Potential living kidney donors' positive experiences of an information letter from healthcare: a descriptive qualitative study.

BACKGROUND: Patients who need a live donor kidney transplant (LDKT) must often ask potential donors (PLDs) themselves. This is a difficult task and healthcare could unburden them by making this first contact, ensuring also that PLDs receive correct information. We investigated how PLDs experience receiving a letter from healthcare about LDKT, live kidney donation, and inviting them to meet with professionals to get more information. METHODS: The letter (LD-letter) was sent to a cohort of 46 individuals, from which a purposeful sample of 15 were interviewed using a semi-structured guide covering their experience of the letter, views on being approached by healthcare, and opinions on style and content. Interviews were analyzed using conventional inductive analysis. RESULTS: We identified three categories of experiences: Category (1) Reflections on receiving the letter, contains three subcategories relating to how the letter did not induce pressure to donate, did not affect the PLD's relationship with the patient with kidney disease, and made the letter-receiver feel important in the transplant process; Category (2) The letter creates clarification and trust, also contains three subcategories, relating to how it clarified the voluntariness of donation and neutrality of healthcare providers with respect to the PLD's decision, elucidated the patient with kidney disease's current stage of disease (where transplantation was approaching), and unburdened patients from the responsibility of contacting PLDs on their own; Category (3) Opinions and suggestions about the letter and further communication, with four subcategories, relating to preference of a letter as the first step for communication about LDKT, suggestions on style and content, views on following up the letter, and how open meetings about LDKT were an important information source. Furthermore, 80% of the interviewees found the letter's information comprehensive, 67% found it easy to read and respectful, and 86% rated it as good or very good. CONCLUSION: Potential donors prefer and recommend a letter as the first step for communication regarding LD. The LD-letter unburdens patients from the task of asking PLDs and stresses the voluntariness of donation, does not leave PLDs feeling coerced or lead to negative effects in their relationship with the patient.

From hesitation to appreciation: the transformation of a single, local donation-nurse project into an established organ-donation service.

This study evaluates the transition from a local project to promote organ donation to a permanent county-based donation service inspired by the Spanish model. To address the problem of declining donation rates, a project with one donation-specialized nurse (DOSS) was initiated at a single neuro-intensive care unit. This project was later expanded into a permanent on-call service consisting of seven DOSSes, covering a large urban county. During the different periods (before, during project and during permanent service), the DOSS function's effect on donation rates was significant, and the number of eligible donors that became actual donors increased from 37% to 73% and 74%, respectively. The effect on family vetoes was as prominent with a decrease from 34% to 8% and 14%. The staff appreciation of the DOSS function was also evident during the periods; all areas included in the questionnaire (family care, donor care and staff support) have improved greatly owing to the DOSS. The transition from a single, local donation-nurse project, to an on-call service with several DOSSes covering a large urban county was a success considering the donation rates as well as the staff's appreciation. Hence, organizational models from abroad can be adjusted and successfully adopted.

Rat islets are not rejected by anti-islet antibodies in mice treated with costimulation blockade.

BACKGROUND: Costimulation blockade can prevent rejection of islet xenografts in naïve but not sensitized recipients. Donor-specific antibodies (DSA) may partly explain this observation. The effect of DSA on rat islet xenograft survival in mice receiving costimulation blockade was investigated. METHODS: Naïve C57BL/6 mice with alloxan-induced diabetes were transplanted under the left kidney capsule with 100 Lewis rat islets. Recipients were divided into three groups receiving: (i) isotype control antibodies (Abs); (ii) anti-CD154 and CTLA4Ig; or (iii) anti-CD154, CTLA4Ig, and anti-LFA-1 every second day, day 0-8. At the time of transplantation (Tx), half of the animals in each group received naïve mouse serum and half xenoimmune serum derived from mice previously transplanted with rat islets. Non-fasting blood glucose levels and body weight were followed daily. Cured mice were examined by intraperitoneal glucose tolerance (IPGT) tests at 1 and 4 months after transplantation. RESULTS: Donor-specific antibodies were detected in immune serum-injected recipients up to at least 96 h post-Tx. Short term (≤96 h), there was no significant difference with regard to graft mass, infiltrating and apoptotic cells between groups of mice receiving naïve and immune sera. A moderate infiltration of polymorphonuclear and mononuclear cells was seen 96 h post-Tx in mice given control Abs, whether or not they received immune or naïve mouse serum. Mice given costimulation blockade had well-maintained endocrine tissue and very little cell infiltration. There was no significant difference in islet xenograft function and survival long term between groups receiving naïve and immune sera in combination with costimulation blockade. About half of the mice receiving costimulation blockade lost graft function within 110 days. CONCLUSION: The presence at Tx of DSA does not appear to negatively influence early and late islet xenograft survival in mice receiving costimulation blockade.

Red Flags in the Living Kidney Donor Process.

BACKGROUND: Ideally, no live kidney donor should regret their decision or feel they were not fully prepared for the process. Unfortunately, this is not a reality for all donors. The aim of our study is to identify areas for improvement, focusing on factors (red flags) that predict less favorable outcomes from a donor perspective. MATERIALS AND METHODS: A total of 171 living kidney donors responded to a questionnaire with 24 multiple-choice questions and space for comments. Less favorable outcomes were defined as lower satisfaction, extended physical recovery period, long-term fatigue, and longer sick leave. RESULTS: Ten red flags were identified. Of these factors, more fatigue (range, P = .000-0.040) or pain (range, P = .005-0.008) than expected while still in hospital, the actual experience being harder or different than expected (range, P = .001-0.010), and the donor wishing to have had but not having been offered a previous donor as mentor (range, P = .008-.040) correlated significantly with at least 3 of the 4 less favorable outcomes. Another significant red flag was keeping existential issues to oneself (P = .006). CONCLUSION: We identified several factors indicating that a donor could be at an increased risk for a less favorable outcome after donation. Four of these factors have, to our knowledge, not been described earlier: more early fatigue than expected, more postoperative pain than anticipated, not having been offered a mentor at an early stage, and keeping existential issues to oneself. Attention to these red flags already during the donation process could help health care professionals to act early to avoid unfavorable outcomes.

Using HTK for prolonged pancreas preservation prior to human islet isolation.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) has been established as an alternative to University-of-Wisconsin solution (UWS) for abdominal organ preservation, but data about HTK efficiency to preserve pancreata during prolonged cold ischemia time (CIT) are conflicting. In human islet transplantation, HTK provided similar isolation outcomes after short CIT. The present study aimed to investigate whether islets can be successfully isolated from HTK-preserved pancreata after prolonged CIT compared with UWS. MATERIALS AND METHODS: Sixty-four human pancreata retrieved from donors meeting criteria for kidney donation were perfused utilizing either HTK or UWS and preserved for more or less than 10 h prior to islet isolation. Along with parameters related to isolation and islet quality assessment, the dry-to-wet weight ratio was evaluated. RESULTS: Donor- and procurement-related factors did not vary between HTK- and UWS-perfused pancreata. The dry-to-wet weight ratio was lower in HTK-preserved pancreata indicated tissue edema (21.0% ± 3.5% versus 24.8% ± 2.0%, P = 0.007). Isolation-related variables differed between experimental groups after prolonged CIT with respect to purified packed tissue volume (9.1 ± 5.0 versus 17.2 ± 8.1 µL/g, P = 0.004) and islet yield (1910 ± 980 versus 3150 ± 1420 IE/g, P = 0.012). Islet purity and survival after culture were similar after HTK or UWS perfusion. The preservation solution did not affect in vitro function and transplantability of isolated islets. CONCLUSIONS: Compared with UWS, HTK has similar efficiency to preserve human pancreata for subsequent islet isolation during <10 h CIT but seems to be limited for prolonged cold storage.

The kidney recipient's path to transplantation: a comparison between living and deceased kidney donor recipients in Stockholm, Sweden.

BACKGROUND: Much remains to be done to facilitate the transplantation process for patients with end-stage renal disease. The aim here was to explore these patients' experiences of the donation process and factors related to whether the actual donors of the recipients were living or deceased and describe which issues needed attention in a quality development project. METHOD: A specially constructed questionnaire was sent to 246 recipients of living and deceased kidney transplants who had been transplanted at the Karolinska University Hospital in Stockholm, Sweden. The response rate was 87%. RESULTS: Six conditions were identified as problematic: --Most living-donor kidney recipients perceived the evaluation period for the donors as too long. --Although a living donor was available, most living-donor kidney recipients had to undergo dialysis for a relatively long period. --A majority of the patients perceived it difficult to ask for a donation. Deceased-donor kidney recipients were least satisfied with the offered support in finding a living donor. --Patients perceived fear as the main reason for potential living donors to refuse donation. --About one-fourth of living-donor kidney recipients thought that the donors were abandoned by healthcare after nephrectomy. --Older patients and singles were least likely to receive a living-donor kidney. CONCLUSIONS: The problem issues outlined above should be scrutinized and improved. Checking these issues can be used in quality control when analysing living kidney donation at local and national levels.

The critical pathway for deceased donation: reportable uniformity in the approach to deceased donation.

The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification and referral of possible deceased donors.

From words to action--influence of two organ donation campaigns on knowledge and formal decision making.

