Planning for Uncertainty and Fallbacks Can Increase the Number of Transplants in a Kidney-Paired Donation Program.

A kidney-paired donation (KPD) pool consists of transplant candidates and their incompatible donors, along with nondirected donors (NDDs). In a match run, exchanges are arranged among pairs in the pool via cycles, as well as chains created from NDDs. A problem of importance is how to arrange cycles and chains to optimize the number of transplants. We outline and examine, through example and by simulation, four schemes for selecting potential matches in a realistic model of a KPD system; proposed schemes take account of probabilities that chosen transplants may not be completed as well as allowing for contingency plans when the optimal solution fails. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Donation, the simulations extend over 8 match runs, with 30 pairs and 1 NDD added between each run. Schemes that incorporate uncertainties and fallbacks into the selection process yield substantially more transplants on average, increasing the number of transplants by as much as 40% compared to a standard selection scheme. The gain depends on the degree of uncertainty in the system. The proposed approaches can be easily implemented and provide substantial advantages over current KPD matching algorithms.

Transplanting kidneys without points for HLA-B matching: consequences of the policy change.

In 2003, the US kidney allocation system was changed to eliminate priority for HLA-B similarity. We report outcomes from before and after this change using data from the Scientific Registry of Transplant Recipients (SRTR). Analyses were based on 108 701 solitary deceased donor kidney recipients during the 6 years before and after the policy change. Racial/ethnic distributions of recipients in the two periods were compared (chi-square); graft failures were analyzed using Cox models. In the 6 years before and after the policy change, the overall number of deceased donor transplants rose 23%, with a larger increase for minorities (40%) and a smaller increase for non-Hispanic whites (whites) (8%). The increase in the proportion of transplants for non-whites versus whites was highly significant (p < 0.0001). Two-year graft survival improved for all racial/ethnic groups after implementation of this new policy. Findings confirmed prior SRTR predictions. Following elimination of allocation priority for HLA-B similarity, the deficit in transplantation rates among minorities compared with that for whites was reduced but not eliminated; furthermore, there was no adverse effect on graft survival.

Geographic variation in end-stage renal disease incidence and access to deceased donor kidney transplantation.

The effect of demand for kidney transplantation, measured by end-stage renal disease (ESRD) incidence, on access to transplantation is unknown. Using data from the U.S. Census Bureau, Centers for Medicare & Medicaid Services (CMS) and the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) from 2000 to 2008, we performed donation service area (DSA) and patient-level regression analyses to assess the effect of ESRD incidence on access to the kidney waiting list and deceased donor kidney transplantation. In DSAs, ESRD incidence increased with greater density of high ESRD incidence racial groups (African Americans and Native Americans). Wait-list and transplant rates were relatively lower in high ESRD incidence DSAs, but wait-list rates were not drastically affected by ESRD incidence at the patient level. Compared to low ESRD areas, high ESRD areas were associated with lower adjusted transplant rates among all ESRD patients (RR 0.68, 95% CI 0.66-0.70). Patients living in medium and high ESRD areas had lower transplant rates from the waiting list compared to those in low ESRD areas (medium: RR 0.68, 95% CI 0.66-0.69; high: RR 0.63, 95% CI 0.61-0.65). Geographic variation in access to kidney transplant is in part mediated by local ESRD incidence, which has implications for allocation policy development.

Access and outcomes among minority transplant patients, 1999-2008, with a focus on determinants of kidney graft survival.

Coincident with an increasing national interest in equitable health care, a number of studies have described disparities in access to solid organ transplantation for minority patients. In contrast, relatively little is known about differences in posttransplant outcomes between patients of specific racial and ethnic populations. In this paper, we review trends in access to solid organ transplantation and posttransplant outcomes by organ type, race and ethnicity. In addition, we present an analysis of categories of factors that contribute to the racial/ethnic variation seen in kidney transplant outcomes. Disparities in minority access to transplantation among wait-listed candidates are improving, but persist for those awaiting kidney, simultaneous kidney and pancreas and intestine transplantation. In general, graft and patient survival among recipients of solid organ transplants is highest for Asians and Hispanic/Latinos, intermediate for whites and lowest for African Americans. Although much of the difference in outcomes between racial/ethnic groups can be accounted for by adjusting for patient characteristics, important observed differences remain. Age and duration of pretransplant dialysis exposure emerge as the most important determinants of survival in an investigation of the relative impact of center-related versus patient-related variables on kidney graft outcomes.

Kidney and pancreas transplantation in the United States, 1997-2006: the HRSA Breakthrough Collaboratives and the 58 DSA Challenge.

