US Kidney Research Articles

Early Effects of the End-Stage Renal Disease Treatment Choices Model on Kidney Transplant Waitlist Additions.

Despite the mortality benefit of kidney transplantation over dialysis, only 13% of patients with end-stage kidney disease are on the transplant waitlist. Given the low rates of transplant waitlisting in the US, Medicare launched the End-Stage Renal Disease Treatment Choices (ETC) Model in 2021, the largest mandatory trial of payment incentives in kidney disease, which randomized 30% of healthcare markets to financial bonuses/penalties to improve kidney transplantation and home dialysis use. This study examines the effect of ETC payment adjustments on US kidney transplant waitlist additions. Using data from the Organ Procurement and Transplantation Network registry, we examined kidney transplant waitlisting trends between 01/01/2017 and 06/30/2022. Participants were divided into intervention and control arms of the ETC Model. Using an interrupted time series design, we compared slope changes in waitlist additions post-ETC Model implementation (implementation date: 01/01/2021) between the two arms, while accounting for differential changes during the COVID-19 pandemic. Results were stratified by race and ethnicity (White, Black, Hispanic, and other). To examine balance between the two ETC arms, we conducted supplementary analyses using United States Renal Data System and Medicare data. Following implementation of the ETC Model, there were 5,550 waitlist additions in the intervention and 11,332 additions in the control arm (versus 14,023 and 30,610 additions before the ETC Model). Post-ETC, there were no significant differences in kidney transplant waitlist additions between the two arms for the overall cohort (slope difference 6.9 new listings/month, 95% CI: -7.4 to 21.1) or among either White (slope difference 2.6/month, 95% CI -3.0 to 8.1), Black (slope difference 2.2/month, 95% CI: -4.3 to 8.7), or Hispanic (slope difference 0.2/month, 95% CI: -4.5 to 4.9) patients. In the 18 months following implementation, the ETC Model was not associated with significant changes in new kidney transplant waitlist additions.

Decline in Opioid Prescriptions in US Dialysis and Kidney Transplant Patients, 2011-2020

Decline in Opioid Prescriptions in US Dialysis and Kidney Transplant Patients, 2011-2020

328.2: ABO-compatible US kidney allocation with ABO-adjusted CPRA.

328.2: ABO-compatible US kidney allocation with ABO-adjusted CPRA.

Disparities in Access to Timely Waitlisting Among Pediatric Kidney Transplant Candidates.

Kidney transplantation with minimal or no dialysis exposure provides optimal outcomes for children with end-stage kidney disease. We sought to understand disparities in timely access to transplant waitlisting. We conducted a retrospective, registry-based cohort study of candidates ages 3 to 17 added to the US kidney transplant waitlist 2015 to 2019. We defined "preemptive waitlisting" as waitlist addition before receiving dialysis and compared demographics of candidates based on preemptive status. We used competing risk regression to determine the association between preemptive waitlisting and transplantation. We then identified waitlist additions age >18 who initiated dialysis as children, thereby missing pediatric allocation prioritization, and evaluated the association between waitlisting with pediatric prioritization and transplantation. Among 4506 pediatric candidates, 48% were waitlisted preemptively. Female sex, Hispanic ethnicity, Black race, and public insurance were associated with lower adjusted relative risk of preemptive waitlisting. Preemptive listing was not associated with time from waitlist activation to transplantation (adjusted hazard ratio 0.94, 95% confidence interval 0.87-1.02). Among transplant recipients waitlisted preemptively, 68% had no pretransplant dialysis, whereas recipients listed nonpreemptively had median 1.6 years of dialysis at transplant. Among 415 candidates initiating dialysis as children but waitlisted as adults, transplant rate was lower versus nonpreemptive pediatric candidates after waitlist activation (adjusted hazard ratio 0.54, 95% confidence interval 0.44-0.66). Disparities in timely waitlisting are associated with differences in pretransplant dialysis exposure despite no difference in time to transplant after waitlist activation. Young adults who experience delays may miss pediatric prioritization, highlighting an area for policy intervention.

Graft Survival of En Bloc Deceased Donor Kidneys Transplants Compared With Single Kidney Transplants.

The US Kidney Allocation System allocates en bloc deceased donor kidney grafts from donors <18 kg in sequence A along with single kidney transplants (SKTs) from kidney donor profile index (KDPI) top 20% donors. Although en bloc grafts outperform SKT grafts holding donor weight constant, it is unclear if en bloc grafts from the smallest pediatric donors perform the same as top 20% KDPI SKTs. Using the Scientific Registry of Transplant Recipients, we compared the donor characteristics and graft survival of en bloc grafts from the smallest donors (<8 kg) and from larger donors (≥8 kg) with SKTs by KDPI sequence for transplants performed in 2021. Larger donor en blocs had similar 1-y survival to sequence A SKTs estimated by the Kaplan-Meier method (96% versus 96%, P = 0.9), but the smallest donor en blocs had significantly shorter 1-y survival than those SKTs (80% versus 96%, P < 0.01). Using transplants from 2010 to 2012, the smallest donor en blocs had similar 10-y survival to sequence A SKTs (69% versus 64%, P = 0.3). These findings suggest that future updates of the Kidney Allocation System should include a score specific to pediatric donors to account for these differences in en bloc graft survival.

Predictive value of donor kidney quality assessment and risk quantification scores on 5-year outcomes of deceased donor kidney transplantation.

Due to the excess demand for deceased donor kidneys, risk quantification scores were developed to help with kidney allocation. The kidney donor risk index (KDRI) is used in the US kidney allocation system. We currently use expanded criteria (UNOS) and Remuzzi scoring for allocation of deceased donor kidneys and the utility of KDRI in our cohort is unknown. We aim to evaluate the association of KDRI with relation to 5year graft and patient survival. Retrospective cohort study of 225 adults who received a deceased donor kidney transplant between 1 Nov 2005 and 30 June 2014. Patients were followed up for 5years or until graft-loss or death. Implant biopsies of donor kidneys were done and the Remuzzi score was calculated. The median age was 48 (IQR 42, 52.5) years and 50.7% were male. KDRI-USA, KDRI-THAI, and KDRI-AUST were found to have no correlation with 5year graft survival. Donor characteristics which define an expanded criteria donor kidney, not associated with 5year graft survival are age (p = 0.58), terminal creatinine (p = 0.71) and history of hypertension (p = 0.35). Donor cerebrovascular accident (CVA) as a cause of death (p = 0.02) and Remuzzi score were associated with graft survival at 5years, with 75.8% with Remuzzi score ≤ 3 vs 24.2% with Remuzzi score of > 3 achieving 5year graft survival (p = 0.001). The association of KDRI with graft and patient survival was not demonstrated in our cohort. Histological assessment of the transplant kidney remains the best method of predicting long-term survival during donor selection.

Association of Race and Ethnicity With High Longevity Deceased Donor Kidney Transplantation Under the US Kidney Allocation System

Rationale & ObjectiveThe US Kidney Allocation System (KAS) prioritizes candidates with ≤20% Estimated Post-Transplant Survival (EPTS) for high longevity kidneys defined by a ≤20% Kidney Donor Profile Index (KDPI). Use of EPTS in the KAS deprioritizes candidates with older age, diabetes, and longer dialysis durations. We assessed whether this use also disadvantages racial-ethnic minority candidates, who are younger but more likely to have diabetes and longer durations of kidney failure requiring dialysis. Study DesignObservational cohort study. Setting& Participants: Adult candidates for and recipients of kidney transplantation represented in the Scientific Registry of Transplant Recipients from January 2015 through December 2020. ExposureRace and ethnicity. OutcomesAge-adjusted assignment to ≤20% EPTS, transplantation of a ≤20% KDPI kidney, and post-transplant survival in longevity matched recipients by racial-ethnicity. Analytic ApproachMultivariable logistic regression, Fine-Gray competing risks survival analysis, and Kaplan-Meier and Cox Proportional Hazards methods. ResultsThe cohort included 199,444 candidates (7% Asian, 29% Black, 19% Hispanic/Latino, 43% White) listed for deceased donor kidney transplantation. Non-White candidates had significantly higher rates of diabetes, longer dialysis duration, and were younger than White candidates. Adjusted for age, Asian, Black, and Hispanic/Latino candidates had significantly lower odds of having a ETPS score ≤20% (OR 0.86, [0.81, 0.91], 0.52 [0.50, 0.54], and 0.49, [0.47, 0.51]), and were less likely to receive a ≤20% KDPI kidney (subHR 0.70 [0.66, 0.75], 0.89 [0.87, 0.92], and 0.73 [0.71, 0.76]), compared to White candidates. Among recipients with ≤20% EPTS scores transplanted with a ≤20% KDPI deceased donor kidney, Asian and Hispanic recipients had lower post-transplant mortality (HR 0.45 [0.27, 0.77], and 0.63 [0.47, 0.86]) and Black recipients had higher but not statistically significant post-transplant mortality (HR 1.22 [0.99, 1.52]) compared to White recipients. LimitationsProvider reported race-ethnicity data and 5-year post transplant follow-up period. ConclusionsThe US kidney allocation system is less likely to identify racial-ethnic minority candidates as having a ≤20% EPTS score which triggers allocation of high longevity deceased donor kidneys. These findings should inform the OPTN about how to remedy racial/ethnic disparities introduced through KAS’s current approach of allocating allografts with longer predicted longevity to recipients with longer estimated post-transplant survival.

Calibration of Priority Points for Sensitization Status of Kidney Transplant Candidates in the United States.

A primary change to the national organ allocation system in 2014 for deceased donor kidney offers was to weight candidate priority based on sensitization (i.e. calculated panel reactive antibody percentage [CPRA%]) using a sliding scale. Increased priority for sensitized patients could improve equity in access to transplantation for disadvantaged candidates. We sought to evaluate the effect of these weights using a contemporary cohort of adult US kidney transplant candidates. We used the national Scientific Registry of Transplant Recipients to evaluate factors associated with sensitization using multivariable logistic models and rates of deceased donor transplantation using cumulative incidence models accounting for competing risks and multivariable Cox models. We examined 270,912 adult candidates placed on the waiting list between Jan,2016-September,2023. Six-year cumulative incidence of deceased donor transplantation for candidates with cPRA%=[80-85) and [90-95) was 48% and 53% respectively, as compared to 37% for candidates with cPRA%=[0-20). In multivariable models, candidates with high cPRA% had the highest adjusted hazards for deceased donor transplantation. There was significant effect modification such that the association of high cPRA% with adjusted rates of deceased donor transplantation varied by region of the country, gender, race/ethnicity, prior dialysis time and blood type. Results indicate that the weighting algorithm for highly sensitized candidates may overinflate the need for prioritization and lead to higher rates of transplantation. Findings suggest re-calibration of priority weights for allocation is needed to facilitate overall equity in access to transplantation for prospective kidney transplant candidates. However, priority points should also account for subgroups of candidates who are disadvantaged for access to donor offers.

COVID-19 and Access to Kidney Transplantation for Older Candidates in the United States: A National Registry Study

Rationale & ObjectiveCOVID-19 has likely impacted accessibility to transplantation services among older adults (age ≥65). We quantified the impact of COVID-19 on kidney transplantation access for older kidney-only candidates registered on the US kidney waitlist. Study DesignRetrospective analysis of registry data Setting & Participants57,222 older adults who were part of or added to the US kidney waitlist between 1/1/2016-2/28/2022, identified using the Scientific Registry of Transplant Recipients (SRTR). ExposuresFour COVID-19 waves and one non-wave period based on the national incidence of COVID-19 in the United States (Initial: 3/15/20-5/31/20; winter 2020-21: 12/1/20-1/31/21; delta: 8/1/21-9/30; omicron: 12/1/21-2/28/22; non-wave: inter-wave periods) OutcomesWaitlist registrations, deceased-donor kidney transplants, living-donor kidney transplants, waitlist mortality, and waitlist removals due to deteriorating condition (hereafter referred to as removals) Analytical ApproachPoisson regression for the adjusted incidence rate ratio (aIRR) of each outcome during the COVID-19 waves and the non-wave period relative to reference [1/1/16-12/31/19], adjusted for seasonality and secular trends. ResultsWaitlist registrations initially declined, and increased henceforth. Deceased donor kidney transplants and living donor kidney transplants remained below expected during all waves. Waitlist mortality peaked during the winter 2020-21 wave (aIRR: 1.701.982.30) and has declined since; mortality rates were 139%, 107%, and 251% above expected for Black candidates, men, and candidates aged ≥75 years, respectively, during the winter 2020-21 wave. Removals increased from 22% below expected (initial wave) to 26% above expected (omicron wave); removals were non-significantly higher than expected during the omicron wave for older Black and Hispanic candidates. LimitationsThe findings are not generalizable to those listed at earlier ages with prolonged waitlist times. Additionally, using national COVID-19 incidence doesn’t consider local policy and healthcare variations. Lastly, aIRRs must be interpreted cautiously due to smaller daily event counts. ConclusionsCOVID-19 was associated with fewer transplants, and increased mortality and removals in older kidney transplant candidates. Transplant providers should consider this impact and implement policies and practices to ensure the continuity of care.

Defiance of Occam’s Razor: Recent Changes in US Kidney Allocation and Impact on Efficiency and Marginal Kidney Outcomes

Defiance of Occam’s Razor: Recent Changes in US Kidney Allocation and Impact on Efficiency and Marginal Kidney Outcomes

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

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

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

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. 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. 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. Limited available data on socioeconomic factors. 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. 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.

Glucose and cell confluency regulation of HDGF and beta-catenin nuclear localization

Introduction: Diabetes mellitus (DM) is the seventh leading cause of death in the US and diabetic kidney disease (DKD)is the cause of nearly 50% of individuals receiving dialysis. Kidney proximal tubule (PT) cells are sensitive to injury under diabetic conditions of high glucose. Maladaptive repair can cause fibrosis and loss of PT function contributing to end-stage renal disease. PT cell proliferation re-establishes the monolayer responsible for PT functionality. Preliminary lab findings showed increased abundance and nuclear localization of Hepatoma-derived growth factor (HDGF), known to regulate proliferation, in cells grown at low (&lt;40%) confluency in high glucose supplemented growth media. This change associated with altered nuclear co-localization with β-catenin (ß-Cat), involved in renal fibrosis, suggesting crosstalk between both factors may be involved in PT cell responses in DKD. Hypothesis: Cell confluency and glucose concentrations regulate the spatial and absolute abundance/degradation of HDGF altering cell signaling pathways in PT cells. Methods: Cultured human kidney PT cells (HK-11 cell line) were grown to low and high confluency under normal (5mM) and high (25mM) glucose conditions. RNA was collected via column purification for analysis of cell signaling. RNASeq and bioinformatic analysis. revealed transcript abundances and respective statistical significances between normal and high glucose conditions grown to low confluency. MetaCore and STRING were utilized to examine fold change differences of the transcriptome and affected pathways. To determine regulation of protein abundance, HK-11 cells were cultured in normal glucose media to 80-90% confluency and treated with no agent (control), DMSO, MG132 (proteasome inhibitor), and chloroquine (lysosome inhibitor), and abundance of HDGF and β-Cat activation analyzed by immunoblot. Results: HDGF transcripts from conditions of normal and high glucose grown to low confluency were found in relatively equal abundance (q ≤ 1). Pathway analyses revealed genes associated with multiple pathways including nuclear signaling, ER stress, proliferation and ubiquitination exhibited differential transcript abundance at statistically significant values. Immunoblot analysis suggested that HDGF is degraded via the lysosome. Conclusions: HDGF regulation by diabetes-like high glucose does not occur at the level of transcription and but through lysosomal degradation. ß-Cat nuclear localization is increased under conditions of high glucose and low cellular confluency. To confirm HDGF degradation and ß-Cat activation, more replicates are needed for statistical analysis. Future studies will determine the role of β-cat activation on HDGF abundance and nuclear localization. NIH T35-DK072923, P20-GM103436, NIH P20 GM113226, P50 AA024337, P30 ES030283 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The real unmet need: A multifactorial approach for identifying sensitized kidney candidates with low access to transplant.

At the start of 2020, the kidney waiting list consisted of 2526 candidates with a calculated panel reactive antibody (CPRA) of 99.9% or greater, a cohort demonstrated in published research to have meaningfully lower than average access to transplantation even under the revised kidney allocation system (KAS). This was a retrospective analysis of US kidney registrations using data from the OPTN [Reference (https://optn.transplant.hrsa.gov/data/about-data/)]. The period-prevalent study cohort consisted of US kidney-alone registrations who waited at least 1 day between April 1, 2016, when HLA DQ-Alpha and DP-Beta unacceptable antigen data became available in OPTN data collection, to December 31, 2019. Poisson rate regression was used to model deceased donor kidney transplant rates per active year waiting and using an offset term to account for differential at-risk periods. Median time to transplant was estimated for each IRR group using the Kaplan-Meier method. Sensitivity analyses were included to address geographic variation in supply-to-demand ratios and differences in dialysis time or waiting time. In this study, we found 1597 additional sensitized (CPRA 50-<99.9%) candidates with meaningfully lower than average access to transplant when simultaneously taking into account CPRA and other factors. In combination with CPRA, candidate blood type, Estimated Post-Transplant Survival Score (EPTS), and presence of other antibody specificities beyond those in the current, 5-locus CPRA were found to influence the likelihood of transplant. In total, this suggests approximately 4100 sensitized candidates are on the waiting list who represent a community of disadvantaged patients who may benefit from progressive therapies and interventions to facilitate incompatible transplantation. Though associated with higher risks, such interventions may nevertheless be more attractive than remaining on dialysis with the associated accumulation of mortality risk over time.

Reining in Costs of Kidney Dialysis: US Supreme Court Offers Hope to End Predatory Pricing

PurposeTwo for-profit dialysis providers control >70% of the US kidney dialysis market. They use their excessive market power to force private insurers to pay nearly 4 times the Medicare rate, earning exorbitant profits for themselves at the expense of the health care system. Both the legislative and judicial systems have been called on to address this inequity, so far without success. MethodsWe examined the history of this issue as set forth in official Centers for Medicare & Medicaid Services, US Department of Health and Human Services, Federal Trade Commission, and other regulatory documents as well as court filings and opinions. We analyzed the legislative efforts to address the problem and the judicial response. FindingsWe found that most efforts, to date, have failed. However, a 2022 US Supreme Court decision helps illuminate a path forward, in large part by defining the limits of judicial intervention. ImplicationsWe identify a path forward that would separate the monopolistic players using a multipronged effort involving US Department of Justice, Federal Trade Commission, Office of Inspector General, and states attorneys general. We also caution that, based on our research, the providers could challenge further efforts by deciding to withdraw services in certain areas or refuse to do business with certain insurers, resulting in patients having difficulty accessing dialysis.

A National Registry for People With All Stages of Kidney Disease: The National Kidney Foundation (NKF) Patient Network

