Considerable Variability Among Transplant Nephrologists in Judging Deceased Donor Kidney Offers

Introduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding organ acceptance and whether the use of a prediction model impacted their decisions.Methods: We developed an observational online survey with 6 real-life cases of deceased donor kidneys offered to a waitlisted recipient. Per case, nephrologists were asked to estimate the risk of adverse outcome and whether they would accept the offer for this patient, or for a patient of their own choice, and how certain they felt. These questions were repeated after revealing the risk of adverse outcome, calculated by a validated prediction model. Results: Sixty Dutch nephrologists completed the survey. The intraclass correlation coefficient of their estimated risk of adverse outcome was poor (0.20, 95% confidence interval [CI] 0.08–0.62). Interobserver agreement of the decision on whether or not to accept the kidney offer was also poor (Fleiss kappa 0.13, 95% CI 0.129–0.130). The acceptance rate before and after providing the outcome of the prediction model was significantly influenced in 2 of 6 cases. Acceptance rates varied considerably among transplant centers. Conclusion: In this study, the estimated risk of adverse outcome and subsequent decision to accept a suboptimal donor kidney varied greatly among transplant nephrologists. The use of a prediction model could influence this decision and may enhance nephrologists’ certainty about their decision.</p

Considerable Variability Among Transplant Nephrologists in Judging Deceased Donor Kidney Offers

Introduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding organ acceptance and whether the use of a prediction model impacted their decisions. Methods: We developed an observational online survey with 6 real-life cases of deceased donor kidneys offered to a waitlisted recipient. Per case, nephrologists were asked to estimate the risk of adverse outcome and whether they would accept the offer for this patient, or for a patient of their own choice, and how certain they felt. These questions were repeated after revealing the risk of adverse outcome, calculated by a validated prediction model. Results: Sixty Dutch nephrologists completed the survey. The intraclass correlation coefficient of their estimated risk of adverse outcome was poor (0.20, 95% confidence interval [CI] 0.08–0.62). Interobserver agreement of the decision on whether or not to accept the kidney offer was also poor (Fleiss kappa 0.13, 95% CI 0.129–0.130). The acceptance rate before and after providing the outcome of the prediction model was significantly influenced in 2 of 6 cases. Acceptance rates varied considerably among transplant centers. Conclusion: In this study, the estimated risk of adverse outcome and subsequent decision to accept a suboptimal donor kidney varied greatly among transplant nephrologists. The use of a prediction model could influence this decision and may enhance nephrologists’ certainty about their decision

Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation

In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope-specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan–Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre-transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p &lt; 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA-DR, and 1 of HLA-DQ, and most antibodies were directed to HLA-B (47%). Fifty-three patients (69.7%) had DESA against one donor epitope (range 1–5). Long-term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84–3.25) in deceased donation, and 2.22 (1.25–3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA-based risk analysis on antigen level.</p

Eigenvalue asymptotics for weighted Laplace equations on rough Riemannian manifolds with boundary

Our topological setting is a smooth compact manifold of dimension two or higher with smooth boundary. Although this underlying topological structure is smooth, the Riemannian metric tensor is only assumed to be bounded and measurable. This is known as a rough Riemannian manifold. For a large class of boundary conditions we demonstrate a Weyl law for the asymptotics of the eigenvalues of the Laplacian associated to a rough metric. Moreover, we obtain eigenvalue asymptotics for weighted Laplace equations associated to a rough metric. Of particular novelty is that the weight function is not assumed to be of fixed sign, and thus the eigenvalues may be both positive and negative. Key ingredients in the proofs were demonstrated by Birman and Solomjak nearly fifty years ago in their seminal work on eigenvalue asymptotics. In addition to determining the eigenvalue asymptotics in the rough Riemannian manifold setting for weighted Laplace equations, we also wish to promote their achievements which may have further applications to modern problems

Ellipro scores of donor epitope specific HLA antibodies are not associated with kidney graft survival

In kidney transplantation, donor HLA antibodies are a risk factor for graft loss. Accessibility of donor eplets for HLA antibodies is predicted by the ElliPro score. The clinical usefulness of those scores in relation to transplant outcome is unknown. In a large Dutch kidney transplant cohort, Ellipro scores of pretransplant donor antibodies that can be assigned to known eplets (donor epitope specific HLA antibodies [DESAs]) were compared between early graft failure and long surviving deceased donor transplants. We did not observe a significant Ellipro score difference between the two cohorts, nor significant differences in graft survival between transplants with DESAs having high versus low total Ellipro scores. We conclude that Ellipro scores cannot be used to identify DESAs associated with early versus late kidney graft loss in deceased donor transplants.</p

Ellipro scores of donor epitope specific HLA antibodies are not associated with kidney graft survival

In kidney transplantation, donor HLA antibodies are a risk factor for graft loss. Accessibility of donor eplets for HLA antibodies is predicted by the ElliPro score. The clinical usefulness of those scores in relation to transplant outcome is unknown. In a large Dutch kidney transplant cohort, Ellipro scores of pretransplant donor antibodies that can be assigned to known eplets (donor epitope specific HLA antibodies [DESAs]) were compared between early graft failure and long surviving deceased donor transplants. We did not observe a significant Ellipro score difference between the two cohorts, nor significant differences in graft survival between transplants with DESAs having high versus low total Ellipro scores. We conclude that Ellipro scores cannot be used to identify DESAs associated with early versus late kidney graft loss in deceased donor transplants

Increased risk of graft failure and mortality in Dutch recipients receiving an expanded criteria donor kidney transplant

Survival of expanded criteria donor (ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non-ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18 years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences (RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8) years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [HR 1.62 (1.44–1.82)]. The adjusted HR was lower in recipients ≥60 years of age [1.32 (1.07–1.63)] than in recipients 40–59 years [1.71 (1.44–2.02) P = 0.12 for comparison with ≥60 years] and recipients 18–39 years [1.92 (1.42–2.62) P = 0.03 for comparison with ≥60 years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non-ECD grafts, especially in younger recipients (<60 years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals