Hospitalization patterns before and after liver transplantation.

BACKGROUND: Mortality among patients with chronic liver failure is significantly reduced upon liver transplantation. However, decreases in mortality may not be accompanied by decreases in morbidity metrics, such as hospitalization rates. We compared pre- and posttransplant hospitalization rates for liver transplant recipients. METHODS: Statewide hospitalization data were analyzed among 215 adult chronic liver failure patients in Pennsylvania who received a deceased donor transplant from September 2001 to December 2002. Generalized estimating equation (GEE) models were fitted to compare covariate-adjusted pre- and posttransplant hospital admission rates and mean length of stay per admission. The study minimized biases by calculating pre- and posttransplant morbidity in a cohort restricted to patients who received a transplant and were compared to themselves. RESULTS: Liver transplant recipients experienced a significant 70% reduction in hospitalization rates (P<0.0001) posttransplant versus pretransplant. The decline, which occurred for all Model for End-Stage Liver Disease (MELD) subgroups, was significant for patients transplanted at all MELD scores except 6-9. However, even patients with MELD 6-9 experienced a significant decrease in mean length of stay, post versus pretransplant. Higher MELD scores at transplant were generally associated with a greater reduction in hospitalization rates. Also, patients transplanted with lower MELD scores appeared to receive lower quality livers. CONCLUSIONS: Our results indicate that the benefit of transplantation extends beyond patient survival and that an important reduction in hospitalization rates is experienced by transplanted patients. Further study is required to determine whether these results are generalizable to the entire United States and to evaluate the donor liver quality used for recipients of different MELD scores.

Preemptive transplantation for patients with diabetes-related kidney disease.

BACKGROUND: Preemptive kidney transplantation (PreKT) before initiation of chronic dialysis has been examined recently with favorable results as the most effective treatment for kidney failure. Given that few of these studies are disease specific, the present analyses investigated the outcomes of PreKT by transplantation option and diabetes type. METHODS: The impact of PreKT on posttransplantation mortality and graft failure was examined in 23 238 adults with type 1 and type 2 diabetes mellitus (DM), receiving either living or deceased donor kidneys or undergoing simultaneous pancreas-kidney (SPK) transplantation between January 1, 1997, and December 31, 2002. RESULTS: The PreKTs were provided to 14.4% of patients with type 1 DM and 6.7% of patients with type 2 DM. Cox regression models were used to estimate the effect of PreKT on the adjusted risk ratio (RR) of graft failure and mortality. After adjusting for multiple factors, PreKT in this era was associated with lower RR of mortality only among type 1 and type 2 diabetic recipients of transplants from living donors and SPK transplant recipients with type 1 DM (RR, 0.50-0.65; P<.007 for each). The effect on graft failure was less pronounced, significant only for preemptive SPK transplant recipients (RR, 0.79; P=.01 vs nonpreemptive SPK transplant recipients). CONCLUSIONS: These analyses suggest that PreKT has significant benefits for subsets of patients with types 1 and 2 DM and end-stage renal disease. It also suggests a time trend toward less benefit from preemptive transplants from deceased donors in more recent years compared with the early 1990s. This observation and the discrepancies between RR of graft loss and RR of mortality deserve further study.

Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors.

BACKGROUND: Availability of cadaveric kidneys for transplantation is far below the growing need, leading to longer waiting time and more deaths while waiting. METHODS: Using national data from 1995 to 2000, we evaluated graft survival by donor characteristics and the rate of discard of retrieved organs, with the goal of increasing use of kidneys that are associated with increased risk of graft failure, that is, expanded donor kidneys. RESULTS: Cox models identified four donor factors that independently predicted significantly higher relative risk of graft loss compared with a low-risk group. These factors included donor age, cerebrovascular accident as the cause of death, renal insufficiency (serum creatinine >1.5 mg/dL), and history of hypertension. Expanded donor kidneys were defined as those with relative risk of graft loss greater than 1.70 and included all donors aged 60 years and older and those aged 50 to 59 years with at least two of the other three conditions (cerebrovascular cause of death, renal insufficiency, hypertension). The expanded donor group accounted for 14.8% of transplanted kidneys. Among organs procured from expanded donors, 38% were discarded versus 9% for all other kidneys. The risk of graft loss of expanded donor kidneys was increased in both older and younger recipients but to a greater extent in those recipients older than 50 years. CONCLUSION: By identifying donor factors associated with graft failure, these analyses may help to expand the number of transplanted kidneys by increasing the utilization of retrieved cadaveric kidneys.

