Moving from Intuition to Data: Building the Evidence to Support and Increase Living Donor Kidney Transplantation

• kidney transplantation
• living donation
• systematic review
• disparities
• Living Donors
• Intuition
• kidney

Living donor kidney transplantation (LDKT) offers patients with ESRD the best chance for long-term survival (1). Although kidney transplantation, in general, affords better outcomes than long-term dialysis, LDKT provides benefits over deceased donor kidney transplantation, including faster access to transplant, with less time on dialysis and its associated risks, and superior long-term patient and allograft survival at lower cost to the health care system. However, LDKT is the least common treatment option. Despite growing need manifest by the progressive rise in the United States kidney transplant waiting list to >100,000 candidates, LDKT in the United States has declined from a peak of 6000 in 2004 to current rates of approximately 5500 per year (1). On the basis of such data and surveys supporting positive public perceptions of living donation, a number of recent initiatives are underway to increase awareness of LDKT, including a recent American Society of Transplantation Consensus Statement promoting LDKT as the “best treatment option” for eligible patients with kidney failure (2).

Strategies for increasing LDKT reported in the literature include educational interventions, public campaigns, program efficiencies, and cost mitigation efforts, such as tax policies. Understanding the effect of such interventions is critical before broader adoption, because many are resource intensive. It is also possible that some interventions, although intuitively beneficial, might have little to no effect or even negatively affect donor availability in practice. However, deciphering the existing literature is challenging due to the diversity of study designs and end points. A new article by Barnieh et al. (3) offers a timely advance in understanding the current state of the evidence of strategies designed to increase LDKT rates. The authors performed a scoping review of electronic databases through March of 2016 and identified 26 publications reporting strategies to increase living donation. Prespecified outcomes of interest ranged from numbers of LDKT or donation events to living donor evaluations, potential donor contacts to the transplant center, potential donors identified, persons asked to donate, recipients evaluated, discussion of living donation, stated intent to donate, and consideration of living donation. Of the 26 studies, seven were randomized, controlled trials (RCTs), all assessing educational interventions, with two targeting potential donors and two targeting potential recipients. The remaining studies used quasiexperimental (nonrandomized intervention delivery) and observational designs to examine an array of interventions.

In characterizing the nature of the available evidence, this review reveals that education is the only strategy empirically assessed by RCTs to date. Education about living donation and LDKT is complex, in that comprehensive education involves multiple learners—the transplant candidate, potential living donors, and social support networks—and requires communicating complex information about the risks and benefits of LDKT, living donation, and alternative therapies to these different audiences (4). Results of the identified educational RCTs varied across the outcomes, with only two, both focused on home-based education of transplant candidates and members of their social network, reporting significant increases in LDKT and living donor evaluations. In brief, the “House Calls” program developed by Rodrigue et al. (5) involves delivery of a 60- to 90-minute education session by a trained health educator in the candidate’s home, including family and members of the candidate’s social network. In one RCT enrolling 169 transplant candidates, the LDKT rate in House Calls participants was 52% compared with 30% among those who received clinic-based education. An RCT of a Dutch-based adaptation of home-based education reported a similar effect on LDKT (6), and both trials reported increased donor evaluations. None of the other RCTs of educational interventions, including structured delivery of educational materials, health educator discussions at dialysis centers, and an iPod video intervention, found positive effects on any outcome of interest. Limitations of home-based education include that the costs (and cost-effectiveness) of training and supporting staff to perform the intervention are not yet defined and that logistic issues, such as geography, may challenge the ability of some centers to send staff into the community. Importantly, home-based education is an evidence-based strategy for increasing LDKT access, with notable features including participation not just of the transplant candidate but also chosen members of their social network, personalized focus on an individual transplant candidate, and delivery of the intervention within the community.

The six quasiexperimental and 13 observational studies identified in the scoping review assessed diverse strategies, including programs in education, campaigns, advocacy (training a donor champion), efficiency (web-based screening and creation of interdisciplinary teams), removal of disincentives (tax benefits and leave policies), and creation of kidney paired donation and incompatible transplantation programs. The only quasiexperimental study that identified an increase in LDKT was a structured educational program for potential recipients and their families, although risk of bias was unclear due to missing information. The quality of observational studies was not assessed due to high risk of bias, but five reported significant increases in LDKT, including living donor program promotion, education about preemptive transplantation, use of a “Live Donor Champion,” and laws prohibiting reimbursement for recipients getting transplants in counties that did not adhere to the Declaration of Istanbul.

A key lesson from the scoping review by Barnieh et al. (3) is that high-quality evidence for strategies to increase LDKT is currently limited. So, what are the next steps for practitioners and policymakers to expand LDKT to more patients who can benefit? We and others believe that the strategies that have the potential to improve informed consent and access to LDKT include (1) broader and repeated LDKT education beginning at earlier stages of kidney disease and involving the patient’s social network, (2) removal of disincentives to donation, (3) optimized efficiency in the evaluation of donor candidates, and (4) improving the safety and defensibility of donor selection (Figure 1). However, because transplant programs, nephrology providers, insurers, and policymakers face limited resources, formal evaluations are needed to guide cost-effective investments, at a minimum through quasiexperimental designs and ideally with RCTs, to provide the strongest evidence when possible. Studies must capture LDKT events as a hard outcome of critical importance and incorporate efforts to minimize bias through attention to group comparability, rigorous definitions of the exposure and outcomes, and complete follow-up.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1.

Focal points for future research to define effective strategies for increasing access to living donor kidney transplantation.

Unanswered questions with regard to LDKT educational interventions include how much time and educational content (i.e., “dose”) should be provided at each time point (4). It is also unclear whether the dose should vary over time for patients who have been educated about LDKT and to what extent interventions should be tailored. There are clear disparities in LDKT on the basis of race/ethnicity and other factors, and attention to improve equity for nonwhite patients and those with lower levels of socioeconomic status and health literacy is an important priority. Technology may enable efficient education delivery, but to date, there is little definitive evidence showing whether e-learning, telehealth, or telephone-based LDKT education programs are as effective as programs that deliver education with an in-person educator. Dissemination studies of evidence-based programs are also needed to determine whether effects are maintained when programs are scaled to reach large numbers of patients and to identify additional or unexpected barriers that may arise with broader implementation.

Although removal of disincentives is widely accepted as necessary to improve equity in donation opportunities and access to LDKT, there is a striking lack of evidence for programs directed at achieving financial neutrality. It is well documented that donors incur many types of direct and indirect costs in the donation process, including for travel, medications, lost income, and dependent care; insurance barriers after donation have also been reported (7). The quasiexperimental studies to remove disincentives to LDKT identified in the scoping review did not significantly increase LDKT, but these studies mainly examined primary tax credits at the state-wide level, not at the individual level. Although some endorse trials of financial incentives as the most potentially impactful approach to increase LDKT, testing of incentives in the United States would require amendment of the National Organ Transplant Act (NOTA), which prohibits organ exchange for “valuable consideration” (8). Furthermore, given the substantial opportunities to address uncompensated costs incurred by all donors, we believe that efforts to scientifically evaluate removal of disincentives are the current priority. The NOTA does not prohibit “reasonable payments associated with the expenses of travel, housing, and lost wages incurred by the donor,” and a new RCT assessing the effect of reimbursement of lost wages, supported by the National Living Donor Assistance Act, was announced in December of 2016 (8).

Living donor evaluation is a complex process that begins when someone considering donation contacts a transplant program and progresses through an array of testing, examinations, and visits with program staff. Not surprisingly, some donor candidates find that it takes too long to complete their evaluation, and recipients may need to start dialysis before the donor candidate completes evaluation. A quasiexperimental study in the scoping review evaluated a web-based intervention for self-screening by potential donors and reported a significant increase in the number of contacts to the transplant center; the study also reported increased donor evaluations and LDKT but did not note statistical significance. More work is needed to define efficiency in the donor evaluation and develop evidence-based standards to address modifiable process delays (9).

In recent years, a growing body of evidence is emerging to quantify and refine estimates of the potential risks of living donation, such as a new tool for estimating the projected 15-year and lifetime risks of kidney failure (in the absence of donation) according to the donor candidate demographic and health profile (10). More work is needed to validate and improve the precision of such tools and incorporate donation-attributable risks, but importantly, methods for communicating risk information in this population are largely unstudied. Although interventions to improve transparent risk communication and long-term donor safety are not primarily directed at increasing LDKT, such efforts are essential for supporting LDKT within a defensible system of practice and informing evidence-based education and donor screening strategies.

LDKT is an important treatment option for kidney failure that can be performed safely to benefit many patients and society but has not increased in response to the growing organ shortage. Empirical studies of approaches to support and increase LDKT, including formal evaluations of education, removal of disincentives, practice efficiency, and risk evaluation and communication, incorporating assessment of hard outcomes and associated costs, are feasible and necessary to advance the field from intuition to evidence-based effective practices. Robust efforts to address current knowledge gaps are a vital step in increasing opportunities for more healthy, willing persons to give the gift of life to patients in needs.

• Copyright © 2017 by the American Society of Nephrology