeq2. ComBat was used for batch correction when integrating with disparate data sources. Single cell lineage deconvolution: CITE-seq samples were processed using Seurat. A single cell deconvolution library was constructed using previously published hematopoietic stage clustering and labeling, and applied to CITE-seq data from five MPAL samples in the same dataset. Deconvolution algorithm parameters were optimized through a bootstrapping approach on in-silico sample mixtures. Bulk and translated lineage deconvolution: Bulk lineage deconvolution was performed using a published library of 13 stages of hematopoiesis derived from healthy donors.This was applied to bulk RNA-seq data from a cohort of published MPAL samples as well as the 6 sAML-MP and 4 MPAL samples described above. A pseudobulk was created for each CITE-seq lineage stage. Bulk lineage deconvolution was then re-run on the MPAL and sAML-MP samples using this library. Clinical Outcomes: A Wilcoxon signed-rank test was used to analyze differences among deconvolution-derived patient clusters, including response to induction therapy, specific gene mutations, and likelihood of transplant. Results: Lineage evolution with treatment: Deconvolution was applied on 17,848 MPAL cells and 35,038 control PBMC/BMMC cells. Antibody Derived Tag (ADT) features were consistent with lineage deconvolution stage assignments. CD38 was negatively correlated with HSC (-0.34, p < 0.001) and LMPP (-0.18, p < 0.001) while CD34 was positively correlated with both HSC (0.11, p < 0.001) and LMPP (0.27, p < 0.001) stages. MPAL 5 in particular was assessed at diagnosis and at two later time points. Unsupervised hierarchical clustering of all timepoints resulted in 10 clusters ( Figure A). The diagnostic time point was largely contained in clusters 4 (LMPP character, N = 1545 cells, 37.13%) and 9 (HSC character, N = 756 cells, 18.16%). The majority of both relapse timepoints were within cluster 4, with 76.77% (N=357 cells) of T1 and 73.92% (N=1100 cells) of T2 located in it. Bulk Unsupervised Analysis: Unsupervised analysis of sorted MPAL (N = 8), sorted AML-MP (N = 12), and unsorted MPAL (N = 24) bulk samples resulted in six distinct clusters, each with a distinct lineage signature ( Figure B). Some were enriched for more differentiated stages such as monocyte or GMP (clusters 6, 5), while others were enriched earlier stages such as LMPP (cluster 2). Secondary AML-MP samples were notably enriched in cluster 4. We found significant associations between lineage clusters and mutations in RUNX1 (p < 0.01), FLT3 (p = 0.004). Clinical Outcomes: Bulk RNA deconvolution cluster was significantly associated with complete remission (p = 0.0009). On average, individuals with an incomplete/no response to induction chemotherapy had a higher NK signature (p = 0.001), while individuals assigned to transplant had decreased LMPP character (p = 0.0495). Among the single-cell stages, decreased CLP 2 levels were associated with a poor response (p = 0.0224) while CMP / LMPP (p = 0.040) and CD4 N2 (p = 0.022) levels were decreased in patients who were able to undergo HSCT. Conclusions: Precise identification of lineage signatures in mixed phenotype leukemias shows promise in identifying clinically meaningful biological subsets of these diseases. Prospective analysis of lineage-derived biomarkers should be performed to undertake identification of formal risk stratification and treatment schemas.

Associations of longitudinal height and weight with clinical outcomes in pediatric kidney replacement therapy: results from the ESPN/ERA Registry

BackgroundAssociations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT.MethodsWe included patients < 20 years starting KRT in 33 European countries from 1995–2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) < –1.88 and tall stature as height SDS > 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates.ResultsWe included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78–0.86), tall (aHR: 0.65, 95% CI: 0.56–0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71–0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92–2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38–2.23) and obese (aHR: 1.49, 95% CI: 1.11–1.99) patients showed higher all-cause mortality risk than normal weight subjects.ConclusionsShort and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

312.5: Normothermic Machine Perfusion (NMP) Improves Access To Transplantation for Late Liver Re-Transplant Candidates

Introduction: Late liver re-transplantation (LLrT) is a complex surgical procedure. Candidates for LLrT spend longer on the waitlist than primary transplant candidates due to selectivity in accepting organ offers. A service design using NMP was implemented in October 2018 at a single centre to facilitate increased organ utilisation of marginal organs for high-risk recipients. The aim of this study was to assess if this intervention improved access to transplantation. Methods: Adult patients electively listed between 2015 and 2020 for LLrT were identified from the national transplant authority database. Transplant rates prior to (period 1) and after (period 2) local implementation of the NMP service design (October 2018) were compared at the study centre and compared to the collective data from other UK centres. A cause-specific Cox regression model was used, with the period modelled as a time-dependent covariate, and the period*centre interaction being the primary factor of interest. The model was corrected for UKELD, age, indication, and blood type. Post-transplant graft survival was assessed with univariable cox regression. Results: A total of 144 and 338 LLrT candidates were listed in the study and control centres respectively. At the study centre, the likelihood of transplantation within one year of listing increased from 56% to 68%, whilst a reduction in the LLrT rate was observed at other centres (Figure). Multivariable analysis, showed improved transplant access at the study centre in period 2 (period*centre interaction: HR: 1.83, 95%CI: 1.15-2.9, p=0.01). Post-transplant graft survival was not affected by the intervention (HR: 1.06, 95%CI: 0.41-2.69, p=0.903). Discussion: Implementation of the NMP service design significantly improved access to transplantation for LLrT candidates, without compromising graft survival. While organ utilisation benefit for NMP has been demonstrated before, this is a first study showing a direct patient benefit of NMP for patients with long expected waiting times.

Evolving Metrics of Quality for Kidney Transplant Candidates: Transplant Center Variability in Delisting and 1-Year Mortality.

Management of patients on the kidney transplant waitlist lacks oversight, and transplant centers can delist candidates without consequence. To better understand between-center differences in waitlist management, we examined delisting rates and mortality after delisting within 3 years of removal from the kidney transplant waitlist. This is a retrospective cohort study using data from the Scientific Registry of Transplant Recipients of adults listed for deceased donor kidney transplant in 2015 and followed until the end of 2018. Patients of interest were those delisted for reasons other than transplant, death, or transfer. Centers were excluded if they had fewer than 20 waitlisted patients per year. We calculated probability of delisting and death after delisting using multivariable competing risk models. During follow-up, 14.2% of patients were delisted. The median probability of delisting within 3 years, adjusted for center-level variability, was 7.0% (interquartile range [IQR]: 3.9% to 10.6%). Median probability of death was 58.2% (IQR: 40% to 73.4%). There was no meaningful correlation between probability of delisting and death (τ = -0.05, p = 0.34). There is significant variability in the rate of death after delisting across kidney transplant centers. Likelihood of transplant is extremely important to candidates, and improved data collection efforts are needed to inform whether current delisting practices are successfully removing patients who could not meaningfully benefit from transplant, or whether certain populations may benefit from remaining on the list and maintaining eligibility.

The Lung Allocation Score Remains Inequitable for Patients with PAH, Even After the 2015 Revision

<h3>Purpose</h3> The 2015 LAS revision intended to improve waitlist mortality and transplant rate for patients with pulmonary arterial hypertension (PAH). We sought to determine if the revision achieved its goals. <h3>Methods</h3> Using the OPTN STAR file, we analyzed the 15,807 registrants in the 3-year period before and after the revision. Registrants were divided into the LAS diagnostic categories: Group A-COPD; Group B-PAH; Group C-CF; & Group D-IPF. Competing risk regressions assessed the mutually exclusive competing risks of waitlist death and transplantation. Models were adjusted for age, gender, race, height, transplant type, and blood type. Cumulative incidence plots were created to visually inspect risks. <h3>Results</h3> Amongst the combined cohort, risk of waitlist death was lower post revision (sHR: 0.84, 95%CI: 0.78, 0.91), and likelihood of transplant was higher (sHR: 1.16, 95%CI: 1.12, 1.21). When stratified by LAS Category, risk of waitlist death remained similar for all diagnoses post revision, except in PAH, where risk of waitlist death improved (sHR: 0.57, 95%CI: 0.50, 0.85). Likelihood of transplant improved for all diagnoses post revision (all p<0.001). Prior to the revision, registrants with PAH had the highest risk of waitlist death and lowest likelihood of transplant (Figure). After the 2015 revision, registrants with PAH continued to have the highest risk of death, similar to those with IPF, who had the highest rate of transplant (sHR for IPF relative to PAH: 0.95, 95%CI: 0.67, 1.33). Registrants with PAH also continued to have the lowest rate of transplant, and registrants with COPD, which had the lowest risk of waitlist death, still tended to be transplanted at a higher rate than those with PAH (sHR for COPD relative to PAH 1.14, 95%CI: 0.99, 1.31). <h3>Conclusion</h3> Despite improving access to transplantation and risk of waitlist death for patients with PAH, the 2015 LAS revision did not go far enough, as patients with PAH still have the highest rate of waitlist death and lowest rate of transplant.

Outcomes of Frail Patients While Waiting for Kidney Transplantation: Differences between Physical Frailty Phenotype and FRAIL Scale.

Frailty is associated with poorer outcomes among patients waiting for kidney transplantation (KT). Several different tools to measure frailty have been used; however, their predictive value is unknown. This is a prospective longitudinal study of 449 KT candidates evaluated for frailty by the Physical Frailty Phenotype (PFP) and the FRAIL scale. During the study period, 296 patients received a KT, while 153 remained listed. Patients who did not get receive a transplant were more frequently frail according to PFP (16.3 vs. 7.4%, p = 0.013). Robust patients had fewer hospital admissions during the 1st year after listing (20.8% if PFP = 0 vs. 43.4% if ≥1, and 27.1% if FRAIL = 0 vs. 48.9% if ≥1) and fewer cardiovascular events (than FRAIL ≥ 1) or major infectious events (than PFP ≥ 1). According to PFP, scoring 1 point had an impact on patient survival and chance of transplantation in the univariate analysis. The multivariable analysis corroborated the result, as candidates with PFP ≥ 3 had less likelihood of transplantation (HR 0.45 [0.26–0.77]). The FRAIL scale did not associate with any of these outcomes. In KT candidates, pre-frailty and frailty according to both the PFP and the FRAIL scale were associated with poorer results while listed. The PFP detected that frail patients were less likely to receive a KT, while the FRAIL scale did not.

A machine learning prediction model for waiting time to kidney transplant.

Predicting waiting time for a deceased donor kidney transplant can help patients and clinicians to discuss management and contribute to a more efficient use of resources. This study aimed at developing a predictor model to estimate time on a kidney transplant waiting list using a machine learning approach. A retrospective cohort study including data of patients registered, between January 1, 2000 and December 31, 2017, in the waiting list of São Paulo State Organ Allocation System (SP-OAS) /Brazil. Data were randomly divided into two groups: 75% for training and 25% for testing. A Cox regression model was fitted with deceased donor transplant as the outcome. Sensitivity analyses were performed using different Cox models. Cox hazard ratios were used to develop the risk-prediction equations. Of 54,055 records retrieved, 48,153 registries were included in the final analysis. During the study period, approximately 1/3 of the patients were transplanted with a deceased donor. The major characteristics associated with changes in the likelihood of transplantation were age, subregion, cPRA, and frequency of HLA-DR, -B and -A. The model developed was able to predict waiting time with good agreement in internal validation (c-index = 0.70). The kidney transplant waiting time calculator developed shows good predictive performance and provides information that may be valuable in assisting candidates and their providers. Moreover, it can significantly improve the use of economic resources and the management of patient care before transplant.

P1660ACCESS TO KIDNEY TRANSPLANTATION IN THE UK CHINESE POPULATION: A UK RENAL REGISTRY ANALYSIS

Abstract Background and Aims Previous UK Renal Registry (UKRR) analyses and the Access to Transplantation and Transplant Outcome Measures (ATTOM) study have shown ethnic disparity in access to kidney transplants in the UK, but access to transplantation for the UK Chinese population has not been investigated In this UKRR analysis, we compared the likelihood of kidney transplantation between the UK White and UK Chinese renal populations, aiming to investigate whether there was evidence of ethnic disparity in access to kidney transplantation for this specific ethnic group. Method Data on all adult patients &amp;gt;=18 years who started renal replacement therapy (RRT) between 1/1/97 and 31/12/16 were extracted from the UKRR. Patients with ethnicity recorded as anything other than “Chinese” or “White” were excluded from analysis. Patients with ethnicity data missing were also excluded. Patients aged &amp;gt;= 75 years at the start of RRT were excluded because of the high prevalence of comorbidity which decreases the likelihood of transplantation and the very small proportion of patients receiving a kidney transplant in the UK in this age group. Socioeconomic status (SES) was measured using country-specific Index of Multiple Deprivation (IMD) quintiles derived from patient postcodes (1= most deprived, 5= least deprived). The independent variable of interest was Chinese ethnicity (Chinese vs White). Multivariable logistic regression models were used to investigate the relationship between Chinese ethnicity and being listed on the deceased donor transplant waiting list i) at start of RRT ii) 2 years after start of RRT iii) pre-emptive kidney transplantation, iv) kidney transplantation at 3 years after start of RRT, and v) living-donor kidney transplantation. The models were run unadjusted and then adjusted for the confounders, specified a priori, age, sex, primary renal disease and SES. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using robust standard errors to account for clustering by renal centre. Results The dataset comprised of 92,857 incident RRT patients. 0.5% (n=501) were of Chinese ethnicity, 76% (n=70,575) were White. The findings of the multivariable logistic regression analyses are presented in Table 1. Even after adjustment for potential confounders UK Chinese patients had lower odds of being waitlisted at the start of RRT (OR 0.71, [95% CI 0.54-0.94]) but were more likely to be waitlisted at 2 years (OR 1.28, [95% CI 1.02-1.61]) compared to White patients. UK Chinese individuals were also less likely to receive a pre-emptive kidney transplant (OR 0.47, [95% CI 0.29-0.78]), less likely to be transplanted within 3 years of starting RRT (OR 0.69, [95% CI 0.52-0.92]) or have a living-donor kidney transplant(LDKT) (OR 0.39, [95% CI 0.26-0.59]) compared to White patients. Conclusion This is the first study that has shown that UK Chinese renal patients are less likely to have the opportunity to receive a living or deceased kidney transplant. Future research needs to test whether later presentation or more rapid progression of renal disease could explain these observations. The higher odds of transplant listing at 2 years suggests fitness for transplantation is not a significant barrier. The reasons why this ethnic group are less likely to receive a LDKT is also not well understood. Understanding whether these disparities reflect modifiable policy, health system or donor/recipient level barriers will help ensure equitable access to transplantation.

The Transplant Index: A Novel Method to Predict Adult Liver Transplant Waitlist Outcomes.

The field of transplantation is shifting outcome priorities from 1-year survival to more comprehensive metrics including transplant rate and waitlist mortality. Identifying disenfranchised candidates (high waitlist death risk, low transplantation chance) can be a focus to improve outcomes. Given the waitlist outcomes (continued waiting, death, and transplantation), we aimed to identify factors predicting the likelihood candidates would undergo transplant or death by performing multivariate competing risk analyses of 121 198 candidates in the United Network for Organ Sharing database. We incorporated these probabilities (likelihood of transplantation and waitlist death) into the Transplant Index (TI) to identify disenfranchised candidates (high likelihood of death, low likelihood of transplantation). Half of the patients had low incidences of death and transplantation within 90 days (TI-inactive). The remaining were stratified into 10 groups within a predictive index, the TI. Low TI groups (TI 10, 20, 30) had 90-day transplant rates of 50.8%, 41.6%, and 39.8% respectively, and their respective 90-day death rates were 22.8%, 15.1%, and 10.9%. High TI groups (TI 80, 90, >90) had 90-day transplantation rates of 53.7%, 64.3%, and 73.9%, respectively, and 90-day death rates of 5.9%, 6.5%, and 6.7% respectively. As TI increased, the likelihood of transplantation increased and that of death decreased. Low-TI groups represent the disenfranchised candidates. The TI identifies disenfranchised candidates on the adult liver transplant waitlist. This is the subgroup that would benefit the most from efforts to increase access to transplantation.

