Preoperative Noncoronary Cardiovascular Assessment and Management of Kidney Transplant Candidates.

The pretransplant risk assessment for patients with ESKD who are undergoing evaluation for kidney transplant is complex and multifaceted. When considering cardiovascular disease in particular, many factors should be considered. Given the increasing incidence of kidney transplantation and the growing body of evidence addressing ESKD-specific cardiovascular risk profiles, there is an important need for a consolidated, evidence-based model that considers the unique cardiovascular challenges that these patients face. Cardiovascular physiology is altered in these patients by abrupt shifts in volume status, altered calcium-phosphate metabolism, high-output states (in the setting of arteriovenous fistulization), and adverse geometric and electrical remodeling, to name a few. Here, we present a contemporary review by addressing cardiomyopathy/heart failure, pulmonary hypertension, valvular dysfunction, and arrhythmia/sudden cardiac death within the ESKD population.

Evaluation of Accepting Kidneys of Varying Quality for Transplantation or Expedited Placement With Decision Trees.

BACKGROUND: Underutilization of marginal-quality kidneys for transplantation produced ideas of expediting kidney placement for populations with decreased opportunities of receiving transplants. Such policies can be less efficacious for specific individuals and should be scrutinized until the decision-making for accepting marginal-quality organs, which has relied on experiential judgment, is better understood at the individual level. There exist rigorous tools promoting personalized decisions with useful and objective information. METHODS: This article introduces a decision-tree methodology that analyzes a patient's dilemma: to accept a kidney offer now or reject it. The methodology calculates the survival benefit of accepting a kidney given a certain quality now and the survival benefit of rejecting it. Survival benefit calculation accounts for patients' and donors' characteristics and transplant centers' and organ procurement organizations' performances and incorporates patients' perceived transplant and dialysis utilities. Valuations of rejecting an offer are contingent on future opportunities and subject to uncertainty in the timing of successive kidney offers and their quality and donor characteristics. RESULTS: The decision tree was applied to a realistic patient profile as a demonstration. The tool was tested on 1000 deceased-donor kidney offers in 2016. Evaluating up to 1 year of future offers, the tool attains 61% accuracy, with transplant utility of 1.0 and dialysis utility of 0.5. The accuracy reveals potential bias in kidney offer acceptance/rejection at transplant centers. CONCLUSIONS: The decision-tree tool presented could aid personalized transplant decision-making in the future by providing patients with calculated, individualized survival benefits between accepting and rejecting a kidney offer.

Assessment and management of coronary artery disease in kidney and pancreas transplant candidates.

: Patients with end-stage renal disease (ESRD) undergoing evaluation for kidney and/or pancreas transplantation represent a population with unique cardiovascular (CV) profiles and unique therapeutic needs. Coronary artery disease (CAD) is common in patients with ESRD, mediated by both the overrepresentation and higher prognostic value of traditional CV risk factors amongst this population, as well as altered cardiovascular responses to failing renal function, likely mediated by dysregulation of the renin-angiotensin-aldosterone system (RAAS) and abnormal calcium and phosphate metabolism. Within the ESRD population, obstructive CAD correlates highly with adverse coronary events, including during the peri-transplant period, and successful revascularization may attenuate some of that increased risk. Accordingly, peri-transplant coronary risk assessment is critical to ensuring optimal outcomes for these patients. The following provides a review of CAD in patients being evaluated for kidney and/or pancreas transplantation, as well as evidence-based recommendations for appropriate peri-transplant evaluation and management.

Predictors of Deceased Donor Kidney Discard in the United States.

BACKGROUND: Renal transplantation is a lifesaving intervention for end-stage renal disease. The demand for renal transplantation outweighs the availability of organs; however, up to 20% of recovered kidneys are discarded before transplantation. We aimed to better characterize the risk factors for deceased donor kidney discard. METHODS: We performed a secondary analysis of the Organ Procurement and Transplantation Network database from 2000 to 2012 of all solid organ donors. The cohort was split into training (80%) and validation (20%) subsets. We performed a stepwise logistic regression to develop a multivariate risk prediction model for kidney graft discard and validated the model. The performance of the models was evaluated with respect to calibration, and area under the curve (AUC) of receiver operating characteristic curves. RESULTS: There were no significant baseline differences between the training (n = 57 474) and validation (n = 14 368) cohorts. The multivariate model validation showed very good discriminant function in predicting kidney discard (AUC = 0.84). Predictors of increased discard included age older than 50 years, performance of a kidney biopsy, cytomegalovirus seropositive status, donation after cardiac death, hepatitis B and C seropositive status, cigarette use, diabetes, hypertension, terminal creatinine greater than 1.5 mg/dL and AB blood type. The model outperformed the Kidney Donor Risk Index in predicting discard (P < 0.001). Subgroup analysis of expanded criteria donor kidneys demonstrated good discrimination with an AUC of 0.70. CONCLUSIONS: We have characterized several important predictors of deceased donor kidney discard. Better understanding of factors that lead to increased deceased donor kidney discard can allow for targeted interventions to reduce discard.

