INTRODUCTION Live kidney donors (LKDs) of African ancestry have a higher risk for developing end-stage kidney disease (ESKD) than demographically matched healthy nondonors.1 Retrospective data from the general population reveal that having 2 apolipoprotein L1 gene (APOL1) kidney-risk variants (KRVs) (ie, G1G1, G2G2, or G1G2) contributes to this risk.2 Two APOL1 KRVs vary in frequency around the world with approximately 11%–32% in African Americans (AAs), sub-Saharan Africans, and Western Africans, 5%–22% in Afro-Brazilians, Afro-Caribbeans, or Black Hispanics/Latinx, and approximately 0% in European Americans.3 APOL1 genetic testing is available, and in the absence of prospective data, the role of APOL1 genotyping in LKD candidate selection remains uncertain. Recent survey data reported wide variation in genetic testing practices and clinical use of results during the donor selection process.4 There are several ethical issues concerning the use of genetic testing to determine donor eligibility, which are central to development of policy around APOL1 genetic testing, release of results, and counseling.5 The National Institutes of Health initiated the prospective multicenter U01 “APOL1 Long-term Kidney Transplantation Outcomes Network” (APOLLO) to help understand the impact of APOL1 KRVs on long-term kidney function of donors and recipient outcomes.6 As the transplant community awaits the results of definitive research, the American Society of Transplantation’s Living Donor Community of Practice commissioned a workgroup to develop interim recommendations for APOL1 genetic testing. The workgroup, comprising a transplant nephrologist, a transplant surgeon, a nephrologist with expertise in genetics, a former LKD of African ancestry, a general nephrologist, and a bioethicist, produced this report. APOL1 and Native Kidney Disease The discovery of the association of APOL1 KRVs and chronic kidney disease (CKD) revealed that unrelated forms of nondiabetic nephropathy comprise a spectrum of APOL1-related diseases, including hypertension-attributed nephropathy, focal segmental glomerulosclerosis, HIV-associated nephropathy, and severe lupus nephritis.7 However, most people with 2 APOL1 KRVs do not develop ESKD. Second hits or modifying factors such as viral infections are required to initiate kidney disease.8 APOL1 and Deceased Donor Kidney Transplantation Kidneys transplanted from deceased donors with 2 APOL1 KRVs are associated with premature allograft failure and a ~2-fold increased risk of allograft loss compared with kidneys from donors with 1 or 0 APOL1 KRVs.9 Similar to native kidney disease, a second insult may be required to develop allograft failure after transplanting kidneys from AA deceased donors carrying 2 APOL1 KRVs. APOL1 and Former Living Kidney Donors A cohort of 136 AA LKDs with postdonation follow-up information was stratified by APOL1 genotype.10 Donors with 2 APOL1 KRVs had lower predonation and postdonation estimated glomerular filtration rates (eGFRs) and faster annual declines in eGFR than donors with 0 or 1 KRV (1.19 versus 0.4 mL/min/1.73 m2 per y; P = 0.02). Of 19 donors carrying 2 APOL1 KRVs, 2 (11%) developed ESKD. However, the 11% frequency of ESKD in LKDs with 2 APOL1 KRVs in this study may not be an accurate estimate because of the small sample size and inability to genotype all eligible participants. APOL1 and Risk of Kidney Disease in Young, Healthy Potential Donors A cohort of 3438 individuals aged 18–30 y who were deemed medically suitable to donate was retrospectively assessed for development of CKD stage 3 or higher after 25 y.11 Among the 18-y olds, the 25-y projected CKD risk was higher in AAs than Whites and varied by sex. The risk of CKD increased further among those with 2 APOL1 KRVs. The risk of CKD was much greater for individuals with 2 APOL1 KRVs who presented with relative contraindications for donation, including impaired fasting blood sugar, body mass index >30 kg/m2, eGFR 90–99 mL/min/1.73 m2, smoking, and a family history of hypertension and diabetes. Based on the risk calculator in this article, an 18-y-old male individual with 2 APOL1 KRVs and no other risk factors was anticipated to have an equivalent risk of CKD as a 30-y-old AA female individual with a family history of diabetes and 0 APOL1 KRVs. The risk of CKD associated with APOL1 KRVs was similar to some of the other risk factors that routinely appear during donor evaluation and generally do not raise similar concerns among transplant professionals. Providers’, AA LKDs’, and Community Members’ Attitudes About APOL1 Testing In a recent survey of transplant nephrologists, transplant surgeons, and community nephrologists, most physicians believed that all potential AA LKDs should be informed about the option of APOL1 testing.12 Similarly, AA LKDs and members of the public