Removing the physician from the equation: Patient-controlled, home-based therapeutic drug self-monitoring of tacrolimus.

The dosing of tacrolimus, which forms the backbone of immunosuppressive therapy after kidney transplantation, is complex. This is due to its variable pharmacokinetics (both between and within individual patients), narrow therapeutic index, and the severe consequences of over- and underexposure, which may cause toxicity and rejection, respectively. Tacrolimus is, therefore, routinely dosed by means of therapeutic drug monitoring (TDM). TDM is performed for as long as the transplant functions and frequent and often lifelong sampling is therefore the rule. This puts a significant burden on patients and transplant professionals and is associated with high healthcare-associated costs. Furthermore, by its very nature, TDM is reactive and has no predictive power. Finally, the current practice of TDM does not foresee in an active role for patients themselves. Rather, the physician or pharmacist prescribes the next tacrolimus dose after obtaining the concentration measurement test results. In this article, we propose a strategy of patient-controlled, home-based, self-TDM of the immunosuppressant tacrolimus after transplantation. We argue that with the combined use of population tacrolimus pharmacokinetic models, home-based sampling by means of dried blood spotting and implementation of telemedicine, this may become a feasible approach in the near future.

Clinical Translation of Bio-Artificial Pancreas Therapies: Ethical, Legal and Psychosocial Interdisciplinary Considerations and Key Recommendations.

The field of regenerative medicine offers potential therapies for Type 1 Diabetes, whereby metabolically active cellular components are combined with synthetic medical devices. These therapies are sometimes referred to as "bioartificial pancreases." For these emerging and rapidly developing therapies to be clinically translated to patients, researchers must overcome not just scientific hurdles, but also navigate complex legal, ethical and psychosocial issues. In this article, we first provide an introductory overview of the key legal, ethical and psychosocial considerations identified in the existing literature and identify areas where research is currently lacking. We then highlight two principal areas of concern in which these discrete disciplines significantly overlap: 1) individual autonomy and 2) access and equality. Using the example of beta-cell provenance, we demonstrate how, by harnessing an interdisciplinary approach we can address these key areas of concern. Moreover, we provide practical recommendations to researchers, clinicians, and policymakers which will help to facilitate the clinical translation of this cutting-edge technology for Type 1 Diabetes patients. Finally, we emphasize the importance of exploring patient perspectives to ensure their responsible and acceptable translation from bench to body.

Counselling on Conceiving: Attitudes and Factors Influencing Advice of Professionals in Transplantation.

Pregnancy after kidney transplantation (KT) conveys risks of adverse pregnancy outcomes (APO). Little is known about performance of pre-pregnancy counselling after KT. This study investigated perceptions of risk, attitudes towards pregnancy and factors influencing advice given at pre-pregnancy counselling after KT. A web-based vignette survey was conducted among nephrologists and gynaecologists between March 2020 and March 2021, consisting of five vignettes containing known risk factors for APO and general questions on pre-pregnancy counselling after KT. Per vignette, attitudes towards pregnancy and estimation of outcomes were examined. In total 52 nephrologists and 25 gynaecologists participated, 56% from university hospitals. One third had no experience with pregnancy after KT. All gave positive pregnancy advice in the vignette with ideal circumstances (V1), versus 83% in V2 (proteinuria), 81% in V3 (hypertension), 71% in V4 (eGFR 40 ml/min/1.73 m2). Only 2% was positive in V5 (worst-case scenario). Chance of preeclampsia was underestimated by 89% in V1. 63% and 98% overestimated risk for graft loss in V4 and V5. Professionals often incorrectly estimated risk of APO after KT. As experience with pregnancy after KT was limited among professionals, patients should be referred to specialised centres for multidisciplinary pre-pregnancy counselling to build experience and increase consistency in given advice.

Twenty Years of Unspecified Kidney Donation: Unspecified Donors Looking Back on Their Donation Experiences.