INTRODUCTION: In Sweden, two donation campaigns have been carried out; one short term (STC) during October 2001, and one long term (LTC) between the years 2003-2005. The goal was not only to inform the public but also to create a positive attitude, make people talk about donation and formally declare their decision. METHODS: The effects of the two campaigns were evaluated through three opinion polls. RESULTS: The willingness to donate was widespread (86%) before and after the campaigns. The LTC increased the knowledge of the Donor Card (24-35%, p < 0.001) and the National Donor Registry (19-40%, p < 0.001). The LTC focused on making people register, still though, only a small increase of registrants was found (11-14%, p = 0.043). The proportion expecting the question of organ donation if their relative was to die under circumstances that made organ donation possible increased (73-79%, p = 0.002). No corresponding increase was found regarding the number having informed a relative about their decision (20-23%, ns). CONCLUSION: The LTC was successful in increasing the expectation for the donation request. It also improved the knowledge of the Card and the Registry and slightly increased the number having registered. However, neither of the campaigns succeeded in making people inform their relatives.

Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation: studies in a rodent model.

Islet graft survival inside macroencapsulation devices is suboptimal. We hypothesized that induction of neovascularization by preimplantation of devices would improve the physiological conditions, thereby lowering the number of islets required for cure. Several rat islets were transplanted to TheraCyte immunoprotective devices implanted subcutaneously in diabetic athymic mice. Cure rates in the groups with preimplanted devices were significantly better than in those with freshly implanted devices (375 islets: 8/8 vs. 1/6, P=0.003; 125 islets: 6/6 vs. 0/7, P=0.001). Morphometric evaluations of the 125 islet groups showed higher fractional and absolute volumes of endocrine tissue in the group with preimplanted devices (P<0.001 and P=0.035, respectively). In the following dose titration study, using preimplanted devices, as low as 50 islets cured diabetic mice (100% cure, n=6). We conclude that preimplantation significantly lowers the curative dose of macroencapsulated islets to levels resembling those of free islets transplanted under the renal capsule.

What do people agree to when stating willingness to donate? On the medical interventions enabling organ donation after death.

PURPOSE OF THE STUDY: The purpose of this study is to explore donor relatives' experiences of the medical interventions enabling organ donation, as well as to examine the donor relatives' attitudes towards donating their own organs, and whether or not their experiences have influenced their own inclination to donate. METHODS: The experiences of donor relatives were explored via in-depth interviews. The interviews covered every step from the deceased family member being struck by a severe bleeding in the brain till after the organ recovery, including the medical interventions enabling organ donation. The interviews were analysed through qualitative and quantitative content analysis. RESULTS: Brain death and organ donation proved to be hard to understand for many donor relatives. The prolonged interventions provided after death in order to enable organ donation misled some relatives to believe that their family member still was alive. In general, the understanding for what treatment aimed at saving the family member and what interventions aimed at maintaining organ viability was low. However, most donor relatives were either inspired to, or reinforced in their willingness to, donate their own organs after having experienced the loss of a family member who donated organs. CONCLUSIONS: There is a need for greater transparency regarding the whole chain of events during the donation process. Yet, having experienced the donation process closely did not discourage the donor relatives from donating their own organs-but rather inspired a willingness to donate. This indicates an acceptance of the medical procedures necessary in order to enable organ donation after death.

Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients.

Exocytosis of insulin is dependent on the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex proteins in the B-cells. We assessed insulin release as well as gene and protein expression of SNARE complex protein in isolated pancreatic islets of type 2 diabetic patients (n = 4) and nondiabetic control subjects (n = 4). In islets from the diabetic patients, insulin responses to 8.3 and 16.7 mmol/l glucose were markedly reduced compared with control islets (4.7 +/- 0.3 and 8.4 +/- 1.8 vs. 17.5 +/- 0.1 and 24.3 +/- 1.2 microU . islet(-1) . h(-1), respectively; P < 0.001). Western blot analysis revealed decreased amounts of islet SNARE complex and SNARE-modulating proteins in diabetes: syntaxin-1A (21 +/- 5% of control levels), SNAP-25 (12 +/- 4%), VAMP-2 (7 +/- 4%), nSec1 (Munc 18; 34 +/- 13%), Munc 13-1 (27 +/- 4%), and synaptophysin (64 +/- 7%). Microarray gene chip analysis, confirmed by quantitative PCR, showed that gene expression was decreased in diabetes islets: syntaxin-1A (27 +/- 2% of control levels), SNAP-25 (31 +/- 7%), VAMP-2 (18 +/- 3%), nSec1 (27 +/- 5%), synaptotagmin V (24 +/- 2%), and synaptophysin (12 +/- 2%). In conclusion, these data support the view that decreased islet RNA and protein expression of SNARE and SNARE-modulating proteins plays a role in impaired insulin secretion in type 2 diabetic patients. It remains unclear, however, to which extent this defect is primary or secondary to, e.g., glucotoxicity.