Implantable cardioverter-defibrillators and survival in advanced heart failure patients with continuous-flow left ventricular assist devices: a systematic review and meta-analysis.

Implantable cardioverter-defibrillators (ICDs) implantation in heart failure (HF) patients with reduced ejection fraction improves survival by reducing mortality secondary to arrhythmic events. Whether advanced HF patients treated with continuous-flow left ventricular assist devices (CF-LVADs) derive similar benefit is controversial. We searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and Scopus from inception through November 2018 for studies examining the association between ICD implantation and all-cause mortality in patients with advanced HF and CF-LVADs. Analyses were performed using a random-effects model. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Heterogeneity and publication bias were formally assessed, using I2 and funnel plots, respectively. Eight observational studies with a total of 6416 patients (ICD group = 3450, no ICD group = 2966) met inclusion criteria. The majority of patients (84.6%) came from the two largest observational studies. There was no difference in mortality in the ICD and no ICD groups (HR 0.96, 95% CI 0.73-1.27, P = 0.79, I2 = 42%), and ICD implantation post-CF-LVAD was not associated with an improvement in mortality (HR 0.87, 95% CI 0.48-1.57, P = 0.64, I2 = 0%). Additionally, there was no significant difference in the likelihood of transplantation (HR 1.10, 95% CI 0.93-1.30, P = 0.28, I2 = 26%) or non-mortality adverse events between the two groups. Implantable cardioverter-defibrillator use was not associated with improved survival in advanced HF patients with CF-LVADs. These findings underscore the need to formally study the efficacy of ICDs in this population in a dedicated randomized controlled study.

Does the Canadian allocation system for highly sensitized patients work?

The number of sensitized heart transplant candidates is rising. Highly sensitized patients are disadvantaged because they encounter longer waiting times to heart transplant. Strategies to reduce their waiting times include waitlist prioritization and desensitization therapies. The purpose of this review is to describe the listing category for highly sensitized patients in the Canadian allocation system, examine the advantages and limitations of this strategy and provide an approach to the management of the highly sensitized patient awaiting heart transplant. Analysis of data from the United Network of Organ Sharing shows that the incidence of death or removal from the waitlist in patients listed for heart transplant increases as the calculated panel reactive antibody (cPRA) increases and is independent of medical urgency. In the Canadian allocation system, patients with cPRA more than 80% have a similar incidence of death on the waitlist as less sensitized patients, suggesting they survive to be transplanted. Furthermore, prioritizing and transplanting highly sensitized patients has been associated with acceptable post-transplant outcomes. The Canadian allocation system prioritizes highly sensitized patients to increase equity and access to transplantation while maintaining good post-transplant outcomes. Not all highly sensitized patients can wait for an organ, even if prioritized. A pragmatic individualized approach would consider the medical stability of the patient, the likelihood of transplant with a negative crossmatch and then determine whether waitlist prioritization or desensitization is the more appropriate strategy.

Regional Variation in Donor Refusal Rates Correlates with Poor Wait List Outcomes

Purpose Geographic variation in donation rates, transplant rates, and post-transplant outcomes in solid organ transplantation is well-described. We sought to test the hypothesis that organ refusal rates vary across regions and are associated with worse survival. Methods Retrospective review of the UNOS dataset (including the potential transplant recipients list which lists all offers of organs ultimately accepted for transplant) identified 5,639 pediatric ( heart transplant 2007-2017. Patients were stratified based on the UNOS region of listing. There were 12,447 donor hearts ( Results Regional refusal rates varied:73.5% to 93.1% (Table). Higher rates correlated with a lower likelihood of transplantation (r=0.60, p=0.048), higher waitlist mortality (r=0.67,p=0.008), a higher incidence of delisting for death or deterioration (r=0.61, p=0.04), higher mortality within 1 year of listing independent of transplant (r=0.080, p=0.003; see Figure), and higher 1 year post-transplant mortality (r=0.82, 0.002). Regional refusal rates were not correlated with mean regional wait times, or the number of donors available for each listed candidate. Conclusion Donor refusals rates vary widely between UNOS regions. Regions with high refusal rates also have poor outcomes following listing and transplantation.

Cost-effectiveness of liver transplantation in patients with colorectal metastases confined to the liver.

Patients with non-resectable colorectal metastases are currently treated with chemotherapy. However, liver transplantation can increase the 5-year survival rate from 9 to 56 per cent if the cancer is confined to the liver. The aim of this study was to estimate the cost-effectiveness of liver transplantation for colorectal liver metastases. A Markov model with a lifetime perspective was developed to estimate the life-years, quality-adjusted life-years (QALYs), direct healthcare costs and cost-effectiveness for patients with non-resectable colorectal liver metastases who received liver transplantation or chemotherapy alone. In non-selected cohorts, liver transplantation increased patients' life expectancy by 3·12 life-years (2·47 QALYs), at an additional cost of €209 143, giving an incremental cost-effectiveness ratio (ICER) of €67 140 per life-year (€84 667 per QALY) gained. In selected cohorts (selection based on tumour diameter, time since primary cancer, carcinoembryonic antigen levels and response to chemotherapy), the effect of liver transplantation increased to 4·23 life-years (3·41 QALYs), at a higher additional cost (€230 282), and the ICER decreased to €54 467 per life-year (€67 509 per QALY) gained. Given a willingness to pay of €70 500, the likelihood of transplantation being cost-effective was 0·66 and 0·94 (0·23 and 0·67 QALYs) for non-selected and selected cohorts respectively. Liver transplantation was cost-effective but only for highly selected patients. This might be possible in countries with good access to grafts and low waiting list mortality.

Abstract MP10: Increasing Obesity Prevalence in the United States End-stage Renal Disease Population

Background: Obesity has become a national epidemic, and is associated with increased risk for comorbid diseases including end-stage renal disease (ESRD). Among ESRD patients, obesity may improve dialysis-survival but decreases likelihood of transplantation, and as such, obesity prevalence may directly impact growth of the incident dialysis population. Methods: Incident adult ESRD patients with complete body mass index (BMI, kg/m 2 ) data were identified from the United States Renal Data System from 01/01/1995-12/31/2010 (n=1,822,598). Data from the Behavioral Risk Factor Surveillance System of the Centers for Disease Control and Prevention (n=4,303,471) represented the US population when weighted. Trends in BMI and obesity classes I (BMI of 30-34.9), II (BMI of 35-39.9), and III (BMI ≥40) were examined by year of dialysis initiation. Trends in median BMI slope were compared between the ESRD and US populations using linear regression. Results: Median BMI of ESRD patients in 1995 was 24.2 as compared to 28.0 in 2010, a 15.7% increase, while the US population’s median BMI increased from 24.2 in 1995 to 25.6 in 2010, a 5.8% increase. Comparable trends were noted with respect to prevalence of obesity classes I, II, and III (Table). BMI increase among the ESRD population was significantly more rapid than among the US population (β: 0.15, 95% CI: 0.14-0.17, p&lt;0.001) (Figure). Conclusion: The median BMI of ESRD patients and prevalence of obesity among ESRD patients is increasing more rapidly than the US population. Given the increased dialysis-survival and decreased likelihood of transplantation associated with obesity, healthcare costs will likely increase, and thus, future research should be directed at examining medical expenditures.

Evaluation of Pretransplant Donor-Specific Alloantibodies With Different Crossmatch Techniques

Donor-recipient crossmatching for kidney transplantation is an obligatory step for the transplant work-up process. Attention is currently put on single bead assay (SBA) that enables virtual crossmatching. In contrast, methods developed for complement binding capacity are still not routinely established. We compared modified, cytolytic flow cytometry crossmatch (cFC-XM) with complement-dependent serological crossmatch (CDC-XM), SBA, and flow cytometry crossmatch (FC-XM) to verify whether newly developed techniques may be beneficial for transplant immunological matching. Also, the cutoff value for donor-specific alloantibodies levels currently used for virtual crossmatch was verified. Serum from 22 sensitized patients was crossmatched with surrogate donors by CDC-XM, FC-XM, and cFC-XM, while anti-HLA antibodies were measured by SBA. In all cases, virtual crossmatch was positive at 5000 mean fluorescence intensity cutoff. Among 22 tested sera with donor-specific alloantibodies above 5000 mean fluorescence intensity, the positive CDC-XM result was noted only in 41% of patients (n = 9), but positive FC-XM was noted in 86% (n = 19), and further lytic antibodies (cFC-XM) were confirmed in 27% of cases (n = 6). Our results suggest that donor-recipient immunological matching for kidney transplantation requires different methods to verify the importance of alloantibodies, and improvement in laboratory investigation is needed. This is especially important for immunized patients that have many types of alloantibodies and virtual crossmatching used as a tool for deceased donor allocation should balance between the likelihood of transplantation and risk of positive crossmatch result.