The Netherlands was the first European country to implement unspecified kidney donation in 2000. This qualitative study aimed to evaluate the experiences of unspecified kidney donors (UKDs) in our transplant institute to improve the care for this valuable group of donors. We conducted semi-structured interviews with 106 UKDs who donated between 2000-2016 (response rate 84%). Interviews were audio-recorded, transcribed verbatim and independently coded by 2 researchers in NVivo using thematic analysis. The following 14 themes reflecting donor experiences were found: Satisfaction with donation; Support from social network; Interpersonal stress; Complaints about hospital care; Uncertainty about donor approval; Life on hold between approval and actual donation; Donation requires perseverance and commitment; Recovery took longer than expected; Normalization of the donation; Becoming an advocate for living kidney donation; Satisfaction with anonymity; Ongoing curiosity about outcome or recipient; Importance of anonymous communication; Anonymity is not watertight. The data reinforced that unspecified kidney donation is a positive experience for donors and that they were generally satisfied with the procedures. Most important complaints about the procedure concerned the length of the assessment procedure and the lack of acknowledgment for UKDs from both their recipients and health professionals. Suggestions are made to address the needs of UKDs.

Relinquishing Anonymity in Living Donor Kidney Transplantation: Lessons Learned From the UK Policy for Anonymous Donors.

Anonymous living donor kidney transplantation (LDKT) is performed in many countries and policies on anonymity differ. The UK is the only European country with a conditional policy, allowing pairs to break anonymity post-transplant. There is little evidence on how contact after anonymous LDKT is experienced. In this cross-sectional study participants who donated or received a kidney through non-directed altruistic kidney donation or within the UK living kidney sharing scheme completed a questionnaire on their experiences with and attitudes towards anonymity. Non-parametric statistics were used to analyse the data. 207 recipients and 354 donors participated. Anonymity was relinquished among 11% of recipients and 8% of donors. Non-anonymous participants were generally content with non-anonymity. They reported positive experiences with contact/meeting the other party. Participants who remained anonymous were content with anonymity, however, 38% would have liked to meet post-transplant. If the other party would like to meet, this number increased to 64%. Although participants agreed with anonymity before surgery, they believe that, if desired, a meeting should be allowed after surgery. UK donors and recipients were satisfied with conditional anonymity and experiences with breaking anonymity were positive. These results support the expansion of conditional anonymity to other countries that allow anonymous LDKT.

Early-Phase Clinical Trials of Bio-Artificial Organ Technology: A Systematic Review of Ethical Issues.

Regenerative medicine has emerged as a novel alternative solution to organ failure which circumvents the issue of organ shortage. In preclinical research settings bio-artificial organs are being developed. It is anticipated that eventually it will be possible to launch first-in-human transplantation trials to test safety and efficacy in human recipients. In early-phase transplantation trials, however, research participants could be exposed to serious risks, such as toxicity, infections and tumorigenesis. So far, there is no ethical guidance for the safe and responsible design and conduct of early-phase clinical trials of bio-artificial organs. Therefore, research ethics review committees will need to look to related adjacent fields of research, including for example cell-based therapy, for guidance. In this systematic review, we examined the literature on early-phase clinical trials in these adjacent fields and undertook a thematic analysis of relevant ethical points to consider for early-phase clinical trials of transplantable bio-artificial organs. Six themes were identified: cell source, risk-benefit assessment, patient selection, trial design, informed consent, and oversight and accountability. Further empirical research is needed to provide insight in patient perspectives, as this may serve as valuable input in determining the conditions for ethically responsible and acceptable early clinical development of bio-artificial organs.

EXPloring attitudes and factors influencing reproductive Choices in kidney Transplant patients (The EXPECT-study).

Pregnancy can have risks after kidney transplantation (KT). This mixed-methods study aimed to identify the percentage of women getting pregnant after KT and explore motives for and against pregnancy together with psychosocial and medical factors involved in decision making. Furthermore, experiences of pregnancy and child-raising were explored. Women who got pregnant after KT were matched with women who had not been pregnant after KT. Semi-structured interviews were conducted, transcribed verbatim and analyzed using directed content analysis. After KT, only 12% of women got pregnant. Eight women with pregnancies after KT were included (P-group) and matched with 12 women who had not been pregnant after KT (NP-group). Women after KT experienced a high threshold to discuss their pregnancy wish with their nephrologist. The nephrologists' advice played an important role in decision-making, but differed between the groups. In the P-group, a desire for autonomy and positive role models were decisive factors in proceeding with their pregnancy wish. In the NP-group, disease burden and risk perception were decisive factors in not proceeding with their pregnancy. Nephrologists need to be proactive in broaching this subject and aware of factors influencing the decision and outcomes. Standardized preconception guidelines on pregnancy counseling are recommended.