The Transplantation Society's policy on interactions with China.

The Transplantation Society has for many years taken a stand against the use of organs from executed prisoners in the People's Republic of China. Recently, increasing contact between Chinese transplant programs and the international transplant community has created a need for more specific guidelines. This article presents The Transplantation Society's policy on interactions with China and also summarizes some recent positive developments.

No beneficial effect of two-layer storage compared with UW-storage on human islet isolation and transplantation.

BACKGROUND: Shipment of pancreata between distant centers is frequently associated with prolonged cold ischemia time (CIT) that leads to poorer outcomes for islet transplantation. Clinical pilot trials have indicated that oxygenation of explanted human pancreata utilizing the two-layer method (TLM) allows the use of marginal donor pancreata for islet transplantation. The present study aimed to clarify whether TLM enhances the ischemic tolerance of human pancreata. METHODS: We analyzed retrospectively the outcome of 200 human islet isolations performed after TLM preservation or storage in University of Wisconsin solution (UWS). RESULTS: Donor characteristics and digestion parameters did not vary significantly between TLM-preserved and UWS-stored pancreata. No differences were observed between experimental groups with regard to islet yield, purity, or dynamic glucose stimulation index after either short or prolonged CIT. However, CIT and stimulation index were negatively correlated in each experimental group. The isolation outcome in donors aged > or =60 years was not increased after TLM preservation when compared to UWS storage. No effect was observed regarding islet posttransplant function in recipients with established kidney grafts. CONCLUSIONS: The present study suggests that the ischemic tolerance of human pancreata cannot be extended by TLM preservation. In addition, TLM does not seem to improve the isolation outcome for pancreata from elderly donors.

Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation.

There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.

Macroencapsulation protects against sensitization after allogeneic islet transplantation in rats.

BACKGROUND: The aim of this study was to evaluate the risks of sensitization by islet grafts encapsulated in a bilaminar immunoprotective membrane. METHODS: We studied five groups of Lewis rats: one control group (no islets), two groups that received free islets (200 or 1000 s.c.), and two groups that received encapsulated ones (200 or 1000 s.c.) from Dark Agouti (DA) rats. Four weeks later, abdominal heterotopic DA-heart transplantation was performed on the same recipients. The time-to-heart graft rejection was assessed by the cessation of heart contractions. Rejection was confirmed by histological examinations. Antidonor antibodies were determined by fluorescence activated cell sorter (FACS) analysis. RESULTS: The control animals had a mean heart graft survival of 6.4 days. The free islet groups had significantly shorter heart graft survivals-i.e., 4.8 days (200 islets) and 1.0 day (1000 islets) (P < 0.001)-while those of the encapsulated islet groups were about the same as that of the control group-i.e., 6.4 days (200 islets) and 6.0 days (1000 islets). In the free islet groups, anti-DA antibodies developed in 7/10 (200 islets) and 8/8 (1000 islets) animals after the islet transplantation. In the encapsulated groups, 1/10 (200 islets) and 3/8 (1000 islets) animals developed anti-DA antibodies after these transplantations. All animals had anti-DA antibodies at the time of heart graft rejection. On histological examination all grafts showed various features of rejection. CONCLUSIONS: The bilaminar membrane protects against sensitization and prevents accelerated rejection of a subsequent vascularized graft, at least during the first month after the islet transplantation.

Prevention of Transnational Transplant-Related Crimes-What More Can be Done?

BACKGROUND: Many nations are able to prosecute transplant-related crimes committed in their territory, but transplant recipients, organ sellers and brokers, and transplant professionals may escape prosecution by engaging in these practices in foreign locations where they judge the risk of criminal investigation and prosecution to be remote. METHODS: The Declaration of Istanbul Custodian Group convened an international working group to evaluate the possible role of extraterritorial jurisdiction in strengthening the enforcement of existing laws governing transplant-related crimes across national boundaries. Potential practical and ethical concerns about the use of extraterritorial jurisdiction were examined, and possible responses were explored. RESULTS: Extraterritorial jurisdiction is a legitimate tool to combat transplant-related crimes. Further, development of a global registry of transnational transplant activities in conjunction with a standardized international referral system for legitimate travel for transplantation is proposed as a mechanism to support enforcement of national and international legal tools. CONCLUSIONS: States are encouraged to include provisions on extraterritorial jurisdiction in their laws on transplant-related crimes and to collaborate with professionals and international authorities in the development of a global registry of transnational transplant activities. These actions would assist in the identification and evaluation of illicit activities and provide information that would help in developing strategies to deter and prevent them.