Allocating Deceased Donor Kidneys to Candidates with High Panel-Reactive Antibodies.

BACKGROUND AND OBJECTIVES: In December of 2014, the Organ Procurement and Transplant Network implemented a new Kidney Allocation System (KAS) for deceased donor transplant, with increased priority for highly sensitized candidates (calculated panel-reactive antibody [cPRA] >99%). We used a modified version of the new KAS to address issues of access and equity for these candidates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a simulation, 10,988 deceased donor kidneys transplanted into waitlisted recipients in 2010 were instead allocated to candidates with cPRA≥80% (n=18,004). Each candidate's unacceptable donor HLA antigens had been entered into the allocation system by the transplant center. In simulated match runs, kidneys were allocated sequentially to adult ABO identical or permissible candidates with cPRA 100%, 99%, 98%, etc. to 80%. Allocations were restricted to donor/recipient pairs with negative virtual crossmatches. RESULTS: The simulation indicated that 2111 of 10,988 kidneys (19.2%) would have been allocated to patients with cPRA 100% versus 74 of 10,988 (0.7%) that were actually transplanted. Of cPRA 100% candidates, 74% were predicted to be compatible with an average of six deceased donors; the remaining 26% seemed to be incompatible with every deceased donor organ that entered the system. Of kidneys actually allocated to cPRA 100% candidates in 2010, 66% (49 of 74) were six-antigen HLA matched/zero-antigen mismatched (HLA-A, -B, and -DR) with their recipients versus only 11% (237 of 2111) in the simulation. The simulation predicted that 10,356 of 14,433 (72%) candidates with cPRA 90%-100% could be allocated an organ compared with 7.3% who actually underwent transplant. CONCLUSIONS: Data in this simulation are consistent with early results of the new KAS; specifically, nearly 20% of deceased donor kidneys were (virtually) compatible with cPRA 100% candidates. Although most of these candidates were predicted to be compatible with multiple donors, approximately one-quarter are unlikely to receive a single offer.

Improving Geographic Equity in Kidney Transplantation Using Alternative Kidney Sharing and Optimization Modeling.

The national demand for kidney transplantation far outweighs the supply of kidney organs. Currently, a patient's ability to receive a kidney transplant varies depending on where he or she seeks transplantation. This reality is in direct conflict with a federal mandate from the Department of Health and Human Services. We analyze current kidney allocation and develop an alternative kidney sharing strategy using a multiperiod linear optimization model, KSHARE. KSHARE aims to improve geographic equity in kidney transplantation while also respecting transplant system constraints and priorities. KSHARE is tested against actual 2000-2009 kidney allocation using Organ Procurement and Transplant Network data. Geographic equity is represented by minimizing the range in kidney transplant rates around local areas of the country. In 2009, less than 25% of standard criteria donor kidneys were allocated beyond the local area of procurement, and Donor Service Area kidney transplantation rates varied from 3.0% to 30.0%, for an overall range of 27.0%. Given optimal sharing of kidneys within 600 miles of procurement for 2000-2009, kidney transplant rates vary from 5.0% to 12.5% around the country for an overall kidney transplant range of 7.5%. Nationally sharing kidneys optimally between local areas only further decreases the transplant rate range by 1.7%. Enhancing the practice of sharing kidneys by the KSHARE model may increase geographic equity in kidney transplantation.

Changes in geographic disparity in kidney transplantation since the final rule.

BACKGROUND: The national organ allocation system for deceased-donor kidney transplant will endure increased burden as the waitlist expands and organ shortage persists. The Department of Health and Human Services issued the "Final Rule" in 1998 that states "Organs and tissues ought to be distributed on the basis of objective priority criteria and not on the basis of accidents of geography." However, it has not been addressed whether the rule was effective in encouraging regions to share the additional burden equitably. OBJECTIVE: To assess the significance of changes of geographic disparities for four metrics since the rule's adoption: waiting times, transplant rates, pretransplant mortality, and organ quality. METHODS: Using Organ Procurement and Transplant Network data from 1988 through 2009, annual ranges of the metrics were calculated for all donor service areas and United Network for Organ Sharing regions. Time series analyses were used to compare the metrics before and after the enactment of the Final Rule. RESULTS: A total of 412,127 kidney transplant candidates and 178,163 deceased-donor recipients were analyzed. Demographics varied significantly by region. The ranges of the four metrics have worsened by approximately 30% or more after the Final Rule at both the regional and donor service area levels. CONCLUSION: Increasing geographic disparity in allocation procedures may yield diverging outcomes and experiences in different locations for otherwise similar candidates. Consensus for measuring allocation discrepancies and policy interventions are required to mitigate the inequities.

The effect of the Statewide Sharing variance on geographic disparity in kidney transplantation in the United States.