Is simplification of immunosuppressive medication a way to promote medication adherence of kidney transplant recipients? Findings from a randomized controlled trial.

After kidney transplantation, a strict immunosuppressive medication regimen is necessary for graft survival. However, nonadherence to medication has been shown to occur early after transplantation and to increase over time. Weaning the recipient off dual therapy onto monotherapy in order to reduce immunosuppressive burden may also be a way to promote adherence, although little is known about the impact of such a regimen on fear of rejection. We performed a cohort study on medication adherence and fear of rejection in a randomized, investigator-driven, open-label, single-centre pilot study. Recipients were randomized at 6-months post-transplant to either continue Tacrolimus and Mycophenolate mofetil (TAC/MMF) or to taper MMF at 6 months and discontinue MMF at 9 months (TAC monotherapy). Recipients completed questionnaires about medication adherence and fear of rejection at 6 and 12-months post-transplantation. Medication adherence was significantly higher in the TAC monotherapy group compared to dual TAC/MMF therapy group (χ2 (1) = 4.582; P = 0.032). We found no difference in fear of rejection between the two groups of recipients (P = 0.887). Simplification of the medication regimen is a potential tool for increasing adherence in clinical practice (Netherlands Trial Register - NL4672).

Implementation of the kidney team at home intervention: Evaluating generalizability, implementation process, and effects.

Research has shown that a home-based educational intervention for patients with chronic kidney disease results in better knowledge and communication, and more living donor kidney transplantations (LDKT). Implementation research in the field of renal care is almost nonexistent. The aims of this study were (1) to demonstrate generalizability, (2) evaluate the implementation process, and (3) to assess the relationship of intervention effects on LDKT-activity. Eight hospitals participated in the project. Patients eligible for all kidney replacement therapies (KRT) were invited to participate. Effect outcomes were KRT-knowledge and KRT-communication, and treatment choice. Feasibility, fidelity, and intervention costs were assessed as part of the process evaluation. Three hundred and thirty-two patients completed the intervention. There was a significant increase in KRT-knowledge and KRT-communication among participants. One hundred and twenty-nine out of 332 patients (39%) had LDKT-activity, which was in line with the results of the clinical trials. Protocol adherence, knowledge, and age were correlated with LDKT-activity. This unique implementation study shows that the results in practice are comparable to the previous trials, and show that the intervention can be implemented, while maintaining quality. Results from the project resulted in the uptake of the intervention in standard care. We urge other countries to investigate the uptake of the intervention.

Global Kidney Exchange: opportunity or exploitation? An ELPAT/ESOT appraisal.

This paper addresses ethical, legal, and psychosocial aspects of Global Kidney Exchange (GKE). Concerns have been raised that GKE violates the nonpayment principle, exploits donors in low- and middle-income countries, and detracts from the aim of self-sufficiency. We review the arguments for and against GKE. We argue that while some concerns about GKE are justified based on the available evidence, others are speculative and do not apply exclusively to GKE but to living donation more generally. We posit that concerns can be mitigated by implementing safeguards, by developing minimum quality criteria and by establishing an international committee that independently monitors and evaluates GKE's procedures and outcomes. Several questions remain however that warrant further clarification. What are the experiences and views of recipients and donors participating in GKE? Who manages the escrow funds that have been put in place for donor and recipients? What procedures and safeguards have been put in place to prevent corruption of these funds? What are the inclusion criteria for participating GKE centers? GKE provides opportunity to promote access to donation and transplantation but can only be conducted with the appropriate safeguards. Patients' and donors' voices are missing in this debate.

Evaluating the feasibility of a nurse-led self-management support intervention for kidney transplant recipients: a pilot study.