The National Kidney Foundation (NKF) launched the first national US kidney disease patient registry, the NKF Patient Network, that is open to patients throughout the continuum of chronic kidney disease (CKD). The Network provides individualized education and will facilitate patient-centered research, clinical care, and health policy decisions. Here, we present the overall design and the results of a feasibility study that was conducted July through December2020. Longitudinal observational cohort study of patient-entered data with or without electronic health care record (EHR) linkage in collaboration with health systems. People with CKD, age≥18 years, are invited through their provider, NKF communications, or national outreach campaign. People self-enroll and share their data through a secure portal that offers individualized education and support. The first health system partner is Geisinger. Any cause and stage of CKD, including dialysis and kidney transplant recipients. Feasibility of the EHR data transfer, participants' characteristics, and their perspectives on usability and content. Data were collected and analyzed through the registry portal powered by the Pulse Infoframe healthie 2.0 platform. During the feasibility study, 80 participants completed their profile, and 42 completed a satisfaction survey. Mean age was 57.5 years, 51% were women, 83% were White, and 89% were non-Hispanic or Latino. Of the participants, 60% were not aware of their level of estimated glomerular filtration rate and 91% of their urinary albumin-creatinine ratio. Challenges for the Network are lack of awareness of kidney disease for many with CKD, difficulty in recruiting vulnerable populations or those with low digital readiness, and loss to follow-up, all leading to selection bias. The Network is positioned to become a national and international platform for real-world data that can inform the development of patient-centered research, care, and treatments.

Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients

Posttransplant hyperparathyroidism is common, and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of posttransplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients. Retrospective observational cohort study. We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B, and D-insured patients who received their first kidney transplant in 2007-2013. We excluded patients with pretransplant parathyroidectomy. Calendar year of transplantation and pretransplant patient characteristics. (1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years after transplant; (2) 90-day outcomes after posttransplant parathyroidectomy and cinacalcet initiation. Temporal trends and pretransplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively. The inclusion criteria were met by 30,127 patients, of whom 10,707 used cinacalcet before transplant, 551 underwent posttransplant parathyroidectomy, and 5,413 filled≥1 prescription for cinacalcet. The rate of posttransplant parathyroidectomy was stable over time. By contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pretransplant cinacalcet use were strongly associated with posttransplant parathyroidectomy and cinacalcet use. Roughly 1 in 4 patients were hospitalized within 90 days of posttransplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (vs cinacalcet initiation) was not associated with an increase in acute kidney injury. We lacked access to laboratory data to help assess the severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries. Almost one-fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for posttransplant hyperparathyroidism.

347.1: Unraveling the Stage-Shift of Acute Rejection in Renal Allografts

Introduction: The lack of accuracy in current allograft monitoring methodologies for allograft monitoring underscores a critical unmet need for more accurate immunosurveillance to uncover the flux in alloimmunity. QSant – a non-invasive, urine based multi-analyte diagnostic test – was clinically validated to prognosticate injury, risk of evolution, and resolution of acute rejection. QScore—the composite score across measurements of DNA markers: the amount of cell-free DNA, fraction of methylated cfDNA, protein and metabolic biomarkers in the QSant assay—enables this risk prognostication. This study now explores the clinical utility of QSant across the alloimmunity gradient of 32–100 for the early diagnosis of allograft injury and rejection. Methods: Utilizing a large real-world dataset of contemporaneous kidney allograft biopsy and QSant data from 11 US kidney transplant centers, the QScore offers a dynamic view into the changing state of allograft injury and rejection in response to alterations in the patients’ immunosuppression regimen. First analysis included Q-Score distributions in the biopsy-paired validation (n = 162) and prediction (n = 91) data from the Yang cohort, which were collected between 2010 and 2018 [10]. Second was a new analysis of a real-world data (RWD) cohort, comprising of prospectively collected urine samples (n = 235). Results: The RWD cohort (n = 235) of both adult and pediatric renal transplant patients demonstrated a spectrum across the Q-Score distribution. Specifically, 37.9% of the samples were enriched for immune quiescence (Q-Score < 32); the remaining 62.1% were enriched for the injury/rejection spectrum (Q-Score ≥ 32). The QScore <32 classifies stable allograft recipients; QScore between 32-55 exposes a state of alloimmunity flux; and the score between 55-100 provides advanced alloimmunity. Serial monitoring by QSant across a subset of 32 patients (RWD cohort,) over a period of two consecutive quarters (timepoints 1 and 2), captures the essence of the alloimmunity flux (p-value: 0.086 by non-parametric Wilcoxon test). Patients in the immunoquiescent domain (31% [10/32]) by and large continue to be stable (with Q-Scores that track at <32) 22% [7/32]). However, 9.4% (3/32) of patients show Q-Score drifts above 32 with evidence of early rejection. Patients in the alloimmune injury domain follow three trajectories: i) a planar gradient in QScore across time, showing persistence of alloimmunity; ii) an increasing gradient, delineating patients moving into the mature acute rejection domain; iii) a decreasing gradient, delineating patients moving into the immunoquiescent domain, putatively in response to immunomodulation following assessment of active rejection (Figure 1). Conclusion: The observed alloimmunity flux suggested precision monitoring with QSant has the potential to differentiate higher-grade acute rejection episodes from sub-clinical rejection, thereby improving a transplant recipient’s’ quality of life.