BACKGROUND AND OBJECTIVES: The Statewide Sharing variance to the national kidney allocation policy allocates kidneys not used within the procuring donor service area (DSA), first within the state, before the kidneys are offered regionally and nationally. Tennessee and Florida implemented this variance. Known geographic differences exist between the 58 DSAs, in direct violation of the Final Rule stipulated by the US Department of Health and Human Services. This study examined the effect of Statewide Sharing on geographic allocation disparity over time between DSAs within Tennessee and Florida and compared them with geographic disparity between the DSAs within a state for all states with more than one DSA (California, New York, North Carolina, Ohio, Pennsylvania, Texas, and Wisconsin). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective analysis from 1987 to 2009 was conducted using Organ Procurement and Transplant Network data. Five previously used indicators for geographic allocation disparity were applied: deceased-donor kidney transplant rates, waiting time to transplantation, cumulative dialysis time at transplantation, 5-year graft survival, and cold ischemic time. RESULTS: Transplant rates, waiting time, dialysis time, and graft survival varied greatly between deceased-donor kidney recipients in DSAs in all states in 1987. After implementation of Statewide Sharing in 1992, disparity indicators decreased by 41%, 36%, 31%, and 9%, respectively, in Tennessee and by 28%, 62%, 34%, and 19%, respectively in Florida, such that the geographic allocation disparity in Tennessee and Florida almost completely disappeared. Statewide kidney allocations incurred 7.5 and 5 fewer hours of cold ischemic time in Tennessee and Florida, respectively. Geographic disparity between DSAs in all the other states worsened or improved to a lesser degree. CONCLUSIONS: As sweeping changes to the kidney allocation system are being discussed to alleviate geographic disparity--changes that are untested run the risk of unintended consequences--more limited changes, such as Statewide Sharing, should be further studied and considered.

New national allocation policy for deceased donor kidneys in the United States and possible effect on patient outcomes.

In 2013, the Organ Procurement and Transplantation Network in the United States approved a new national deceased donor kidney allocation policy that introduces the kidney donor profile index (KDPI), which gives scores of 0%-100% based on 10 donor factors. Kidneys with lower KDPI scores are associated with better post-transplant survival. Important features of the new policy include first allocating kidneys from donors with a KDPI≤20% to candidates in the top 20th percentile of estimated post-transplant survival, adding waiting time from dialysis initiation, conferring priority points for a calculated panel-reactive antibody (CPRA)>19%, broader sharing of kidneys for candidates with a CPRA≥99%, broader sharing of kidneys from donors with a KDPI>85%, eliminating the payback system, and allocating blood type A2 and A2B kidneys to blood type B candidates. We simulated the distribution of kidneys under the new policy compared with the current allocation policy. The simulation showed increases in projected median allograft years of life with the new policy (9.07 years) compared with the current policy (8.82 years). With the new policy, candidates with a CPRA>20%, with blood type B, and aged 18-49 years were more likely to undergo transplant, but transplants declined in candidates aged 50-64 years (4.1% decline) and ≥65 years (2.7% decline). These simulations demonstrate that the new deceased donor kidney allocation policy may improve overall post-transplant survival and access for highly sensitized candidates, with minimal effects on access to transplant by race/ethnicity and declines in kidney allocation for candidates aged ≥50 years.

The DQ barrier: improving organ allocation equity using HLA-DQ information.

BACKGROUND: The United Network for Organ Sharing algorithm for deceased-donor kidney allocation considers only the human leukocyte antigen (HLA)-A, HLA-B, and HLA-DR loci. Although HLA-DQ serologic specificities can be entered as unacceptable antigens, they are assigned only by the identity of the DQß chain, disregarding the role of the similarly polymorphic α chain. DQα/ß combinations result in unique antigenic epitopes, which serve as targets to different antibodies. Therefore, the presence of HLA antibodies to one DQα/ß combination should not preclude negative crossmatch (XM) against another combination. In this retrospective analysis, patients were allowed XM against a particular donor if they had antibodies to some, but not all, DQα/ß allele combinations with the donor serologic HLA-DQ antigens. METHODS: HLA antibody signature was obtained using solid-phase Luminex-based antibody analysis. Results were captured at the high-resolution level (as provided by the positive beads). Potential donors were typed to include information on both HLA-DQA and HLA-DQB alleles. RESULTS: Of the 1130 flow XM assays performed, 147 patients had antibodies to donor serologic HLA-DQ antigens. Thirty-five of those patients had antibodies to an allelic DQα/ß combination within the donor serologic DQ specificity that were different from the donor's DQα/ß, leading to negative flow XM results (24%). Virtual XM, accounting for donor DQα/ß combinations, successfully predicts more than 98% of XM outcomes. CONCLUSIONS: In patients with allelic DQα/ß antibodies, denying the opportunity for XM based on serologically defined unacceptable antigens can disadvantage the patient. Larger cohort studies are required to substantiate our observation. Introducing DQα/ß combination information may increase virtual XM accuracy and organ allocation equity.