Improve Organ Utilization Research Articles

A call to action: Feasible strategies to reduce the discard of transplantable kidneys in the United States

Changes to the United States kidney allocation system targeted at reducing organ discard have failed to improve organ utilization. High Kidney Donor Profile Index kidneys continue to be discarded at high rates as a result of the regulatory and financial barriers to widespread utilization of these organs. However, there are potential changes to clinical practice that could improve organ utilization. Expediting the time from initial offer to final organ acceptance would reduce cold ischemic time and should improve utilization. Implementation of procurement biopsy standards to avoid biopsy of low risk organs may prevent organ discards due to inaccurate data or excessive cold ischemia time. Further, standardization of procurement biopsy pathological interpretation coupled with electronic accessibility would enable early acceptance of difficult to transplant organs. These changes to allocation practice patterns are vital given proposals to expand the geographic sharing of deceased donor kidneys. Implementation of new allocation policies must be evaluated to ensure they result in higher transplant rates and acceptable post-transplant outcomes.

Mobile Application for Communication Increases the Efficiency of Organ Procurement and Transplantation.

Background:Donor organ recovery is a complex process involving organ procurement organizations and multiple surgical teams from various transplant centers. Nearly 30% of discarded organs are wasted due to reasons related to improper coordination and communication.Problem Statement:Lack of real-time communication results in many hours of preventable delay between procurement and transplant teams resulting in the high volume of organ waste, clinical frustration, and critical delays.Methods:A Plan-Do-Study-Act performance improvement methodology was utilized to design and implement a dedicated mobile communication application (app). Critical time points in the organ offer, procurement, and transplant processes were analyzed from the Report of Organ Offers, and relation coordination metrics were measured.Processes Addressed:Members of procurement and transplant teams in Iowa were interviewed and a dedicated smartphone application was implemented to replace phone calls, e-mails, faxes, and text messages during upcoming kidney offers from July 31, 2017 to July 31, 2018.Outcomes:Teams reported a substantial increase in clinical productivity and case progress awareness, including a noteworthy reduction in phone calls. The relational coordination data indicated substantially higher relationship and communication quality with the app. The Report of Organ Offer data revealed a 35% increase in organs transplanted and a 50% reduction in time from initial organ offer to transplant with the use of the mobile application.Implications for Practice:The use of a dedicated communication application reduces clinical frustration and delays during the coordination of organ offer, procurement, and transplant. Technologies that improve communication have the potential to improve organ utilization.

Expanding the donor pool for congenital heart disease transplant candidates by implementing 3D imaging-derived total cardiac volumes.

Heart transplant waitlist mortality remains high in infants <1year of age and among those with CHD. Currently, the median accepted donor-to-recipient weight percentage is approximately 130% of the recipient's weight. We hypothesized that patients with CHD may accept a larger organ using novel 3D-derived imaging data to estimate donor and recipient TCV. A single-center, retrospective study was performed using CT data for 13 patients with CHD and 94 control patients. 3D visualization software was used to create digital 3D heart models that provide an estimate of TCV. In addition, echocardiograms obtained prior to cross-sectional imaging were reviewed for presence of ventricular chamber dilation. Sixty-two percent (8/13) of patients with CHD had 3D-derived TCV resulting in a weight that was >130% larger than their actual weight. This was seen in single-ventricle patients following Blalock-Taussig shunt and Fontan palliation, and patients with biventricular repair. Of those, 75% (6/8) had reported moderate-to-severe ventricular chamber dilation by echocardiogram or cardiac magnetic resonance imaging. In a large portion of patients with CHD, 3D-derived TCV place the recipient at a higher listing weight than their actual weight. We propose obtaining cross-sectional imaging to better assess TCV in a recipient, which may increase the donor range for CHD recipients and improve organ utilization in pediatrics.

Pre-implantation kidney biopsy: value of the expertise in determining histological score and comparison with the whole organ on a series of discarded kidneys.

Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist's expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys. 46 discarded kidneys were identified with their corresponding biopsies. The biopsies were reviewed by three general and two specialist pathologists, blinded to the original report, according to Remuzzi score. The intraclass correlation coefficient (ICC) was calculated for both groups. Discarded kidneys were scored according to Remuzzi score by a single specialist pathologist. Biopsies and organs were compared by Wilcoxon signed rank test. Weighted κ coefficients between biopsy and organ scores were also calculated. Specialist pathologists achieved higher values of ICC, reaching excellent or good agreement in most of the parameters, while general pathologists values were mainly fair or good. On whole organs, scores were consistently lower than biopsies, with a significant difference in most of the parameters. Weighted κ coefficient was slight or fair for most of the parameters. Our data suggests that the creation of a pool of specialist pathologists would improve organ utilization. Moreover, biopsies are not representative of the whole organ. As the Remuzzi score on biopsy is a major reasons for discard, a quota of transplantable kidneys may be erroneously discarded. Refinement in Remuzzi cut-offs based on expert reporting and recognition of sampling error of biopsies in correlation with clinical outcome data should be undertaken.

Deceased Brain Dead Donor Liver Transplantation and Utilization in the United States: Nighttime and Weekend Effects.

Understanding factors that contribute to liver discards and nonusage is urgently needed to improve organ utilization. Using Scientific Registry of Transplant Recipient data, we studied a national cohort of all US adult, deceased brain dead donor, isolated livers available for transplantation from 2003 to 2016, including organ-specific and system-wide factors that may affect organ procurement and discard rates. Of 73 686 available livers, 65 316 (88.64%) were recovered for transplant, of which 6454 (9.88%) were ultimately discarded. Livers that were not procured or, on recovery, discarded were more frequently from older, heavier, hepatitis B virus (HCV)+, and more comorbid donors (P < 0.001). However, even after adjustment for organ quality, the odds of liver nonusage were 11% higher on the weekend (defined as donor procurements with cross-clamping occurring from 5:00 PM Friday until 11:59 AM Sunday) compared with weekdays (P < 0.001). Nonuse rates were also higher at night (P < 0.001), defined as donor procurements with cross-clamping occurring from 5:00 PM to 5:00 AM; however, weekend nights had significantly higher nonuse rates compared with weekday nights (P = 0.005). After Share 35, weekend nonusage rates decreased from 21.77% to 19.51% but were still higher than weekday nonusage rates (P = 0.065). Weekend liver nonusage was higher in all 11 United Network of Organ Sharing regions, with an absolute average of 2.00% fewer available livers being used on the weekend compared with weekdays. Although unused livers frequently have unfavorable donor characteristics, there are also systemic and operational factors, including time of day and day of the week a liver becomes available, that impact the chance of liver nonprocurement and discard.

Impact of US Public Health Service increased risk deceased donor designation on organ utilization.

Under US Public Health Service guidelines, organ donors with risk factors for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) are categorized as increased risk donors (IRD). Previous studies have suggested that IRD organs are utilized at lower rates than organs from standard risk donors (SRD), but these studies were conducted prior to universal donor nucleic acid test screening. We conducted risk-adjusted analyses to determine the effect of IRD designation on organ utilization using 2010-2017 data (21626 heart, 101160 kidney, 52714 liver, and 16219 lung recipients in the United States) from the Organ Procurement and Transplantation Network. There was no significant difference (P<.05) between risk-adjusted utilization rates for IRD vs SRD organs for adult hearts and livers and pediatric kidneys, livers, and lungs. Significantly lower utilization was found among IRD adult kidneys, lungs, and pediatric hearts. Analysis of the proportion of transplanted organs recovered from IRD by facility suggests that a subset of facilities contribute to the underutilization of adult IRD kidneys. Along with revised criteria and nomenclature to identify donors with HIV, HBV, or HCV risk factors, educational efforts to standardize informed consent discussions might improve organ utilization.

Normothermic Machine Perfusion (NMP) Inhibits Proinflammatory Responses in the Liver and Promotes Regeneration.