Association between vascular access failure and the use of specific drugs: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Several drugs have been proposed to improve vascular access patency based on favorable anticoagulant, antiplatelet, or vascular-remodeling properties. However, there is little evidence to guide drug strategies. METHODS: The association between vascular access patency and the use of specific drugs was studied in a large sample of US hemodialysis patients enrolled in the Dialysis Outcomes and Practice Patterns Study, an international, prospective, observational study. In general, it was assumed that the drugs were prescribed for indications unrelated to vascular access preservation. Primary (unassisted survival) and secondary vascular access patency (assisted survival) were modeled using Cox regression (time to failure) adjusted for age, sex, race, body mass index, incidence to end-stage renal disease, diabetes mellitus, hypertension, valvular disease, chronic obstructive pulmonary disease, aortic aneurysm, deep-vein thrombosis, number of previous permanent accesses, and facility-clustering effects. Fistulae (n = 900) and grafts (n = 1,944) were evaluated separately. Technical failures within the first 30 days of surgical placement were excluded from the analysis. RESULTS: Treatment with calcium channel blockers was associated with improved primary graft patency (relative risk [RR] for failure, 0.86; P = 0.034). Aspirin therapy was associated with better secondary graft patency (RR, 0.70; P < 0.001). Treatment with angiotensin-converting enzyme inhibitors was associated with significantly better secondary fistula patency (RR, 0.56; P = 0.010). Patients administered warfarin showed worse primary graft patency (RR, 1.33; P = 0.037). CONCLUSION: These findings should help guide clinical trial priorities toward vascular access preservation using one or more of the agents that show significant risk reduction for access failure in this study.

Evaluation of the ESRD managed care demonstration operations.

Individuals with end stage renal disease (ESRD), most of whom are insured by Medicare, are generally prohibited from enrolling in Medicare managed care plans (MCPs). CMS offered ESRD patients the opportunity to participate in an ESRD managed care demonstration mandated by Congress. The demonstration tested whether managed care systems would be of interest to ESRD patients and whether these approaches would be operationally feasible and efficient for treating ESRD patients. This article examines the structure, implementation, and operational outcomes of the three demonstration sites, focusing on: the structure of these managed care programs for ESRD patients, requirements needed to attract and enroll patients, and the challenges of introducing managed care programs in the ESRD arena.

Patient selection in the ESRD managed care demonstration.

The Centers for Medicare & Medicaid Service's (CMS') end stage renal disease (ESRD) managed care demonstration offered an opportunity to assess patient selection among a chronically ill and inherently costly population. Patient selection refers to the phenomenon whereby those Medicare beneficiaries who choose to enroll or stay in health maintenance organizations (HMOs) are, on average, younger, healthier, and less costly to treat than beneficiaries who remain in the traditional Medicare fee-for-service (FFS) sector. The results presented in this article show that enrollees into the demonstration were generally younger and healthier than a representative group of comparison patients from the same geographic areas.

ESRD managed care demonstration: financial implications.

In 1996, CMS launched the end stage renal disease (ESRD) managed care demonstration to study the experience of offering managed care to ESRD patients. This article analyzes the financial impact of the demonstration, which sought to assess its economic impact on the Federal Government, the sites, and the ESRD Medicare beneficiaries. Medicare's costs for demonstration enrollees were greater than they would have been if these enrollees had remained in the fee-for-service (FFS) system. This loss was driven by the lower than average predicted Medicare spending given the demonstration patients' conditions. The sites experienced losses or only modest gains, primarily because they provided a larger benefit package than traditional Medicare coverage, including no patient obligations and other benefits, especially prescription drugs. Patient financial benefits were approximately $9,000 annually.

Quality of life and patient satisfaction: ESRD managed care demonstration.

To study the effects of managed care on dialysis patients, we compared the quality of life and patient satisfaction of patients in a managed care demonstration with three comparison samples: fee-for-service (FFS) patients, managed care patients outside the demonstration, and patients in a separate national study. Managed care patients were less satisfied than FFS patients about access to health care providers, but more satisfied with the financial benefits (copayment coverage, prescription drugs, and nutritional supplements) provided under the demonstration managed care plan (MCP). After 1 year in the demonstration, patients exhibited statistically and clinically significant increases in quality of life scores.

Use of a pediatric end-stage liver disease score for deceased donor allocation: the United States experience.

The Pediatric end-stage liver disease (PELD) score was developed as a measure of the severity of chronic liver disease that would predict mortality or children awaiting liver transplant. From multivariate analyses a model was derived that included five objective factors which together comprise the PELD score. The factors are growth failure, age less than 1 year, international normalized ratio (INR), serum albumin and total bilirubin.