recommended that APOL1 testing be routinely offered to donors in clinical care to foster informed decision making about donation.13,14 Half of the surveyed physicians would not proceed or strongly recommend against donation in potential LKDs carrying 2 APOL1 KRVs. However, both AA LKDs and members of the public opposed it as such a policy would violate donor autonomy.13,15 Instead, most community members preferred that the physician and potential LKD together make a shared decision about donation.14 Considering the Available Information, the AST LDCoP APOL1 Workgroup Proposes the Following Guidelines: 1. Who should be educated, by whom, and when? All potential LKD candidates who self-report African ancestry (including AA, Afro-Caribbeans, and Hispanic/Latinx Blacks, Africans) should be informed about the APOL1 gene and risk of ESKD. Although individuals from North Africa and those with mixed ancestry are less likely to carry 2 APOL1 KRVs, they should still be informed about APOL1 and the lower likelihood of carrying 2 APOL1 KRVs. Providers should ask potential donors about their ancestry and ethnic identity rather than rely on their own perceptions or medical records. Counseling can be provided by a transplant team member under the guidance of a transplant nephrologist early in the evaluation process. 2. Who should be tested? AA LKD candidates with known independent risk factors for the development of ESKD such as young age (<44 y), male gender, history of smoking, obesity (body mass index >30 kg/m2), hypertension, low to normal eGFR (90–99 mL/min/1.73 m2), and a family history of ESKD, hypertension, or diabetes in a first-degree relative may be considered for testing. Among donor candidates with 2 or more of these risk factors, the absence of 2 APOL1 KRVs has not been reported to mitigate their future risk of ESKD; such individuals should be counseled about their elevated risk of ESKD before genetic testing.16 For LKD candidates who want to pursue donation after adequate discussion and their risk of ESKD is deemed acceptable by the transplant center, genetic testing for APOL1 KRVs may be offered for further risk stratification. Genetic testing should only be offered after appropriate counseling. LKDs who wish to donate, regardless of their genetic test result, should be allowed to proceed if their risk of ESKD does not exceed the acceptable threshold set by their transplant program. 3. When should testing be offered? If genetic testing is deemed appropriate, it should only be offered to candidates who have passed preliminary medical and psychosocial evaluation, preferably not during the initial screening. This approach is less expensive and provides physicians with the chance to counsel potential LKDs when they have a clinical or laboratory abnormality that may preclude them from donation, regardless of genotype. APOL1 testing may be performed before HLA typing, crossmatching, or computed tomography scanning, because these tests are less likely to rule out donors. 4. What topics should be covered in counseling? Transplant programs should address the pros and cons of APOL1 genetic testing before ordering the test. They should acknowledge the lack of robust data on the postdonation risk of ESKD in potential LKDs carrying 2 APOL1 KRVs and discuss the small study reporting an 11% risk of ESKD 12 y after donation. Programs should also inform potential LKDs that not all individuals carrying 2 APOL1 KRVs develop kidney disease and “second-hits” are required for deterioration in kidney function. Currently, the nature of second hits beyond certain viral infections is unknown. Transplant programs should inform LKD candidates about the national APOLLO study so that candidates can stay apprized of the study results in their decision to donate. The results of the APOLLO study will improve our understanding of the risks involved in donating among individuals with 2 APOL1 KRVs. Other topics of discussion should include, but are not limited to, the lack of specific treatments to prevent APOL1-associated kidney disease, the risk to themselves and to the potential recipient of not donating, and the possibility of psychological distress upon learning that potential LKDs have 2 APOL1 KRVs. Finally, counseling should discuss the role of the Genetic Information Nondiscrimination Act in protecting donors from employer and insurance-based discrimination. Counseling should be offered by a genetic counselor, nephrologist, or transplant team member trained to deliver counseling about APOL1 before donation and to deliver counseling with results thereafter. 5. How should positive test results be approached? The workgroup supports shared decision making between the transplant team and potential LKDs about donating in the context of APOL1 KRVs. Shared decision making entails 2-way communication between donors expressing their preferences and values and providers disclosing information about the procedure, its risks, benefits, and alternatives, out of respect for donor autonomy. As with other single risk factors, the isolated finding of 2 APOL1 KRVs should not be enough to automatically exclude the donor candidate. The presence of ≥2 baseline risk factors for future ESKD (including 2 APOL1 KRVs and other risk factors listed above) should be considered in the informed consent discussion.11 However, the team that recognizes the donor-recipient relationship may influence the donor’s decision. Some potential LKDs may wish to donate despite being informed of their increased future risk for ESKD; other LKDs may want the physician to decide for them. In either case, the risk of ESKD in the donor should be lower than the established acceptable threshold for the transplant center. 6. Should recipients be informed of the living donor’s genotype? To protect the donor’s privacy, the transplant team should not reveal the donor candidate’s APOL1 genotype to the recipient. Donors should decide whether they wish to discuss their genetic test results with the recipient and with family members. If the LKD candidate requests and the potential recipient agrees, transplant programs can jointly discuss genotype results and their implications with the pair. 7. Should a donor with 2 APOL1 KRVs be discouraged to donate because of concerns about recipient outcomes? Currently, no data exist on the impact of the living donor APOL1 genotype on recipient outcomes. The currently available data suggest that transplantation from a LKD, even with 2 APOL1 KRVs, is better for the recipient’s health than remaining on dialysis or waiting to receive a transplant from a deceased donor. 8. Who should bear the cost of APOL1 genotyping? Testing costs range from $300 to $500 and should be covered as a part of the Organ Acquisition Cost by the transplant center. SUMMARY AND FUTURE DIRECTIONS Results of the NIH-funded APOLLO study will not be available to inform clinical practice for several years. Until then, APOL1 genetic testing may supplement the already comprehensive donor evaluation process, as needed, for risk stratification and may be ordered after appropriate counseling has been provided. The decision to donate, in the case of a high-risk genotype, should be handled through shared decision making. Such an approach resonates with LKDs and community members because it addresses matters of consent and donor autonomy. These recommendations are intended to guide transplant centers in developing their own policies around APOL1 genetic testing and donor acceptance criteria. While the transplant community must await new findings and continue to improve its understanding of donor ESKD risk, there should not be a rush to pronounce judgment on the significance of APOL1 KRVs in living donors until firm data are available. ACKNOWLEDGMENTs This article is a work product of the American Society of Transplantation’s Live Donor Community of Practice.
We investigated kidney transplant recipients' self-reported levels of exercise and fluid intake. We also examined attitudes about, barriers to undertaking, and strategies used to initiate and maintain adequate self-care for fluid intake, exercise and dietary practices.A qualitative approach was used and supplemented by quantitative data to examine self-care among kidney transplant recipients (n = 82), including a semi-structured interview and survey of physical activity.One-third of patients (33%) reported drinking the recommended 3 L of fluid each day. However, the majority (60%) reported not receiving this or any specific fluid intake recommendation. Twenty percent reported engaging in moderate to regular physical activity while 78% were sedentary. However, many reported that clinicians did not specify the amount of exercise (39%) or did not discuss exercise (15%). Attitudes towards fluid intake, exercise and maintaining a low-salt diet were mostly positive; patients expressed relatively more negative attitudes towards maintaining a low-cholesterol diet. Major barriers to fluid intake were not feeling thirsty, difficulty breaking the habit of limiting fluid intake formed while on dialysis, feeling full and limited access to fluids. Patients devised creative strategies to initiate and maintain appropriate hydration, physical activity and dietary levels, including intentionally drinking when not thirsty, modifying the environment, tracking intake and relying on social supports.Few kidney recipients practiced optimal self-care for fluid intake or physical activity. Most patients encountered barriers to self-care that should be ameliorated to assist patients with managing their transplant. Understanding barriers and strategies is essential for developing educational interventions.