BACKGROUND: To support effective self-management after kidney transplantation, a holistic nurse-led self-management support intervention was developed using the Intervention Mapping approach. The primary aim was to evaluate the feasibility, acceptability and fidelity of the intervention for kidney transplant recipients and professionals. The secondary aim was to explore preliminary effects on outcomes. METHODS: A pilot study was conducted in 2015-2017 to evaluate the intervention. Nurse Practitioners (NP) guided recipients in assessing 14 life areas using the Self-Management Web. Participants were supported in developing self-regulation skills which can be applied to self-management of the illness. Strategies included goal setting, action planning, and promotion of motivation and self-efficacy. Adult recipients from an outpatient clinic of a Dutch University Hospital who underwent their transplant at least 1 month ago, were invited to participate. NPs, nephrologists and recipients were interviewed to assess feasibility, fidelity and implementation experience. Consultations were videoed and analysed to assess fidelity. To assess the preliminary effects, the intervention group completed baseline (T0) and follow-up (T1) questionnaires on self-management behavior, self-efficacy, quality of life and quality of care. A historical control group of kidney transplant recipients completed the same questionnaires at T1. RESULTS: Twenty-seven recipients agreed to participate in the intervention group, of which 24 completed the intervention and 16 completed baseline and follow-up surveys. The control group consisted of 33 recipients. Professionals and recipients appraised the open, holistic focus of the intervention as a welcome addition to standard care and felt that this helped to build a relationship of trust. Recipients also felt they became more competent in problem-solving skills. The within-group analysis showed no significant increase in patients' self-management skills. The between-groups analysis showed significantly higher medication adherence among the intervention group (P = 0.03; G = 0.81). The within-groups analysis showed a significantly higher perceived quality of care (P = 0.02) in the intervention group. CONCLUSION: This holistic nurse-led self-management support intervention was found to be feasible and acceptable by professionals and recipients alike. This pilot had a small sample therefore further research is needed into the potential effects on self-management behavior and well-being of transplant recipients. ISRCTN Trial Registry: ISRCTN15057632 (registered retrospectively on 20-07-2018).

Donor and Recipient Perspectives on Anonymity in Kidney Donation From Live Donors: A Multicenter Survey Study.

BACKGROUND: Maintaining anonymity is a requirement in the Netherlands and Sweden for kidney donation from live donors in the context of nondirected (or unspecified) and paired exchange (or specified indirect) donation. Despite this policy, some donors and recipients express the desire to know one another. Little empirical evidence informs the debate on anonymity. This study explored the experiences, preferences, and attitudes of donors and recipients toward anonymity. STUDY DESIGN: Retrospective observational multicenter study using both qualitative and quantitative methods. SETTING & PARTICIPANTS: 414 participants from Dutch and Swedish transplantation centers who received or donated a kidney anonymously (nondirected or paired exchange) completed a questionnaire about anonymity. Participation was a median of 31 months after surgery. FACTORS: Country of residence, donor/recipient status, transplant type, time since surgery. OUTCOMES: Experiences, preferences, and attitudes toward anonymity. RESULTS: Most participants were satisfied with their experience of anonymity before and after surgery. A minority would have liked to have met the other party before (donors, 7%; recipients, 15%) or after (donors, 22%; recipients, 31%) surgery. Significantly more recipients than donors wanted to meet the other party. Most study participants were open to meeting the other party if the desire was mutual (donors, 58%; recipients, 60%). Donors agree significantly more with the principle of anonymity before and after surgery than recipients. Donors and recipients thought that if both parties agreed, it should be permissible to meet before or after surgery. There were few associations between country or time since surgery and experiences or attitudes. The pros and cons of anonymity reported by participants were clustered into relational and emotional, ethical, and practical and logistical domains. LIMITATIONS: The relatively low response rate of recipients may have reduced generalizability. Recall bias was possible given the time lag between transplantation and data collection. CONCLUSIONS: This exploratory study illustrated that although donors and recipients were usually satisfied with anonymity, the majority viewed a strict policy on anonymity as unnecessary. These results may inform policy and education on anonymity.

The ELPAT living organ donor Psychosocial Assessment Tool (EPAT): from 'what' to 'how' of psychosocial screening - a pilot study.

