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.

Hispanic/Latino Disparities in Living Donor Kidney Transplantation: Role of a Culturally Competent Transplant Program.

UNLABELLED: Hispanic Americans face disparities in access to kidney transplantation, particularly living donor kidney transplantation (LDKT). This study compared characteristics of LDKT recipients before and after implementing the Hispanic Kidney Transplant Program (HKTP) at Northwestern Medicines (NM) and other centers. METHODS: The NM HKTP, initiated in December 2006, delivers culturally and linguistically competent and congruent care. Program-specific data were used to compare the mean ratios of Hispanic to non-Hispanic white LDKTs between pre-HKTP (2001-2006) and post-HKTP (2008-2013), and to compare the characteristics of NM's adult LDKT patients between pre-HKTP and post-HKTP. The same ratio was calculated for transplant centers in regions with a significant Hispanic population (≥25%) and performing in the top tertile of total LDKT volume in the pre-HKTP period. The number of Hispanic and non-Hispanic white patients added to the waiting list were compared between pre-HKTP (2001-2006) and post-HKTP (2008-2013) as a proxy for increased patient referrals and a pathway by which the HKTP may increase LDKTs. RESULTS: The ratio of Hispanic to non-Hispanic white LDKTs significantly increased by 70% after the implementation of NM's HKTP (pre-HKTP mean = 0.20, post-HKTP mean = 0.34; P= 0.001). None of the other transplant centers experienced a similar increase in their ratio of Hispanic to non-Hispanic white LDKTs. The NM waiting list additions grew by 91% among Hispanics, but grew only 4% for non-Hispanic whites. CONCLUSIONS: These data suggest that the development and implementation of a culturally congruent transplant program can positively affect Hispanic LDKT and thereby reduce Hispanics disparities in LDKT rates. Further studies are needed to prospectively evaluate the generalizability of implementing such culturally competent interventions at other transplant programs.

Simulation modeling of the impact of proposed new simultaneous liver and kidney transplantation policies.

BACKGROUND: Increasing use of kidney grafts for simultaneous liver and kidney (SLK) transplants is causing concern about the most effective utilization of scarce kidney graft resources. This study evaluated the impact of implementing the proposed United Network for Organ Sharing SLK transplant policy on outcomes for end-stage liver disease (ESLD) and end-stage renal disease (ESRD) patients awaiting transplant. METHODS: A Markov model was constructed to simulate a hypothetical cohort of ESLD patients over a 30-year time horizon starting from age 50. The model applies the different criteria being considered in the United Network for Organ Sharing policy and tallies outcomes, including numbers of procedures and life years after liver transplant alone (LTA) or SLK transplant. RESULTS: When 1-week pretransplant dialysis duration is required, the numbers of SLK transplants and LTAs would be 648 and 9,065, respectively. If the pretransplant dialysis duration is extended to 12 weeks, there would be 240 SLK transplants and 9,426 LTAs. This change results in a decrease of 6,483 life years among SLK transplant recipients and an increase of 4,971 life years among LTA recipients. However, by increasing the dialysis duration to 12 weeks from 1 week, 408 kidney grafts would be released to the kidney waitlist because of the decline in SLK transplants; this yields 796 additional life years gained among ESRD patients. CONCLUSION: Implementation of the proposed SLK transplant policy could restore access to kidney transplants for patients with ESRD albeit at the detriment of patients with ESLD and renal impairment.

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.

Detection of medical errors in kidney transplantation: a pilot study comparing proactive clinician debriefings to a hospital-wide incident reporting system.

BACKGROUND: Rates of medical errors and adverse events remain high for patients who undergo kidney transplantation; they are particularly vulnerable because of the complexity of their disease and the kidney transplantation procedure. Although institutional incident-reporting systems are used in hospitals around the country, they often fail to capture a substantial proportion of medical errors. The goal of this study was to assess the ability of a proactive, web-based clinician safety debriefing to augment the information about medical errors and adverse events obtained via traditional incident reporting systems. METHODS: Debriefings were sent to all individuals listed on operating room personnel reports for kidney transplantation surgeries between April 2010 and April 2011, and incident reports were collected for the same time period. The World Health Organization International Classification for Patient Safety was used to classify all issues reported. RESULTS: A total of 270 debriefings reported 334 patient safety issues (179 safety incidents, 155 contributing factors), and 57 incident reports reported 92 patient safety issues (56 safety incidents, 36 contributing factors). Compared with incident reports, more attending physicians completed the debriefings (32.0 vs 3.5%). DISCUSSION: The use of a proactive, web-based debriefing to augment an incident reporting system in assessing safety risks in kidney transplantation demonstrated increased information, more perspectives of a single safety issue, and increased breadth of participants.