Adult-to-adult living donor liver transplantation (LDLT) is a complex procedure that poses serious health risks to and provides no direct health benefit for the donor. Because of this uneven risk-benefit ratio, ensuring donor autonomy through informed consent is critical. To assess the current knowledge pertaining to informed consent for LDLT, we conducted a systematic review of the empirical literature on donors' decision-making process, comprehension about risks and outcomes, and information needs for LDLT. Of the 1423 identified articles, 24 met final review criteria, representing the perspective of approximately 2789 potential and actual donors. As donors' decisions to donate often occur before evaluation, they often make uninformed decisions. The review found that 88% to 95% of donors reported understanding information clinicians disclosed about risks and benefits. However, donors reported unmet information needs, knowledge gaps regarding risks, and unanticipated complications. Few donors reported feeling pressure to donate. Most studies were limited by cultural differences, small sample sizes, inconsistent measures, and poor methodological approaches. This systematic review suggests that informed consent for LDLT is sub-optimal as donors do not adequately appreciate disclosed information during the informed consent process, despite United Network for Organ Sharing/CMS regulations requiring formal psychological evaluation of donor candidates. Interventions are needed to improve donor-clinician communication during the LDLT informed consent process such as through the use of comprehension assessment tools and e-health educational tools that leverage adult learning theory to effectively convey LDLT outcome data.
The disclosure of prognosis to terminally ill patients has emerged as a recent concern given greater demands for patient involvement in medical decision-making in the United States. As part of the informed consent process, American physicians are legally and ethically obligated to provide information to such patients about the risks, benefits, and alternatives of all available treatment options including the use of experimental therapies. Although not legally required, the disclosure of a terminal prognosis is ethically justified because it upholds the principle of self-determination and enables patients to make treatment decisions consistent with their life goals. To understand oncologists' attitudes about disclosing prognostic information to cancer patients with advanced disease, we interviewed fourteen oncologists and conducted one focus group of medical fellows. Although oncologists reported to disclose prognosis in terms of cancer not being curable, they tend to avoid using percentages to convey prognosis. Oncologists' reported reluctance to disclosing prognosis was conveyed through the use of metaphors depicting the perceived violent impact of such information on patients. Oncologists' reluctance to disclose prognosis and preserve patient hope are held in check by their need to ensure that patients have 'realistic expectations' about therapy. We discuss these data in light of the cultural, ethical, and legal dimensions of prognosis disclosure, patient hope and the doctor-patient relationship, and recommend ways to enhance the communication process.
Shortening and skipping hemodialysis treatments occur commonly and are associated with inadequate dialysis and increased mortality. These behaviors are also frequently equated with patient noncompliance. The prevalence and demographic correlates of shortening and skipping treatments have been studied extensively. However, less is known about the reasons for shortening and skipping treatments and whether patient characteristics correlate with specific reasons. Understanding the relationship between reasons and patient characteristics is essential for determining whether patient subgroups are at a disadvantage in achieving optimal dialysis and may help guide future interventions. Semistructured interviews were conducted with 168 selected patients who shortened or skipped treatments. A variety of reasons were responsible for shortening and skipping hemodialysis treatments. Content analysis of patient responses revealed five categories of reasons for shortening and skipping, including medical problems, technical problems, life tasks, transportation, and patient decisions. The most common reasons for shortening were medical problems (38%) and life tasks (24%), while the most common reasons for skipping were life tasks (33%) and transportation (22%). Furthermore, patient subgroups differed in the reasons for shortening and skipping. After multivariate adjustment for patient characteristics, technical problems were more common among women. Life tasks were more common among men, younger patients, and patients with hypertension. Transportation problems were more common among African Americans. Interventions to optimize hemodialysis treatment should identify and target patient-specific reasons for shortening and skipping and not assume noncompliance.