Liver transplantation (LT) is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of patients losing their chance of a transplant attributed to liver decompensation (LD) and death. Ischemia/reperfusion injury (IRI) following conventional cold storage (CS) is a major cause of injury leading to graft loss after LT. Normothermic machine perfusion (NMP), a method of organ preservation, provides oxygen and nutrition during preservation and allows aerobic metabolism. NMP has recently been shown to enable improved organ utilization and posttransplant outcomes following a phase I and a phase III randomized trial. The aim of the present study is to assess the impact of NMP on reducing IRI and to define the underlying mechanisms. We transplanted and compared 12 NMP with 27 CS-preserved livers by performing gene microarray, immunoprofiling of hepatic lymphocytes, and immunochemistry staining of liver tissues for assessing necrosis, platelet deposition, and neutrophil infiltration, and the status of steatosis after NMP or CS prereperfusion and postreperfusion. Recipients receiving NMP grafts showed significantly lower peak aspartate aminotransferase (AST) levels than those receiving CS grafts. NMP altered gene-expression profiles of liver tissue from proinflammation to prohealing and regeneration. NMP also reduced the number of interferon gamma (IFN-γ) and interleukin (IL)-17-producing T cells and enlarged the CD4pos CD25high CD127neg FOXP3pos regulatory T cell (Treg) pool. NMP liver tissues showed less necrosis and apoptosis in the parenchyma and fewer neutrophil infiltration compared to CS liver tissues. Conclusion: Reduced IRI in NMP recipients was the consequence of the combination of inhibiting inflammation and promoting graft regeneration.

KAS Turns Four: The State of Deceased Donor Kidney Allocation in the U.S.

Background: This study examines very recent trends in deceased donor kidney transplantation to assess the performance of the kidney allocation system (KAS), implemented December 4, 2014, and whether bolus effects associated with KAS have stabilized nearly four years after implementation. Methods: The overall number of deceased donor kidney transplants, as well as the proportion of transplants by recipient and transplant characteristics, were calculated monthly from December 2013 through September 2018 and examined graphically. Kidney discard rates – the percentage of kidneys recovered for transplant not transplanted – were analyzed overall and stratified by donor Kidney Donor Profile Index (KDPI). Delayed graft function (DGF) was defined as the recipient requiring dialysis within one week of transplant; monthly rates were examined graphically. We also surveyed other published research to round out our assessment of KAS’s impact. Results: Marked bolus effects, particularly a sharp increase in transplants to highly sensitized and high dialysis time recipients, were associated with KAS implementation but have since stabilized. Transplant access has improved for African American candidates, who now receive a proportion of transplants comparable to their representation on the waiting list. Subtype-compatible (“A2/A2B to B”) transplants have increased sharply but are still numerically small (~20/month) and may have plateaued. Though the overall kidney discard rate has not changed appreciably over the past five years, the rate for KDPI 35-85% kidneys has trended slightly downward since 2017. After initially rising with KAS, DGF rates have tapered but still remain slightly above pre-KAS levels. One-year graft and patient survival remain excellent. Conclusions: The number of deceased donor kidney transplants has reached an all-time high and continues to rise, a boon for the nearly 100,000 patients with kidney failure on the waiting list. Several key bolus effects that were anticipated with KAS did indeed materialize, drastically changing the characteristics of the initial wave of post-KAS recipients. These bolus effects have since tapered, suggesting KAS has, by and large, reached a steady state. KAS has improved equity across ethnicities and levels of sensitization but did not attempt to resolve geographic inequities. Published research has confirmed that substantial geographic disparities remain. The goal of increasing utilization of kidneys at high risk of discard has not been met. Numerous policy changes and system improvement initiatives have been proposed, many of which are currently underway or pending implementation, to improve organ utilization.

Machine perfusion in transplantation (Sponsor: Novartis Pharma GmbH, Nürnberg)

AbstractThe preservation of donor organs through machine perfusion (MP) creates new opportunities in transplantation medicine for the benefit of patients. In view of the organ shortage and the increasing number of marginal organs, there is a need to establish MP in Germany in order to improve organ utilization and therapeutic outcomes. In kidney transplantation, the use of MP can significantly improve 1-year survival. MP also offers advantages in liver, heart, and lung transplantation. As recommended by the Organ Donation Committee (KfO, Kommission für Organspende) of the German Transplantation Society (DTG, Deutsche Transplantationsgesellschaft) as well as the Permanent Committee on Organ Transplantation (StäKO, Ständige Kommission Organtransplantation), its use should be initially adopted in standard care in the form of hypothermic machine perfusion in kidney transplantation and then be further extended.

Timing of hepatitis C virus infection treatment in kidney transplant candidates.