Implantable Cardioverter-Defibrillators in Patients With a Continuous-Flow Left Ventricular Assist Device: An Analysis of the INTERMACS Registry

ObjectivesThis study sought to determine if the presence of implantable cardioverter-defibrillators (ICD) provided a mortality benefit during continuous-flow left ventricular assist device (LVAD) support. BackgroundAn ICD decreases mortality in selected patients with advanced heart failure and have been associated with reduced mortality in patients with pulsatile LVAD. However, it is unclear whether that benefit extends to patients with a contemporary continuous-flow LVAD. MethodsPropensity score matching was used to generate a cohort of patients with similar baseline characteristics. The primary outcome was freedom from death during LVAD support. Secondary endpoints included freedom from unexpected death, likelihood of transplantation and recovery, and adverse events. ResultsAmong 16,384 eligible patients in the Interagency Registry for Mechanically Assisted Circulatory Support registry, 2,209 patients with an ICD and 2,209 patients without one had similar propensity scores and were included. The presence of an ICD was associated with an increased mortality risk (hazard ratio: 1.20; 95% confidence interval [CI]: 1.04 to 1.39; p = 0.013) and an increased risk of unexpected death during device support (HR: 1.33; 95% CI: 1.03 to 1.71; p = 0.03). Patients with an ICD were more likely to undergo transplantation (HR: 1.16; 95% CI: 0.99 to 1.35; p = 0.06) and less likely to have LVAD explant for recovery (HR: 0.53, 95% CI: 0.29 to 0.98; p = 0.04). Patients with an ICD had a higher rate of treated ventricular arrhythmias (rate ratio: 1.27; 95% CI: 1.10 to 1.48; p = 0.001) and rehospitalization (rate ratio: 1.08; 95% CI: 1.04 to 1.12; p < 0.0001), but rates of hemorrhagic stroke were similar (rate ratio: 1.01; 95% CI: 0.81 to 1.26; p = 0.98). ConclusionsAmong patients with a continuous flow LVAD, the presence of an ICD was not associated with reduced mortality.

Abstract 21394: Socioeconomic and Racial Disparities in Outcomes Among Patients Listed for Heart Transplant in the United States

Background: Socioeconomic and racial disparities in outcomes among patients with heart failure are well-documented. Whether such disparities exist among patients awaiting heart transplant (HT) is unclear. We aimed to characterize the associations of socioeconomic status (SES) and race with outcomes among patients listed for HT. Methods: Patients listed for heart transplant between 1994 and 2014 were included (n = 64,276). SES indicators included insurance status, education, and neighborhood SES (nSES), measured by zip code using a composite index. The primary outcome was a composite of death or delisting and the secondary outcome was transplant. Multivariate analyses were employed to adjust for race, SES, comorbidity, and clinical severity at time of listing. Results: Non-white race, low education, Medicare, Medicaid, and lower nSES (Figure 1) were associated with higher unadjusted risks of death or delisting. After adjustment, the associations with less than high school (HR=1.39) and college education (HR=0.93), Medicare (HR=1.22), Medicaid (HR=1.16), and lowest nSES quartile (HR=1.06) remained significant (p &lt; 0.05; Figure 2). Risks associated with black race and low nSES decreased significantly over time. Adjusted incidence of transplant was significantly lower among blacks (HR = 0.90), but higher among other non-white patients. Conclusions: Low SES is associated with poorer outcomes during HT listing, and there are racial disparities in the likelihood of transplant. Some of these disparities have narrowed over time. Further research is needed to identify the underlying cause of these disparities, which are not explained by measured clinical characteristics.