The survival benefit of liver transplantation.

Demand for liver transplantation continues to exceed donor organ supply. Comparing recipient survival to that of comparable candidates without a transplant can improve understanding of transplant survival benefit. Waiting list and post-transplant mortality was studied among a cohort of 12 996 adult patients placed on the waiting list between 2001 and 2003. Time-dependent Cox regression models were fitted to determine relative mortality rates for candidates and recipients. Overall, deceased donor transplant recipients had a 79% lower mortality risk than candidates (HR = 0.21; p < 0.001). At Model for End-stage Liver Disease (MELD) 18-20, mortality risk was 38% lower (p < 0.01) among recipients compared to candidates. Survival benefit increased with increasing MELD score; at the maximum score of 40, recipient mortality risk was 96% lower than that for candidates (p < 0.001). In contrast, at lower MELD scores, recipient mortality risk during the first post-transplant year was much higher than for candidates (HR = 3.64 at MELD 6-11, HR = 2.35 at MELD 12-14; both p < 0.001). Liver transplant survival benefit at 1 year is concentrated among patients at higher risk of pre-transplant death. Futile transplants among severely ill patients are not identified under current practice. With 1 year post-transplant follow-up, patients at lower risk of pre-transplant death do not have a demonstrable survival benefit from liver transplant.

Transplant data: sources, collection and research considerations, 2004.

The process of collecting and analyzing transplant data is complex. Familiarity with how these data are collected is crucial to a thorough understanding of the information. This article focuses on available OPTN-SRTR data and the continuing evolution of data collection mechanisms; how that data collection system is improving the data quality and reducing the data collection burden; how additional ascertainment of outcomes both completes and validates existing data; and caveats that remain for researchers. This year's article focuses further on research considerations related to cohort choice, timing of data submission, and potential biases in follow-up data. Ongoing improvements in data collection timeliness and scope are covered. The impact of extra ascertainment of outcomes, particularly for post-transplant kidney graft failure from Medicare data, are also examined. A section on graft failure reporting among different sources traces the steps by which the SRTR reconciles different data sources in its analyses. It is important that those reading and conducting transplant research understand the origin, structure, and scope of the available data. All of these issues should be carefully considered when choosing cohorts and data sources for analysis.

Analytical approaches for transplant research, 2004.

This article provides detailed explanations of the methods frequently employed in outcomes analyses performed by the Scientific Registry of Transplant Recipients (SRTR). All aspects of the analytical process are discussed, including cohort selection, post-transplant follow-up analysis, outcome definition, ascertainment of events, censoring, and adjustments. The methods employed for descriptive analyses are described, such as unadjusted mortality rates and survival probabilities, and the estimation of covariant effects through regression modeling. A section on transplant waiting time focuses on the kidney and liver waiting lists, pointing out the different considerations each list requires and the larger questions that such analyses raise. Additionally, this article describes specialized modeling strategies recently designed by the SRTR and aimed at specific organ allocation issues. The article concludes with a description of simulated allocation modeling (SAM), which has been developed by the SRTR for three organ systems: liver, thoracic organs, and kidney-pancreas. SAMs are particularly useful for comparing outcomes for proposed national allocation policies. The use of SAMs has already helped in the development and implementation of a new policy for liver candidates with high MELD scores to be offered organs regionally before the organs are offered to candidates with low MELD scores locally.

Selection of pediatric candidates under the PELD system.

1. The PELD score accurately predicts the 3 month probability of waiting list death for children with chronic liver disease. 2. Comparing pre and post PELD and MELD implementation, the percent of children receiving deceased donor livers increased and the percent of children dying on the list decreased after PELD/MELD implementation. 3. Excluding children transplanted at status 1, the largest percentage of children are transplanted at a PELD score < 10. 4. Before MELD/PELD 48% of all children receiving deceased donor organs were transplanted at status 1, compared to 41% in the PELD/MELD era. Wide regional variation occurs.

Improving liver allocation: MELD and PELD.

On February 27, 2002, the liver allocation system changed from a status-based algorithm to one using a continuous MELD/PELD severity score to prioritize patients on the waiting list. Using data from the Scientific Registry of Transplant Recipients, we examine and discuss several aspects of the new allocation, including the development and evolution of MELD and PELD, the relationship between the two scoring systems, and the resulting effect on access to transplantation and waiting list mortality. Additional considerations, such as regional differences in MELD/PELD at transplantation and the predictive effects of rapidly changing MELD/PELD, are also addressed. Death or removal from the waiting list for being too sick for a transplant has decreased in the MELD/PELD era for both children and adults. Children younger than 2 years, however, still have a considerably higher rate of death on the waiting list than adults. A limited definition of ECD livers suggests that they are used more frequently for patients with lower MELD scores.