Growth in the number of active patients on the kidney transplant waiting list has slowed. Projections based on the most recent 5-year data suggest the total waiting list will grow at a rate of 4138 registrations per year, whereas the active waiting list will increase at less than one-sixth that rate, or 663 registrations per year. The last 5 years have seen a small trend toward improved unadjusted allograft survival for living and deceased donor kidneys. Since 2004 the overall number of pancreas transplants has declined. Among pancreas recipients, those with simultaneous kidney-pancreas transplants experienced the highest pancreas graft survival rates. In response to the ongoing shortage of deceased donor organs, the US Health Resources and Services Administration launched the Organ Donation Breakthrough Collaborative in September 2003 and the Organ Transplantation Breakthrough Collaborative (OTBC) in October 2005. The 58 DSA Challenge is prominent among the goals adopted by the OTBC. Its premise: were each of the 58 existing donation service areas to increase the number of kidney transplants performed within their boundaries by 10 per month, an additional 7000 transplants over current annual levels would result. Such an increase could potentially eliminate the national kidney transplantation waiting list by 2030.

Transplants in Foreign Countries Among Patients Removed from the US Transplant Waiting List.

Transplant tourism, where patients travel to foreign countries specifically to receive a transplant, is poorly characterized. This study examined national data to determine the minimum scope of this practice. US national waiting list removal data were analyzed. Waiting list removals for transplant without a corresponding US transplant in the database were reviewed via a data validation query to transplant centers to identify foreign transplants. Additionally, waiting list removal records with text field entries indicating a transplant abroad were identified. We identified 373 foreign transplants (173 directly noted; 200 from data validation); most (89.3%) were kidney transplants. Between 2001 and 2006, the annual number of waiting list removals for transplant abroad increased. Male sex, Asian race, resident and nonresident alien status and college education were significantly and independently associated with foreign transplant. Recipients from 34 states, plus the District of Columbia, received foreign transplants in 35 countries, led by China, the Philippines and India. Transplants in foreign countries among waitlisted candidates in the US are increasingly performed. The data reported here represent the minimum number of cases and the full extent of this practice cannot be determined using existing data. Additional reporting requirements are needed.

Geographic variability in access to primary kidney transplantation in the United States, 1996-2005.

This article focuses on geographic variability in patient access to kidney transplantation in the United States. It examines geographic differences and trends in access rates to kidney transplantation, in the component rates of wait-listing, and of living and deceased donor transplantation. Using data from Centers for Medicare and Medicaid Services and the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients, we studied 700,000+ patients under 75, who began chronic dialysis treatment, received their first living donor kidney transplant, or were placed on the waiting list pre-emptively. Relative rates of wait-listing and transplantation by State were calculated using Cox regression models, adjusted for patient demographics. There were geographic differences in access to the kidney waiting list and to a kidney transplant. Adjusted wait-list rates ranged from 37% lower to 64% higher than the national average. The living donor rate ranged from 57% lower to 166% higher, while the deceased donor transplant rate ranged from 60% lower to 150% higher than the national average. In general, States with higher wait-listing rates tended to have lower transplantation rates and States with lower wait-listing rates had higher transplant rates. Six States demonstrated both high wait-listing and deceased donor transplantation rates while six others, plus D.C. and Puerto Rico, were below the national average for both parameters.

Analytical methods and database design: implications for transplant researchers, 2005.

Understanding how transplant data are collected is crucial to understanding how the data can be used. The collection and use of Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) data continues to evolve, leading to improvements in data quality, timeliness and scope while reducing the data collection burden. Additional ascertainment of outcomes completes and validates existing data, although caveats remain for researchers. We also consider analytical issues related to cohort choice, timing of data submission, and transplant center variations in follow-up data. All of these points should be carefully considered when choosing cohorts and data sources for analysis. The second part of the article describes some of the statistical methods for outcome analysis employed by the SRTR. Issues of cohort and follow-up period selection lead into a discussion of outcome definitions, event ascertainment, censoring and covariate adjustment. We describe methods for computing unadjusted mortality rates and survival probabilities, and estimating covariate effects through regression modeling. The article concludes with a description of simulated allocation modeling, developed by the SRTR for comparing outcomes of proposed changes to national organ allocation policies.

Differences in access to cadaveric renal transplantation in the United States.

This national study compares waitlisting and transplantation rates by gender, race, and diabetes and evaluates physiologic factors (panel-reactive antibodies [PRA], blood type, HLA matchability) and related practices (early and multiple waitlisting) as explanatory factors. This longitudinal study of the time to transplant waitlisting among 228,552 incident end-stage renal disease (ESRD) dialysis patients and to cadaveric transplantation among 46,164 waitlist dialysis patients (n = 23,275 first cadaveric transplants) used US data for 1991 to 1997. Relative rates of waitlisting (RRWL) after ESRD onset and of cadaveric transplantation (RRTx) after waitlist (Cox proportional hazards models) were adjusted for age, race, sex, ESRD cause, region, and incidence/waitlist year. We found that women have an RRWL = 0.84 (P < 0.0001) and RRTx = 0.86 (P < 0. 0001). PRA levels can explain the difference in the transplantation rate, because accounting for PRA gives an adjusted RRTx = 0.98 (NS) for women. For blacks versus whites, the RRWL = 0.59 (P < 0.0001) and RRTx = 0.55 (P < 0.0001). However, the transplantation rate can only partly be explained by ABO types, rare HLA types, and early and multiple waitlisting (adjusted RRTx = 0.67 [P < 0.0001]). For diabetes versus glomerulonephritis, the RRWL = 0.52 (P < 0.0001) and RRTx = 0.98 (NS). Older patients (40 to 59 years of age) are less likely to be waitlisted and to receive a transplant after waitlisting (RRWL = 0.57 [P < 0.0001], RRTx = 0.88 [P < 0.0001]) versus younger patients (ages 18 to 39 years). These results indicate substantial differences by age, sex, race, and diabetes in rates of waitlisting for transplantation and by age and race for transplantation after waitlisting. These differences by race were not explained by referral practices or the physiologic factors studied here.

Body size, dose of hemodialysis, and mortality.

This study investigates the role of body size on the mortality risk associated with dialysis dose in chronic hemodialysis patients. A national US random sample from the US Renal Data System was used for this observational longitudinal study of 2-year mortality. Prevalent hemodialysis patients treated between 1990 and 1995 were included (n = 9,165). A Cox proportional hazards model, adjusting for patient characteristics, was used to calculate the relative risk (RR) for mortality. Both dialysis dose (equilibrated Kt/V [eKt/V]) and body size (body weight, body volume, and body mass index) were independently and significantly (P < 0.01 for each measure) inversely related to mortality when adjusted for age and diabetes. Mortality was less among larger patients and those receiving greater eKt/V. The overall association of mortality risk with eKt/V was negative and significant in all patient subgroups defined by body size and by race-sex categories in the range 0.6 < eKt/V < 1.6. The association was negative in the restricted range 0.9 < eKt/V < 1.6 (although not generally significant) for all body-size subgroups and for three of four race-by-sex subgroups, excepting black men (RR = 1. 003/0.1 eKt/V; P > 0.95). These findings suggest that dose of dialysis and several measures of body size are important and independent correlates of mortality. These results suggest that patient management protocols should attempt to ensure both good patient nutrition and adequate dose of dialysis, in addition to managing coexisting medical conditions.

Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.

BACKGROUND AND METHODS: The extent to which renal allotransplantation - as compared with long-term dialysis - improves survival among patients with end-stage renal disease is controversial, because those selected for transplantation may have a lower base-line risk of death. In an attempt to distinguish the effects of patient selection from those of transplantation itself, we conducted a longitudinal study of mortality in 228,552 patients who were receiving long-term dialysis for end-stage renal disease. Of these patients, 46,164 were placed on a waiting list for transplantation, 23,275 of whom received a first cadaveric transplant between 1991 and 1997. The relative risk of death and survival were assessed with time-dependent nonproportional-hazards analysis, with adjustment for age, race, sex, cause of end-stage renal disease, geographic region, time from first treatment for end-stage renal disease to placement on the waiting list, and year of initial placement on the list. RESULTS: Among the various subgroups, the standardized mortality ratio for the patients on dialysis who were awaiting transplantation (annual death rate, 6.3 per 100 patient-years) was 38 to 58 percent lower than that for all patients on dialysis (annual death rate, 16.1 per 100 patient-years). The relative risk of death during the first 2 weeks after transplantation was 2.8 times as high as that for patients on dialysis who had equal lengths of follow-up since placement on the waiting list, but at 18 months the risk was much lower (relative risk, 0.32; 95 percent confidence interval, 0.30 to 0.35; P<0.001). The likelihood of survival became equal in the two groups within 5 to 673 days after transplantation in all the subgroups of patients we examined. The long-term mortality rate was 48 to 82 percent lower among transplant recipients (annual death rate, 3.8 per 100 patient-years) than patients on the waiting list, with relatively larger benefits among patients who were 20 to 39 years old, white patients, and younger patients with diabetes. CONCLUSIONS: Among patients with end-stage renal disease, healthier patients are placed on the waiting list for transplantation, and long-term survival is better among those on the waiting list who eventually undergo transplantation.