Comparative effectiveness of liver transplant strategies for end-stage liver disease patients on renal replacement therapy.

There are complex risk-benefit tradeoffs with different transplantation strategies for end-stage liver disease patients on renal support. Using a Markov discrete-time state transition model, we compared survival for this group with 3 strategies: simultaneous liver-kidney (SLK) transplantation, liver transplantation alone (LTA) followed by immediate kidney transplantation if renal function did not recover, and LTA followed by placement on the kidney transplant wait list. Patients were followed for 30 years from the age of 50 years. The probabilities of events were synthesized from population data and clinical trials according to Model for End-Stage Liver Disease (MELD) scores (21-30 and >30) to estimate input parameters. Sensitivity analyses tested the impact of uncertainty on survival. Overall, the highest survival rates were seen with SLK transplantation for both MELD score groups (82.8% for MELD scores of 21-30 and 82.5% for MELD scores > 30 at 1 year), albeit at the cost of using kidneys that might not be needed. Liver transplantation followed by kidney transplantation led to higher survival rates (77.3% and 76.4%, respectively, at 1 year) than placement on the kidney transplant wait list (75.1% and 74.3%, respectively, at 1 year). When uncertainty was considered, the results indicated that the waiting time and renal recovery affected conclusions about survival after SLK transplantation and liver transplantation, respectively. The subgroups with the longest durations of pretransplant renal replacement therapy and highest MELD scores had the largest absolute increases in survival with SLK transplantation versus sequential transplantation. In conclusion, the findings demonstrate the inherent tension in choices about the use of available kidneys and suggest that performing liver transplantation and using renal transplantation only for those who fail to recover their native renal function could free up available donor kidneys. These results could inform discussions about transplantation policy.

Comparative effectiveness of donation after cardiac death versus donation after brain death liver transplantation: Recognizing who can benefit.

Due to organ scarcity and wait-list mortality, transplantation of donation after cardiac death (DCD) livers has increased. However, the group of patients benefiting from DCD liver transplantation is unknown. We studied the comparative effectiveness of DCD versus donation after brain death (DBD) liver transplantation. A Markov model was constructed to compare undergoing DCD transplantation with remaining on the wait-list until death or DBD liver transplantation. Differences in life years, quality-adjusted life years (QALYs), and costs according to candidate Model for End-Stage Liver Disease (MELD) score were considered. A separate model for hepatocellular carcinoma (HCC) patients with and without MELD exception points was constructed. For patients with a MELD score <15, DCD transplantation resulted in greater costs and reduced effectiveness. Patients with a MELD score of 15 to 20 experienced an improvement in effectiveness (0.07 QALYs) with DCD liver transplantation, but the incremental cost-effectiveness ratio (ICER) was >$2,000,000/QALY. Patients with MELD scores of 21 to 30 (0.25 QALYs) and >30 (0.83 QALYs) also benefited from DCD transplantation with ICERs of $478,222/QALY and $120,144/QALY, respectively. Sensitivity analyses demonstrated stable results for MELD scores <15 and >20, but the preferred strategy for the MELD 15 to 20 category was uncertain. DCD transplantation was associated with increased costs and reduced survival for HCC patients with exception points but led to improved survival (0.26 QALYs) at a cost of $392,067/QALY for patients without exception points. In conclusion, DCD liver transplantation results in inferior survival for patients with a MELD score <15 and HCC patients receiving MELD exception points, but provides a survival benefit to patients with a MELD score >20 and to HCC patients without MELD exception points.

Quality of life, risk assessment, and safety research in liver transplantation: new frontiers in health services and outcomes research.

