PIRCHE-II is related to graft failure after kidney transplantation

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10-1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival

Improving policy coherence for food security and nutrition in South Africa: a qualitative policy analysis

Like most other low and middle-income countries, South Africa must address a rising burden of diet-related chronic disease in a situation of persistent food insecurity and undernutrition. Supply-side policy interventions are a critical component of action to address the double burden of malnutrition. However, the food supply is governed by a number of different policy sectors, and policy incoherence can occur between government action to promote a healthy food supply and objectives for economic liberalization. We analysed the coherence of food supply policy content with respect to nutrition and food security in South Africa, and conducted 14 in-depth interviews with 22 public and private sector actors to identify opportunities to improve policy coherence across sectors governing the food supply. Drawing on Sabatier’s conceptualization of actors as influential in shaping policy outcomes, we identified three coalitions of actors related to food security and nutrition in South Africa: the dominant Economic Growth coalition, the Food Security coalition, and the Health coalition. Understanding the frames, beliefs and resources held by these coalitions offers insights into the policy tensions faced by the Government of South Africa with respect to the food supply. The analysis indicates that the current reconsideration of economic policy agendas favouring liberalization in SouthAfrica, including the termination of most bilateral investment treaties, may present an opportunity for increased recognition of food security and nutrition priorities in food supply policy making. Opportunities to strengthen policy coherence across the food supply for food security and nutrition include: specific changes to economic policy relating to the food supply that achieve both food security/nutrition and economic objectives; creating links between producers and consumers, through markets and fiscal incentives that make healthy / fresh foods more accessible and affordable; increasing formal avenues for engagement by Civil Society in nutrition and food security policy making; and including consideration of the nutritional quality of the food supply in policy objectives across sectors, to create a framework for policy coherence across sectors relating to the food supply

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient\'s HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals

Chronic and structural poverty in South Africa: Challenges for action and research

Ten years after liberation, the persistence of poverty is one of the most important and urgent problems facing South Africa. This paper reflects on some of the findings based on research undertaken as part of the participation of the Programme for Land and Agrarian Studies (PLAAS) at the University of the Western Cape in the work of the Chronic Poverty Research Centre (CPRC), situates it within the broader literature on poverty in South Africa, and considers some emergent challenges. Although PLAAS’s survey, being only the first wave of a panel study, does not yet cast light on short term poverty dynamics, it illuminates key aspects of the structural conditions that underpin long-term poverty: the close interactions between asset poverty, employment-vulnerability and subjection to unequal social power relations. Coming to grips with these dynamics requires going beyond the limitations of conventional ‘sustainable livelihoods’ analyses; and functionalist analyses of South African labour markets. The paper argues for a re-engagement with the traditions of critical sociology, anthropology and the theoretical conventions that allow a closer exploration of the political economy of chronic poverty at micro and macro level

Effect of a Single Intraoperative High-Dose ATG-Fresenius on Delayed Graft Function in Donation After Cardiac-Death Donor Renal Allograft Recipients:A Randomized Study

<p>Objectives: Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess.</p><p>Patients and Methods: We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids.</p><p>Results: The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P=.06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P <.05).</p><p>Conclusions: Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.)</p>

Psychosocial consequences of living kidney donation: a prospective multicentre study on health-related quality of life, donor-recipient relationships and regret

BACKGROUND: Previous studies have indicated decreased health-related quality of life (HRQoL) shortly after kidney donation, returning to baseline in the longer term. However, a subgroup of donors experiences persistent HRQoL problems. To identify which HRQoL aspects are impacted most by the donation and to identify at-risk donors, more specific insight into psychosocial donation consequences is needed. METHODS: The current study examined the HRQoL course, donor-perceived consequences of donation for donors, recipients and donor-recipient relationships, and regret up to 12 months post-donation in donors from seven Dutch transplantation centres. Kidney donor candidates (n = 588) completed self-report questionnaires early in the screening procedure, of which 361 (61%) donated their kidney. RESULTS: Data for 230 donors (64%) with complete assessments before donation and 6 and 12 months post-donation were analysed. Results indicated that donor physical HRQoL was comparable at all time points, except for an increase in fatigue that lasted up to 12 months post-donation. Mental HRQoL decreased at 6 months post-donation, but returned to baseline at 12 months. Donors reported large improvements in recipient's functioning and a smaller influence of the recipient's kidney disease or transplantation on the donor's life over time. A subgroup experienced negative donation consequences with 14% experiencing regret 12 months post-donation. Predictors of regret were more negative health perceptions and worse social functioning 6 months post-donation. The strongest baseline predictors of higher fatigue levels after donation were more pre-donation fatigue, worse general physical functioning and a younger age. CONCLUSIONS: Future research should examine predictors of HRQoL after donation to improve screening and to provide potential interventions in at-risk donors