Implications of Accumulated Cold Time for US Kidney Transplantation Offer Acceptance.

Reducing discard is important for the US transplantation system because nearly 20% of the deceased donor kidneys are discarded. One cause for the discards is the avoidance of protracted cold ischemia times. Extended cold ischemia times at transplant are associated with additional risk of graft failure and patient mortality. A preference for local (within the same donor service area) or low-Kidney Donor Risk Index organs, the endogeneity of cold ischemia time during organ allocation, and the use of provisional offers all complicate the analysis of cold ischemia times' influence on kidney acceptance decision making. Using January 2018 to June 2019 Organ Procurement and Transplantation Network data, we modeled the probability of accepting an offer for a kidney after provisional acceptance. We use logistic regression that includes cold ischemia time, Kidney Donor Risk Index, and other covariates selected from literature. Endogeneity of cold ischemia time was treated by a two-stage instrumental variables approach. Logistic regression results for 3.33 million provisional acceptances from 12,369 donors and 108,313 candidates quantify trade-offs between cold ischemia time at the time of offer acceptance and donor-recipient characteristics. Overall, each additional 2 hours of cold ischemia time affected acceptance for nonlocal and local recipients (odds ratio, 0.75; 95% confidence interval, 0.73 to 0.77, odds ratio, 0.88; 95% confidence interval, 0.86 to 0.91; P<0.001). For Kidney Donor Risk Index >1.75 (Kidney Donor Profile Index >85) kidneys, an additional 2 hours of cold ischemia time for nonlocal and local recipients was associated with acceptance with odds ratio, 0.58; 95% confidence interval, 0.54 to 0.63 (nonlocal) and odds ratio, 0.65; 95% confidence interval, 0.6 to 0.7 (local); P<0.001. The effect of an additional 2 hours of cold ischemia time on acceptance of kidneys with Kidney Donor Risk Index ≤1.75 (Kidney Donor Profile Index ≤85) was less pronounced for nonlocal offers (odds ratio, 0.82; 95% confidence interval, 0.80 to 0.85; P<0.001) and not significant for local offers. The acceptability of marginal organs was higher when placements were nearer to the donor and when cold ischemia time was shorter.

Deceased Donor Procurement Biopsy Practices, Interpretation, and Histology-Based Decision-Making: A Survey of US Kidney Transplant Centers

IntroductionThe utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts.MethodsAn electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021–June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices.ResultsResponses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third of centers (35%) reported obtaining procurement biopsies on most-to-all kidneys. Most clinicians decided when to biopsy jointly with the Organ Procurement Organization (OPO) (82%) based on formal criteria for the decision (72%), although 41% reported having requested a biopsy outside of the criteria. Most respondents used a semiquantitative scoring system for interpretation (57%). Many respondents reported rarely or never having access to renal specialty pathologists (37%) or to telepathology (59%). Most respondents reported that a favorable biopsy result would encourage them to accept a "marginal" donor kidney (72%); nearly half (46%) indicated that an unfavorable biopsy result would lead to decline of a standard criteria kidney.ConclusionProcurement biopsies are commonly used in organ acceptance decisions despite inconsistent access to experienced renal pathologists and heterogeneous approaches to criteria, scoring, and interpretation. Ongoing study and consensus building are needed to direct procurement biopsy practice toward increasing organ utilization and reducing allocation inefficiency.