Thorough psychosocial screening of donor candidates is required in order to minimize potential negative consequences and to strive for optimal safety within living donation programmes. We aimed to develop an evidence-based tool to standardize the psychosocial screening process. Key concepts of psychosocial screening were used to structure our tool: motivation and decision-making, personal resources, psychopathology, social resources, ethical and legal factors and information and risk processing. We (i) discussed how each item per concept could be measured, (ii) reviewed and rated available validated tools, (iii) where necessary developed new items, (iv) assessed content validity and (v) pilot-tested the new items. The resulting ELPAT living organ donor Psychosocial Assessment Tool (EPAT) consists of a selection of validated questionnaires (28 items in total), a semi-structured interview (43 questions) and a Red Flag Checklist. We outline optimal procedures and conditions for implementing this tool. The EPAT and user manual are available from the authors. Use of this tool will standardize the psychosocial screening procedure ensuring that no psychosocial issues are overlooked and ensure that comparable selection criteria are used and facilitate generation of comparable psychosocial data on living donor candidates.

"What if this is my chance to save my life?" A semistructured interview study on the motives and experiences of end-stage renal disease patients who engaged in public solicitation of a living kidney donor.

The increase in patients using public solicitation (PS) to find a living kidney donor has generated a debate about the ethical complexities of PS. To investigate why patients engaged in PS and what they experienced during PS, we conducted semistructured interviews with 20 Dutch patients with end-stage renal disease who had publicly solicited a living donor. Transcripts were thematically analyzed. We identified ten themes on patients' considerations preceding PS: cautiousness in discussing living donation within social network; reluctance to accept a kidney from loved ones; rejection/withdrawal of related donor candidates; moral objections to paid donation; the ease of social media; encouraged by others; ends justifying the means; despair and urge to take action; public disclosure of vulnerability; fear of being (perceived to be) selfish. We identified nine themes on patients' experiences: positive emotions and support generated by action; genuine and ulterior motives for donation; patients acting as educators and screeners; time- and energy-consuming process; emotionally taxing process; positive interactions with donor candidates; feeling of dependency and obligation; limited cooperation from health professionals; demands a proactive attitude and media strategy. These results can inform and complement (existing) policies on PS and provide content for education of patients who are considering PS.

Self-management challenges and support needs among kidney transplant recipients: A qualitative study.

AIMS: This study investigated self-management challenges and support needs experienced by kidney transplant recipients. BACKGROUND: After kidney transplantation, recipients are expected to take an active role in self-management. However, evidence suggests that nurses experience difficulties operationalizing self-management support. Greater insight into the recipients' perspective could help to improve the adequacy and efficacy of nurse-led self-management support. DESIGN: A cross-sectional qualitative study. METHODS: Focus groups and individual interviews were carried out with kidney transplant recipients treated in a Dutch university hospital. Directed content analysis (DCA) was used. RESULTS: Forty-one kidney transplant recipients participated. Challenges after transplantation included becoming an expert patient, adjusting daily life activities, dealing with medical regimen, forming relationships with nurses, dealing with social consequences, dealing with emotions related to transplantation and the donor and improving self-image. To be able to deal with these challenges, participants wished to receive disease specific knowledge and instruction, share personal experiences with fellow patients, share and discuss not only medical but also emotional and social issues with nurses and wanted to be encouraged through positive feedback. "One-size fits all" education was considered insufficient in meeting their needs. CONCLUSIONS: After kidney transplantation, recipients experienced various challenges in dealing with the medical, emotional and social tasks. Current support from nurses overlooked recipients' emotional and social support needs. Nurses need adequate tools and training to be able to meet recipients' self-management support needs.

Toward a conditional approach to anonymity? An explorative multicenter longitudinal study among anonymous living kidney donors and recipients.

Anonymity between living donors and recipients is a topic of discussion among transplant professionals. This longitudinal study explored living kidney donors' and patients' perspectives on anonymity. Prior to surgery (T0) and 3 months afterward (T1), participants in unspecified or specified indirect donation programs completed a questionnaire on their experiences with and attitudes toward anonymity as well as demographic and medical characteristics. Nonparametric tests were used to assess group differences and associations. Participants were content with anonymity at T0 and T1. Fourteen and 23% wanted to meet at T0 and T1, respectively. If the other party expressed the wish to meet, 50% (T0) and 55% (T1) would be willing to meet. Most participants agreed that meeting should be allowed if both parties agree. Attitude toward anonymity did not differ between donors/recipients, nor between T0/T1 and unspecified/specified indirect donation programs. This study showed that most donors and recipients who participated in anonymous donation schemes are in favor of a conditional approach to anonymity. Guidelines on how to revoke anonymity if both parties agree are needed and should include education about pros and cons of (non-) anonymity and a logistical plan on how, when, where, and by whom anonymity should be revoked.