Hemodialysis vascular access preferences and outcomes in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Synthetic grafts have generally been found to exhibit lower survival rates and higher complication rates than native arteriovenous fistulae. We investigated whether survival of grafts relative to fistulae was better in facilities with a preference for grafts, hypothesizing that such facilities may place more grafts because grafts produced superior outcomes. METHODS: The study was based on a national U.S. sample of 133 hemodialysis facilities participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational study of dialysis treatment practices and outcomes. Vascular access preferences were ascertained from medical directors, nurse managers, and actual practice within each facility (% graft use among prevalent patients). Logistic regression was used to model the odds ratio (OR) of graft placement (vs. fistula) and Cox regression was used to model time from access creation to initial failure. RESULTS: Grafts were preferred by 21% of medical directors and 40% of nurse managers. Patients in facilities in which the medical director or nurse manager expressed a preference for grafts were more than twice as likely to have a graft than a fistula (AOR = 2.3, P < 0.01; reference group = facilities that did not prefer grafts), suggesting that facility preferences influence the type of access created. Overall, grafts were more prevalent than fistulae in dialysis facilities, but displayed a higher relative risk of failure (RR 1.33, P < 0.0001). However, the risk of graft versus fistula failure did not vary by expressed preference of the medical director: the relative risk of graft versus fistula failure was 1.39 in facilities in which the medical director preferred grafts and 1.39 in facilities in which the medical director preferred fistulae. Moreover, the relative risk of graft versus fistula failure was 1.57 in facilities that used more than the median percentage of grafts and 1.19 in facilities that used less than the median percentage of grafts. CONCLUSIONS: No evidence was found that graft outcomes are superior in facilities that prefer grafts to fistulae. The observed variation in vascular access practice patterns suggests opportunities for quality improvement if optimal practices can be defined.

Longitudinal assessment of mortality risk among candidates for liver transplantation.

Liver allocation policy recently was modified to use the Model for End-Stage Liver Disease (MELD) for patients with chronic liver disease to stratify potential recipients according to risk for waitlist death. In this study, a retrospective cohort of 760 adult patients with chronic liver disease placed on the liver transplant waitlist between January 1995 and March 2001 and followed up for up to 74 months was studied to assess the ability of the MELD to predict mortality among waitlisted candidates and evaluate the prognostic importance of changes in MELD score over time. Serial MELD scores predicted waitlist mortality significantly better than baseline MELD scores or medical urgency status. Each unit of the 40-point MELD score was associated with a 22% increased risk for waitlist death (P <.001), whereas medical urgency status was not a significant independent predictor. For any given MELD score, the magnitude and direction of change in MELD score during the previous 30 days (DeltaMELD) was a significant independent mortality predictor. Patients with MELD score increases greater than 5 points over 30 days had a threefold greater waitlist mortality risk than those for whom MELD scores increased more gradually (P <.0001). We conclude that mortality risk on the liver transplant waitlist is predicted more accurately by serial MELD score determinations than by medical urgency status or single MELD measurements. DeltaMELD score over time reflects progression of liver disease and conveys important additional prognostic information that should be considered in the further evolution of national liver allocation policy.

Predicted lifetimes for adult and pediatric split liver versus adult whole liver transplant recipients.

Split liver transplantation allows 2 recipients to receive transplants from one organ. Comparisons of predicted lifetimes for two alternatives (split liver for an adult and pediatric recipient vs. whole liver for an adult recipient) can help guide the use of donor livers. We analyzed mortality risk for 48,888 waitlisted candidates, 907 split and 21,913 whole deceased donor liver transplant recipients between January 1, 1995 and February 26, 2002. Cox regression models for pediatric and adult patients assessed average relative wait list and post-transplant death risks, for split liver recipients. Life years gained compared with remaining on the waiting list over a 2-year period were calculated. Seventy-six splits (152 recipients) and 24 re-transplants resulted from every 100 livers (13.1% [adult] and 18.0% [pediatric] 2-year re-transplant rates, respectively). Whole livers used for 93 adults also utilized 100 livers (re-transplant rate 7.0%). Eleven extra life years and 59 incremental recipients accrued from each 100 livers used for split compared with whole organ transplants. Split liver transplantation could provide enough organs to satisfy the entire current demand for pediatric donor livers in the United States, provide more aggregate years of life than whole organ transplants and result in larger numbers of recipients.

Analytical approaches for transplant research.