Abstract Background Despite evidence that antibiotics may not be necessary to treat acute uncomplicated diverticulitis, they remain the mainstay of treatment in the United States. A randomized controlled trial evaluating antibiotic effectiveness could accelerate implementation of an antibiotic-free treatment strategy, but patients may be unwilling to participate. Objective This study aims to assess patients’ attitudes regarding participation in a randomized trial of antibiotics versus placebo for acute diverticulitis, including willingness to participate. Design This is a mixed-methods study with qualitative and descriptive methods. Settings Interviews were conducted in a quaternary care emergency department and surveys were administered virtually through a web-based portal. Patients Patients with either current or previous acute uncomplicated diverticulitis participated. Interventions Patients underwent semi-structured interviews or completed a web-based survey. Main Outcome measures Rates of willingness to participate in a randomized controlled trial was measured. Salient factors related to healthcare decision-making were also identified and analyzed. Results Thirteen patients completed an interview. Reasons to participate included a desire to help others or contribute to scientific knowledge. Doubts about the efficacy of observation as a treatment method were the main barrier to participation. In a survey of 218 subjects, 62% of respondents reported willingness to participate in a randomized clinical trial. “What my doctor thinks,” followed by “What I’ve experienced in the past” were the most important decision-making factors. Limitations There is possible selection bias inherent to using a study to evaluate willingness to participate in a study. Also, the population sampled was disproportionately White compared to the population affected by diverticulitis. Conclusions Patients with acute uncomplicated diverticulitis maintain complex and varying perceptions of the use of antibiotics. Most surveyed patients would be willing to participate in a trial of antibiotics versus placebo. Our findings support a trial’s feasibility and facilitate an informed approach to recruitment and consent.
Rationale & ObjectiveOlder adults with advanced chronic kidney disease (CKD) face difficult decisions about dialysis initiation. Although shared decision making (SDM) can help align patient preferences and values with treatment options, the extent to which older patients with CKD experience SDM remains unknown.Study DesignA cross-sectional analysis of patient surveys examining decisional readiness, treatment options education, care partner support, and SDM.Setting & ParticipantsAdults aged 70 years or older from Boston, Chicago, San Diego, or Portland (Maine) with nondialysis advanced CKD.PredictorsDecisional readiness factors, treatment options education, and care partner support.OutcomesPrimary: SDM measured by the 9-item Shared Decision Making Questionnaire (SDM-Q-9) instrument, with higher scores reflecting greater SDM. Exploratory: Factors associated with SDM.Analytical ApproachWe used multivariable linear regression models to examine the associations between SDM and predictors, controlling for demographic and health factors.ResultsAmong 350 participants, mean age was 78 ± 6 years, 58% were male, 13% identified as Black, and 48% had diabetes. Mean SDM-Q-9 score was 52 ± 28. SDM item agreement ranged from 41% of participants agreeing that "my doctor and I selected a treatment option together" to 73% agreeing that "my doctor told me that there are different options for treating my medical condition." In multivariable analysis adjusted for demographic characteristics, lower estimated glomerular filtration rate, and diabetes, being "well informed" and "very well informed" about kidney treatment options, having higher decisional certainty, and attendance at a kidney treatment options class were independently associated with higher SDM-Q-9 scores.LimitationsThe cross-sectional study design limits the ability to make temporal associations between SDM and the predictors.ConclusionsMany older patients with CKD do not experience SDM when making dialysis decisions, emphasizing the need for greater access to and delivery of education for individuals with advanced CKD. Older adults with advanced chronic kidney disease (CKD) face difficult decisions about dialysis initiation. Although shared decision making (SDM) can help align patient preferences and values with treatment options, the extent to which older patients with CKD experience SDM remains unknown. A cross-sectional analysis of patient surveys examining decisional readiness, treatment options education, care partner support, and SDM. Adults aged 70 years or older from Boston, Chicago, San Diego, or Portland (Maine) with nondialysis advanced CKD. Decisional readiness factors, treatment options education, and care partner support. Primary: SDM measured by the 9-item Shared Decision Making Questionnaire (SDM-Q-9) instrument, with higher scores reflecting greater SDM. Exploratory: Factors associated with SDM. We used multivariable linear regression models to examine the associations between SDM and predictors, controlling for demographic and health factors. Among 350 participants, mean age was 78 ± 6 years, 58% were male, 13% identified as Black, and 48% had diabetes. Mean SDM-Q-9 score was 52 ± 28. SDM item agreement ranged from 41% of participants agreeing that "my doctor and I selected a treatment option together" to 73% agreeing that "my doctor told me that there are different options for treating my medical condition." In multivariable analysis adjusted for demographic characteristics, lower estimated glomerular filtration rate, and diabetes, being "well informed" and "very well informed" about kidney treatment options, having higher decisional certainty, and attendance at a kidney treatment options class were independently associated with higher SDM-Q-9 scores. The cross-sectional study design limits the ability to make temporal associations between SDM and the predictors. Many older patients with CKD do not experience SDM when making dialysis decisions, emphasizing the need for greater access to and delivery of education for individuals with advanced CKD.
