Schaapherder Alexander F, Kaisar Maria, Mumford Lisa, Robb Matthew, Johnson Rachel, de Kok Michèle J C, Bemelman Frederike J, van de Wetering Jacqueline, van Zuilen Arjan D, Christiaans Maarten H L, Baas Marije C, Nurmohamed Azam S, Berger Stefan P, Bastiaannet Esther, de Vries Aiko P J, Sharples Edward, Ploeg Rutger J, Lindeman Jan H N
Department of Surgery and Leiden Transplant Center, Leiden University Medical Center, Leiden, the Netherlands.
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
EClinicalMedicine. 2022 Jun 25;50:101516. doi: 10.1016/j.eclinm.2022.101516. eCollection 2022 Aug.
Donor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft for transplantation. While this may improve outcomes, the performance characteristics of the algorithms remains moderate. To estimate the impact of donor factors of grafts accepted for transplantation on transplant outcomes, and to test whether implementation of donor-characteristics-based algorithms in clinical decision-making is justified, we applied an instrumental variable analysis to outcomes for kidney donor pairs transplanted in different individuals.
This analysis used (dis)congruent outcomes of kidney donor pairs as an instrument and was based on national transplantation registry data for all donor kidney pairs transplanted in separate individuals in the Netherlands (1990-2018, 2,845 donor pairs), and the United Kingdom (UK, 2000-2018, 11,450 pairs). Incident early graft loss (EGL) was used as the primary discriminatory factor. It was reasoned that a scenario with a dominant impact of donor variables on transplantation outcomes would result in high concordance of EGL in both recipients, whilst dominance of asymmetrical outcomes could indicate a more complex scenario, involving an interaction of donor, procedural and recipient factors.
Incidences of congruent EGL (Netherlands: 1·2%, UK: 0·7%) were slightly lower than the arithmetical (stochastic) incidences, suggesting that once a graft has been accepted for transplantation, donor factors minimally contribute to incident EGL. A long-term impact of donor factors was explored by comparing outcomes for functional grafts from donor pairs with asymmetrical vs. symmetrical outcomes. Recipient survival was similar for both groups, but a slightly compromised graft survival was observed for grafts with asymmetrical outcomes in the UK cohort: (10-years Hazard Ratio for graft loss: 1·18 [1·03-1·35] p<0·018); and 5 years eGFR (48·6 [48·3-49·0] vs. 46·0 [44·5-47·6] ml/min in the symmetrical outcome group, p<0·001).
Our results suggest that donor factors for kidney grafts deemed acceptable for transplantation impact minimally on transplantation outcomes. A strong reliance on donor factors and/or donor-characteristics-based decision algorithms could result in unjustified rejection of grafts. Future efforts to optimize transplant outcomes should focus on a better understanding of the recipient factors underlying transplant outcomes.
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供体特征以及基于供体特征的决策算法正逐渐应用于决定是否接受可用的供体肾移植的决策过程中。虽然这可能会改善移植结果,但这些算法的性能特征仍处于中等水平。为了评估被接受用于移植的移植物的供体因素对移植结果的影响,并检验在临床决策中实施基于供体特征的算法是否合理,我们对在不同个体中进行移植的肾供体对的结果应用了工具变量分析。
本分析使用肾供体对的(不)一致结果作为工具,基于荷兰(1990 - 2018年,2845对供体对)和英国(2000 - 2018年,11450对)所有在不同个体中进行移植的供体肾对的国家移植登记数据。早期移植物丢失(EGL)作为主要的鉴别因素。据推测,如果供体变量对移植结果有主导影响,那么两个受者的EGL一致性会很高,而不对称结果占主导则可能表明情况更复杂,涉及供体、手术和受者因素的相互作用。
一致EGL的发生率(荷兰:1.2%,英国:0.7%)略低于算术(随机)发生率,这表明一旦移植物被接受用于移植,供体因素对早期EGL的影响最小。通过比较来自供体对的功能正常移植物的不对称结果与对称结果的移植结果,探讨了供体因素的长期影响。两组受者的生存率相似,但在英国队列中,不对称结果的移植物的移植生存率略有下降:(移植物丢失的10年风险比:1.18 [1.03 - 1.35],p < 0.018);对称结果组的5年估算肾小球滤过率为48.6 [48.3 - 49.0],而不对称结果组为46.0 [44.5 - 47.6] ml/min,p < 0.001)。
我们的结果表明,被认为可接受用于移植的肾移植物的供体因素对移植结果的影响最小。过度依赖供体因素和/或基于供体特征的决策算法可能导致对移植物的不合理拒绝。未来优化移植结果的努力应集中在更好地理解移植结果背后的受者因素上。
无。