PURPOSE OF REVIEW: In this review, we briefly summarize three fruitful, emerging areas in liver transplantation research, quality of life; risk assessment; and patient safety. Our goal is to highlight recent findings in these areas, with a call for increased integration of social scientists and transplant clinicians to address how best to shape policy and improve outcomes. RECENT FINDINGS: After liver transplantation, recipients generally experience clinically significant, sustained improvement in their physical, social and emotional well being. However, a sizeable minority of patients do experience excess morbidity that may benefit from ongoing surveillance and/or intervention. There is growing body of research that describes risks associated with liver transplantation, which can be useful aids to better inform decision making by patients, clinicians, payers, and policy makers. In contrast, there has been a relative lack of empirical data on transplant patient safety vulnerabilities, placing the field of surgery in stark contrast to other high-risk industries, wherein such assessments inform continuous process improvement. SUMMARY: Health services and outcomes research has grown in importance in the liver transplantation literature, but several important questions remain unanswered that merit programmatic, interdisciplinary research.

Cardiovascular risk assessment of the liver transplant candidate.

Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.

A comprehensive risk assessment of mortality following donation after cardiac death liver transplant - an analysis of the national registry.

BACKGROUND & AIMS: Organ scarcity has resulted in increased utilization of donation after cardiac death (DCD) donors. Prior analysis of patient survival following DCD liver transplantation has been restricted to single institution cohorts and a limited national experience. We compared the current national experience with DCD and DBD livers to better understand survival after transplantation. METHODS: We compared 1113 DCD and 42,254 DBD recipients from the Scientific Registry of Transplant Recipients database between 1996 and 2007. Patient survival was analyzed using the Kaplan-Meier methodology and Cox regression. RESULTS: DCD recipients experienced worse patient survival compared to DBD recipients (p<0.001). One and 3 year survival was 82% and 71% for DCD compared to 86% and 77% for DBD recipients. Moreover, DCD recipients required re-transplantation more frequently (DCD 14.7% vs. DBD 6.8%, p<0.001), and re-transplantation survival was markedly inferior to survival after primary transplant irrespective of graft type. Amplification of mortality risk was observed when DCD was combined with cold ischemia time >12h (HR = 1.81), shared organs (HR = 1.69), recipient hepatocellular carcinoma (HR=1.80), recipient age >60 years (HR = 1.92), and recipient renal insufficiency (HR = 1.82). CONCLUSIONS: DCD recipients experience significantly worse patient survival after transplantation. This increased risk of mortality is comparable in magnitude to, but often exacerbated by other well-established risk predictors. Utilization decisions should carefully consider DCD graft risks in combination with these other factors.

The increased costs of donation after cardiac death liver transplantation: caveat emptor.

OBJECTIVE: To determine the effect of donation after cardiac death (DCD) livers on post-transplantation costs. BACKGROUND: DCD livers are increasingly being used to expand the donor pool despite higher complication rates. Although complications after liver transplantation have profound financial implications, the effect of DCD livers on post-transplantation costs has not been studied. METHODS: We estimated direct medical care costs based on inpatient and outpatient hospital costs for 28 DCD and 198 donation after brain death (DBD) liver recipients. Organ acquisition and physician costs were excluded. RESULTS: Donor and recipient demographics were comparable for DCD and DBD transplants. One-year, post-transplantation costs were higher for DCD recipients (124.9% of DBD costs, P = 0.04). DCD costs remained higher (125.2% of DBD costs, P = 0.009) after adjusting for recipient characteristics. Furthermore, DCD post-transplantation costs were 30% higher than DBD costs after adjusting for pre-transplantation costs (P = 0.02). Biliary complications (DCD 58% vs. DBD 21%; P < 0.001) and, specifically, ischemic cholangiopathy (DCD 44% vs. DBD 1.6%; P < 0.001) occurred more frequently after DCD transplantation. Moreover, DCD recipients underwent retransplantation more often (DCD 21% vs. DBD 7.1%, P = 0.02). One-year costs were increased for recipients with ischemic cholangiopathy or retransplantation by 53% (P = 0.01) and 107% (P < 0.001), respectively. However, DCD costs continued to be higher when retransplanted patients were excluded (120% of DBD costs, P = 0.02). CONCLUSIONS: Higher rates of graft failure and biliary complications translate into markedly increased direct medical care costs for DCD recipients. These important financial implications should be considered in decisions regarding the use of DCD livers.