It is highly desirable to base decisions designed to improve medical practice or organ allocation policies on the analyses of the most recent data available. Yet there is often a need to balance this desire with the added value of evaluating long-term outcomes (e.g. 5-year mortality rates), which requires the use of data from earlier years. This article explains the methods used by the Scientific Registry of Transplant Recipients in order to achieve these goals simultaneously. The analysis of waiting list and transplant outcomes depends strongly on statistical methods that can combine data from different cohorts of patients that have been followed for different lengths of time. A variety of statistical methods have been designed to address these goals, including the Kaplan-Meier estimator, Cox regression models, and Poisson regression. An in-depth description of the statistical methods used for calculating waiting times associated with the various types of organ transplants is provided. Risk of mortality and graft failure, adjusted analyses, cohort selection, and the many complicating factors surrounding the calculation of follow-up time for various outcomes analyses are also examined.

Survival benefit of kidney and liver transplantation for obese patients on the waiting list.

As in the general population of the United States, obesity has become a significant problem in transplantation. Patient survival after deceased donor kidney transplantation is significantly lower among obese recipients (body mass index [BMI] > or = 30 kg/m2) than among non-obese recipients. Survival also appears to be decreased among obese liver transplant recipients. Based on these findings, some authors have argued against kidney or liver transplantation in the morbidly obese. However, the survival benefit for patients listed for and receiving either a kidney or liver transplant is not well understood. To determine if a significant survival benefit exists for obese patients after transplantation versus those on the waiting list, we studied a retrospective cohort of patients identified in the Scientific Registry of Transplant Recipients database. Adjusted, time-dependent Cox regression models were used to evaluate the relative risk (RR) of death after transplantation compared with waiting list mortality for either kidney or liver transplantation. These results demonstrate that kidney transplantation offers a significant survival benefit and is the preferred therapy for most obese dialysis patients. Although liver transplant recipients with a BMI > or = 35 kg/m2 had an increased RR for mortality compared with other recipients with a lower BMI, all groups, regardless of BMI, demonstrated a significant transplant benefit. These data suggest obesity should not be a contraindication for transplantation.

Vascular access use in Europe and the United States: results from the DOPPS.

BACKGROUND: A direct broad-based comparison of vascular access use and survival in Europe (EUR) and the United States (US) has not been performed previously. Case series reports suggest that vascular access practices differ substantially in the US and EUR. We report on a representative study (DOPPS) which has used the same data collection protocol for> 6400 hemodialysis (HD) patients to compare vascular access use at 145 US dialysis units and 101 units in five EUR countries (France, Germany, Italy, Spain, and the United Kingdom). METHODS: Logistic analysis evaluated factors associated with native arteriovenous fistula (AVF) versus graft use or permanent access versus catheter use for prevalent and incident HD patients. Times to failure for AVF and graft were analyzed using Cox proportional hazards regression. RESULTS: AVF was used by 80% of EUR and 24% of US prevalent patients, and was significantly associated with younger age, male gender, lower body mass index, non-diabetic status, lack of peripheral vascular disease, and no angina. After adjusting for these factors, AVF versus graft use was still much higher in EUR than US (AOR=21, P < 0.0001). AVF use within facilities varied from 0 to 87% (median 21%) in the US, and 39 to 100% (median 83%) in EUR. For patients who were new to HD, access use was: 66% AVF in EUR versus 15% in US (AOR=39, P < 0.0001), 31% catheters in EUR vs. 60% in US, and 2% grafts in EUR vs. 24% in US. In addition, 25% of EUR and 46% of US incident patients did not have a permanent access placed prior to starting HD. In EUR, 84% of new HD patients had seen a nephrologist for> 30 days prior to ESRD compared with 74% in the US (P < 0.0001); pre-ESRD care was associated with increased odds of AVF versus graft use (AOR=1.9, P=0.01). New HD patients had a 1.8-fold greater odds (P=0.002) of starting HD with a permanent access if a facility's typical time from referral to access placement was < or =2 weeks. AVF use when compared to grafts was substantially lower (AOR=0.61, P=0.04) when surgery trainees assisted or performed access placements. When used as a patient's first access, AVF survival was superior to grafts regarding time to first failure (RR=0.53, P=0.0002), and AVF survival was longer in EUR compared with the US (RR=0.49, P=0.0005). AVF and grafts each displayed better survival if used when initiating HD compared with being used after patients began dialysis with a catheter. CONCLUSION: Large differences in vascular access use exist between EUR and the US, even after adjustment for patient characteristics. The results strongly suggest that a facility's preferences and approaches to vascular access practice are major determinants of vascular access use.