Hepatitis C virus (HCV) infection is prevalent in patients with kidney disease including transplant candidates and recipients. It is associated with increased morbidity and mortality in end-stage renal disease patients and also increases the risk of allograft rejection and decreases allograft and patient survival post-transplant. Newly developed direct acting antivirals have revolutionized the way HCV is treated. Whether patients are treated before or after kidney transplantation, the cure rates with direct acting antivirals are >90%. Great debate has formed revolving the optimal timing to treat kidney transplant candidates. On the one hand, treatment before transplantation decreases early post-transplant complications related to HCV. On the other, postponing treatment until after transplantation opens the possibility of transplanting a kidney from a HCV positive donor, which is associated with shorter waiting time and improved organ utilization by expanding the organ donor pool. Most patients living in an area where waiting time is reduced by accepting an HCV positive kidney would benefit by the strategy of treatment post-transplantation, but this decision needs to be individualized in a patient-by-patient basis given that there are special circumstances (i.e., severe HCV-related extrahepatic manifestations, availability of live donors, etc.) in which treatment before transplant might be preferred.

Invited Commentary

Invited Commentary

Heart Transplantation Survival and Sex-Related Differences.

Orthotopic heart transplantation (OHT) is the "gold standard" treatment for patients with end-stage heart failure, with approximately 5000 transplants performed each year worldwide. Heart transplantation survival rates have progressively improved at all time points, despite an increase in donor and recipient age and comorbidity and greater recipient urgency; according to the registry of the International Society of Heart and Lung Transplantation (ISHLT), the median survival of patients posttransplantation is currently 12.2years.Long-term survival is sub-optimal, and outcomes after OHT remain constrained by the development of acute rejection and cardiac allograft vasculopathy (CAV). Moreover, donor organs are in short supply, making optimal organ utilization an ongoing priority. For these reasons, substantial interest continues to exist in identifying factors portending increased survival and improved organ utilization.

(736) - Durable Ventricular Assist Devices for Infants Improve Organ Utilization and Survival

(736) - Durable Ventricular Assist Devices for Infants Improve Organ Utilization and Survival

Is Donor Service Area Market Competition Associated With Organ Procurement Organization Performance?

Organ procurement organizations (OPOs) are currently evaluated on donation rates and number of organs per donor. However, there is significant variability in market characteristics which affect transplant programs' donor organ acceptance practices and OPOs' ability to successfully place higher risk organs. The impact of transplant market characteristics on OPO performance metrics has not been evaluated. The OPO performance measures were correlated annually with the Herfindahl Hirschman Index, a standard measure of market competition for centers within the OPO donor service areas from 2003 to 2011. More competitive donor service areas were associated with increased number of donors (P = 0.01) and eligible deaths (P < 0.001). Market competition was associated with increased use of high Donor Risk Index for kidney (P = 0.03) and liver (P = 0.01) allografts. The OPOs with increased competition in liver transplant also were noted to have a higher donor conversion rate (P < 0.001), more donors per million population (P < 0.001), and a higher utilization rate for liver allografts (P = 0.007). These data suggest that proposals to increase district size to increase competition among transplant programs could result in improved organ utilization over time by incentivizing the use of marginal donor organs and increasing access to transplantation.

Deceased Organ Donor Research: The Last Research Frontier?

Deceased Organ Donor Research: The Last Research Frontier?

Lung and Heart Allocation in the United States

Lung and heart allocation in the United States has evolved over the past 20-30 years to better serve transplant candidates and improve organ utilization. The current lung allocation policy, based on the Lung Allocation Score, attempts to take into account risk of death on the waiting list and chance of survival posttransplant. This policy is flexible and can be adjusted to improve the predictive ability of the score. Similarly, in response to the changing clinical phenotype of heart transplant candidates, heart allocation policies have evolved to a multitiered algorithm that attempts to prioritize organs to the most infirm, a designation that fluctuates with trends in therapy. The Organ Procurement and Transplantation Network and its committees have been responsive, as demonstrated by recent modifications to pediatric heart allocation and mechanical circulatory support policies and by ongoing efforts to ensure that heart allocation policies are equitable and current. Here we examine the development of US lung and heart allocation policy, evaluate the application of the current policy on clinical practice and explore future directions for lung and heart allocation.