P010 Higher definition CPRA: What’s the (decimal) point?

Aim cPRA is an estimate of the percentage of donors excluded by a potential recipient’s unacceptable antigens and is typically expressed as an integer. For very highly sensitized patients, integer rounding may reduce how informative cPRA is for important metrics such as time to DSA negative offer. We analyzed the distribution and clinical impact of cPRA to decimal point based (cPRAd) in a highly sensitized Canadian kidney waitlist (cPRA>=95%). Methods All patients registered the Canadian Blood Services’ Highly Sensitized Patient (HSP) Program included in at least one allocation run ( n = 1025) from 10/18/13 to 08/04/16 were included and cPRAd calculated to 1 decimal place. Distribution of cPRAd, time to first DSA negative match or to end of study period and proportion of patients transplanted by cPRAd was determined. Result 52% of subjects had cPRAd>=99.8%. 515 patients received at least one DSA negative match during the study period (Fig. 1A). Time to match increased progressively across cPRAd, notable even between integer values (Fig. 1B). Median time to first match increases progressively above cPRAd 98% and particularly above 99.7%. (Fig. 1C). Noting not all matches results in offers/transplants, for those patients transplanted with cPRAd>=98%, proportion transplanted decreases across cPRAd 0.1% intervals (Fig. 2) (Linear relationship = −0.279 * (cPRAd) + 27.95, R 2 = 0.59, p = 0.00004). Conclusions cPRAd provides more informative time to match and likelihood of transplant, than rounded integer cPRA, which in turn may better inform patients, and augment application in allocation strategies. Download high-res image (458KB) Download full-size image

Variation in Access to Kidney Transplantation Across Renal Programs in Ontario, Canada.

In the United States, kidney transplant rates vary significantly across end-stage renal disease (ESRD) networks. We conducted a population-based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1-, 5-, and 10-year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for "healthy" dialysis patients (aged 18-50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow-up of 11 years). Among 23 022 chronic dialysis patients, the 10-year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8-10.7%) to 31.4% (95% CI 16.5-47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2-0.5) to 1.5 (95% CI 1.4-1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.

Infants Requiring Maintenance Dialysis: Outcomes of Hemodialysis and Peritoneal Dialysis

The impact of different dialysis modalities on clinical outcomes has not been explored in young infants with chronic kidney failure. Cohort study. Data were extracted from the ESPN/ERA-EDTA Registry. This analysis included 1,063 infants 12 months or younger who initiated dialysis therapy in 1991 to2013. Type of dialysis modality. Differences between infants treated with peritoneal dialysis (PD) or hemodialysis (HD) in patient survival, technique survival, and access to kidney transplantation were examined using Cox regression analysis while adjusting for age at dialysis therapy initiation, sex, underlying kidney disease, and country of residence. 917 infants initiated dialysis therapy on PD, and 146, on HD. Median age at dialysis therapy initiation was 4.5 (IQR, 0.7-7.9) months, and median body weight was 5.7 (IQR, 3.7-7.5) kg. Although the groups were homogeneous regarding age and sex, infants treated with PD more often had congenital anomalies of the kidney and urinary tract (CAKUT; 48% vs 27%), whereas those on HD therapy more frequently had metabolic disorders (12% vs 4%). Risk factors for death were younger age at dialysis therapy initiation (HR per each 1-month later initiation, 0.95; 95% CI, 0.90-0.97) and non-CAKUT cause of chronic kidney failure (HR, 1.49; 95% CI, 1.08-2.04). Mortality risk and likelihood of transplantation were equal in PD and HD patients, whereas HD patients had a higher risk for changing dialysis treatment (adjusted HR, 1.64; 95% CI, 1.17-2.31). Inability to control for unmeasured confounders not included in the Registry database and missing data (ie, comorbid conditions). Low statistical power because of relatively small number of participants. Despite a widespread preconception that HD should be reserved for cases in which PD is not feasible, in Europe, we found 1 in 8 infants in need of maintenance dialysis to be initiated on HD therapy. Patient characteristics at dialysis therapy initiation, prospective survival, and time to transplantation were very similar for infants initiated on PD or HD therapy.