5 research outputs found
Raising awareness of unspecified living kidney donation: An ELPAT
Background: Living donor kidney transplantation (LDKT) is the preferred treatment for patients with end-stage renal disease and unspecified living kidney donation is morally justified. Despite the excellent outcomes of LDKT, unspecified kidney donation (UKD) is limited to a minority of European countries due to legal constraints and moral objections. Consequently, there are significant variations in practice and approach between countries and the contribution of UKD is undervalued. Where UKD is accepted as routine, an increasing number of patients in the kidney exchange programme are successfully transplanted when a 'chain' of transplants is triggered by a single unspecified donor. By expanding the shared living donor pool, the benefit of LDKT is extended to patients who do not have their own living donor because a recipient on the national transplant list always completes the chain. Is there a moral imperative to increase the scope of UKD and how could this be achieved? Methods: An examination of the literature and individual country practices was performed to identify the limitations on UKD in Europe and recommend strategies to increase transplant opportunities. Results: Primary limitations to UKD, key players and their roles and responsibilities were identified. Conclusions: Raising awareness to encourage the public to volunteer to donate is appropriate and desirable to increase UKD. Recommendations are made to provide a framework for increasing awareness and engagement in UKD. The public, healthcare professionals, policy makers and society and religious leaders have a role to play in creating an environment for change
Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial
We report results of a phase 2, randomized, multicenter, open‐label, two‐arm study
evaluating the safety and efficacy of eculizumab in preventing acute antibody‐
mediated rejection (AMR) in sensitized recipients of living‐donor kidney transplants
requiring pretransplant desensitization (NCT01399593). In total, 102 patients under‐
went desensitization. Posttransplant, 51 patients received standard of care (SOC)
and 51 received eculizumab. The primary end point was week 9 posttransplant treat‐
ment failure rate, a composite of: biopsy‐proven acute AMR (Banff 2007 grade II or
III; assessed by blinded central pathology); graft loss; death; or loss to follow‐up. Eculizumab was well tolerated with no new safety concerns. No significant difference
in treatment failure rate was observed between eculizumab (9.8%) and SOC (13.7%;
P = .760). To determine whether data assessment assumptions affected study out‐
come, biopsies were reanalyzed by central pathologists using clinical information. The
resulting treatment failure rates were 11.8% and 21.6% for the eculizumab and SOC
groups, respectively (nominal P = .288). When reassessment included grade I AMR,
the treatment failure rates were 11.8% (eculizumab) and 29.4% (SOC; nominal
P = .048). This finding suggests a potential benefit for eculizumab compared with
SOC in preventing acute AMR in recipients sensitized to their living‐donor kidney
transplants (EudraCT 2010‐019630‐28)
Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies
Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan–Meier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q−) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q−) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30–1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d−); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d−) years; HR 0.38; 95% CI 0.15–0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction