Transplantation of kidneys from DCD and DBD donors who died after ligature asphyxiation: The UK experience.

There is uncertainty about whether hypoxic injury accompanying donor death from ligature asphyxiation influences renal transplant outcomes, particularly for recipients of kidneys donated after circulatory death (DCD). The UK Registry analysis was undertaken to determine transplant outcomes in recipients of kidneys from donors who died following ligature asphyxiation. From 2003 to 2016, 2.7% (n = 521) of potential organ donors died following ligature asphyxiation (mostly suicide by hanging). Of these, 409 (78.5%) donated kidneys for transplantation (46.9% donation after brain death [DBD] and 53.1% DCD donors) resulting in 650 kidney transplants. Compared to other deceased donors, those dying from ligature asphyxiation were younger, more often male, and had less hypertension. Unadjusted patient and graft survival were superior for recipients of both DBD and DCD kidneys from donors dying after ligature asphyxiation, although after adjustment for donor/recipient variables, transplant outcomes were similar. A case-control matched analysis confirmed transplant outcomes for those who received kidneys from donors dying after ligature asphyxiation were similar to controls. Although caution is required in interpreting these findings because of potential selection bias, kidneys from donors dying of ligature asphyxiation suffer an additional warm ischemic insult that does not apparently adversely influence transplant outcomes, even for kidneys from DCD donors.

Nondepleting anti-CD4 and soluble interleukin-1 receptor prevent autoimmune destruction of syngeneic islet grafts in diabetic NOD mice.

BACKGROUND: Successful islet transplantation in type 1 diabetes requires tolerance induction of both allo- and autoreactive T-cell responses. Monoclonal antibodies targeting the CD4 coreceptor on T-helper cells have been shown to be effective in this regard. In type 1 diabetes, there is some evidence to suggest that cytokines such as interleukin (IL)-1 may be involved in beta-cell destruction. The high glucose levels associated with type 1 diabetes are also known to be toxic to beta cells. METHOD: The tempo of T-cell and macrophage infiltration into syngeneic islets transplanted into diabetic nonobese diabetic (NOD) mice was examined by immunohistochemistry. We investigated the ability of a nondepleting anti-CD4 monoclonal antibody (YTS177) to induce tolerance to syngeneic islet grafts in female spontaneous diabetic NOD mice and in an adoptive transfer model of diabetes in NOD mice. The spontaneous model was used to test the effect on graft function of perioperative insulin therapy in mice treated with YTS177. The ability of soluble interleukin (sIL)-1 receptor (R) type II (sIL-1RII) to inhibit IL-1 effects in syngeneic islet transplants was also assessed. RESULTS: Cellular infiltration of CD3 cells and macrophages into the islet graft coincided with loss of graft function in untreated mice. Self-tolerance to beta cells was restored with YTS177, allowing long-term graft survival in a proportion of animals. The use of perioperative insulin therapy increased the number of successful grafts in spontaneously diabetic NOD mice treated with YTS177. The combination of YTS177 with sIL-1RII significantly improved the rates of graft survival compared with graft survival in YTS177-treated spontaneously diabetic NOD mice. CONCLUSIONS: Nondepleting anti-CD4 antibodies restore self tolerance to syngeneic islet transplants in diabetic NOD mice. Insulin therapy improves graft survival in mice treated with YTS177. Preventing the action of IL-1 greatly improves graft survival induced with YTS177.

Higher quality of life in living donor kidney transplantation: prospective cohort study.

This prospective, longitudinal cohort study investigated the effect of donating or receiving a kidney on quality of life and relationship dynamics. Forty donors and 35 recipients from two UK transplantation centres completed the World Health Organisation quality of life questionnaire (WHOQOL) with additional questionnaires before, 6 weeks and one year after operation. Before donation the donor mean quality of life score in the physical domain was 18.8. This was significantly higher than the UK value for a healthy person of 16.4 (P < 0.001). Six weeks after operation, donor score reduced to UK normative levels however improved again at one year (17.7). Recipient mean physical domain score before was 11.4, significantly lower than the UK norm (P < 0.01), increasing to 16.0 one year after. Both donor (P < 0.009) and recipient (P < 0.05) experienced a significant improvement in their mutual relationship. Recipients expressed anxiety about the donor before operation. Donors were not concerned about living with one kidney. We concluded that living kidney donation has no detrimental effect on the physical or psychological well being of donors one year after donation. Transplantation results in a major improvement in quality of life for the recipient. Most donors would donate again, if this were possible.

A report on the activity and clinical outcomes of renal non-heart beating donor transplantation in the United Kingdom.

The use of kidneys from non-heart beating donors (NHBDs) presents a paradox; whilst they provide more organs for transplantation, there is an increased risk of poor graft outcome, particularly in the short term. This study has highlighted the difference in early graft function and late graft survival between NHBD kidneys with short (controlled) and long (uncontrolled) warm ischaemic times. Whilst it would seem that it is preferable to use controlled donors only, their numbers are small. By employing a rational approach to the use of each of these types of kidney, such as structured viability assessment and risk analysis, it may be that the results of uncontrolled NHBD can be improved.