Early home-based group education to support informed decision-making among patients with end-stage renal disease: a multi-centre randomized controlled trial.

BACKGROUND: The aim was to test the effectiveness of early home-based group education on knowledge and communication about renal replacement therapy (RRT). METHODS: We conducted a randomized controlled trial using a cross-over design among 80 end-stage renal disease (ESRD) patients. Between T0 and T1 (weeks 1-4) Group 1 received the intervention and Group 2 received standard care. Between T1 and T2 (weeks 5-8) Group 1 received standard care and Group 2 received the intervention. The intervention was a group education session on RRT options held in the patient's home given by social workers. Patients invited members from their social network to attend. Self-report questionnaires were used at T0, T1 and T2 to measure patients' knowledge and communication, and concepts from the Theory of Planned Behaviour such as attitude. Comparable questionnaires were completed pre-post intervention by 229 attendees. Primary RRT was registered up to 2 years post-intervention. Multilevel linear modelling was used to analyse patient data and paired t-tests for attendee data. RESULTS: Statistically significant increases in the primary targets knowledge and communication were found among patients and attendees after receiving the intervention. The intervention also had a significant effect in increasing positive attitude toward living donation and haemodialysis. Of the 80 participants, 49 underwent RRT during follow-up. Of these, 34 underwent a living donor kidney transplant, of which 22 were pre-emptive. CONCLUSIONS: Early home-based group education supports informed decision-making regarding primary RRT for ESRD patients and their social networks and may remove barriers to pre-emptive transplantation.

The impact of the donors' and recipients' medical complications on living kidney donors' mental health.

A minority of living kidney donors (between 5-25%) have poor psychological outcomes after donation. There is mixed evidence on the influence of medical complications on these outcomes. We examined whether medical complications among donors and recipients predicted changes in donors' mental health (psychological symptoms and well-being) between predonation and 1 year postdonation. One-hundred and forty-five donors completed questionnaires on mental health predonation and 3 and 12 months postdonation. Number of recipient rehospitalizations and donor complications (none; minor; or severe) were obtained from medical records at 3 and 12 months after surgery. Multilevel regression analyses were used to examine the association between medical complications and changes in donors' mental health over time after controlling for sociodemographic characteristics. We found that donor complications (P = 0.003) and recipient rehospitalizations (P = 0.001) predicted an increase in donors' psychological symptoms over time. Recipient rehospitalizations also predicted a decrease in well-being (P = 0.005) over time; however, this relationship became weaker over time. We conclude that medical complications experienced by either the donor or recipient is a risk factor for deterioration in donors' mental health after living kidney donation. Professionals should monitor donors who experience medical complications and offer additional psychological support when needed.

LOng-term follow-up after liVE kidney donation (LOVE) study: a longitudinal comparison study protocol.

BACKGROUND: The benefits of live donor kidney transplantation must be balanced against the potential harm to the donor. Well-designed prospective studies are needed to study the long-term consequences of kidney donation. METHODS: The "LOng-term follow-up after liVE kidney donation" (LOVE) study is a single center longitudinal cohort study on long-term consequences after living kidney donation. We will study individuals who have donated a kidney from 1981 through 2010 in the Erasmus University Medical Center in Rotterdam, The Netherlands. In this time period, 1092 individuals donated a kidney and contact information is available for all individuals. Each participating donor will be matched (1:4) to non-donors derived from the population-based cohort studies of the Rotterdam Study and the Study of Health in Pomerania. Matching will be based on baseline age, gender, BMI, ethnicity, kidney function, blood pressure, pre-existing co-morbidity, smoking, the use of alcohol and highest education degree. Follow-up data is collected on kidney function, kidney-related comorbidity, mortality, quality of life and psychological outcomes in all participants. DISCUSSION: This study will provide evidence on the long-term consequences of live kidney donation for the donor compared to matched non-donors and evaluate the current donor eligibility criteria. TRIAL REGISTRATION: Dutch Trial Register NTR3795 .