Balancing Multiple and Conflicting Allocation Goals: A Logical Path Forward

Balancing Multiple and Conflicting Allocation Goals: A Logical Path Forward

Viral Nucleic Acid Testing (NAT) and OPO-Level Disposition of High-Risk Donor Organs

The use of Public Health Service/Centers for Disease Control and Prevention (PHS/CDC) high-risk donor (HRD) organs remains controversial, especially in light of a recent high-profile case of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission. Nucleic acid testing (NAT), while more expensive and time consuming, reduces infectious risk by shortening the period between infection and detectability. The purpose of this study was to characterize HRDs and disposition of their organs by organ procurement organization (OPO), to measure NAT practices by OPO and to examine associations between NAT practices and use of HRD organs. We analyzed 29 950 deceased donors (2574 HRDs) reported to UNOS since July 1, 2004 and May 8, 2008. We then surveyed all OPO clinical directors about their use of NAT, average time to receive NAT results, locations where NAT is performed and percentage of the time NAT results are available for allocation decisions. In total, 51.7% of OPOs always perform HIV NAT, while 24.1% never do. A similar pattern is seen for HCV NAT performance, while the majority (65.6%) never perform HBV NAT. AIDS prevalence in an OPO service area is not associated with NAT practice. OPOs that perform HIV NAT are less likely to export organs outside of their region. The wide variation of current practice and the possibility that NAT would improve organ utilization support consideration for a national policy.

Risk Factor Analysis in Pediatric Heart Transplantation

Steady assessment of risk factors will enable identification of patients at higher risk for post-transplant death, and may thus improve organ utilization and outcomes. In this study we aimed to identify the risk factors of mortality in pediatric heart transplantation. Between November 1989 and February 2004, there were 116 orthotopic heart transplantations performed in patients <18 years of age at our institution. The 30-day mortality risk was 12% (dilated cardiomyopathy 7%, congenital heart disease 26%; univariate analysis: p = 0.023). The main cause of 30-day mortality was primary graft failure (36%). The late mortality rate was 31 per 1,000 person-years. The main causes of late mortality were acute rejection (44%) and cardiac allograft vasculopathy (26%). The 1-, 5-, 10- and 15-year survival rates were 85%, 77%, 65% and 53%, respectively. Male donor (odds ratio [OR] 6.33, 95% confidence interval [CI] 1.11 to 36.01) and cardiopulmonary bypass >210 minutes (OR 43.05, 95% CI 1.11 to 1,669) were risk factors for 30-day mortality. Risk factors for 1- and 5-year mortality were body weight ratio <0.8 (OR 40.36, 95% CI 3.04 to 536.47) and male donor (OR 3.36, 95% CI 1.05 to 10.75), respectively. Recipient age <1 year (OR 64.65, 95% CI 1.69 to 2,466.77) and donor-recipient body surface area mismatch of <0.9 (OR 10.58, 95% CI 1.03 to 108.25) were risk factors for 10-year mortality. Pediatric heart transplantation can be performed with an expectation of excellent results. Certain risk factors suggest poorer outcomes.

Organ utilization among deceased donors in Canada, 1993–2002

Optimizing organ utilization from consented donors is a critical need, given a static organ donation rate. We report changes in the characteristics of donors and organ utilization patterns in Canada over a ten-year period. For the decade spanning the years 1993-2002, data were extracted from the Canadian Organ Replacement Register (CORR), the national transplant registry. A donor was defined as a deceased person from whom at least one vital organ was retrieved and transplanted. The donor pool is aging (median age of donors increased eight years over the decade), with proportionately fewer donors dying from head trauma (motor vehicle collisions) and proportionately more from cerebrovascular accidents. At least four organs were utilized from approximately half the donors. These donors were significantly younger every year over the sampling period when compared with donors where < or = three organs were utilized. In 2002, utilization rates were: 87.0% (kidneys), 85.0% (livers), 42.2% (hearts), 30.6% (pancreata), 28.3% (lungs), and < or = 1% (intestines). There was increased utilization of donor pancreata, lungs and liver over the decade, but a flat utilization pattern for hearts, and a small decline in kidney utilization. Utilization rates vary from province to province. Trends in the Canadian organ donor pool are characterized by an increasing age and a shift towards cerebrovascular diseases as primary causes of death. In order to improve organ utilization and understand regional variability, the scope of data provided to the national registry requires enhanced detail to address the factors that lead to non-utilization. Addressing the low utilization rates for hearts and lungs is especially critical, given the need for thoracic transplantation in Canada.