Wight J, Chilcott J, Holmes M, Brewer N
The School of Health and Related Research, University of Sheffield, UK.
Health Technol Assess. 2003;7(25):1-94. doi: 10.3310/hta7250.
To evaluate the clinical and cost-effectiveness of machine perfusion (MP) compared to cold storage (CS), as a means of preserving kidneys prior to transplantation. Transplantation of kidneys from both heart-beating donors (HBDs) and non-heart-beating donors (NHBDs) is considered. Finally to review whether the use of MP can allow valid testing of kidney viability prior to transplantation.
Fifteen electronic bibliographic databases were searched. The reference lists of relevant articles and sponsor submissions were hand searched and various health service research-related resources were consulted via the Internet.
A literature search was undertaken to identify relevant studies and a meta-analysis performed on the studies that had appropriate comparator groups and reported sufficient data. A structured review examined tests of viability of kidneys on MP. Economic modelling was used to determine the cost-effectiveness and cost-utility of MP.
The meta-analysis suggested that the use of MP, as compared with CS, is associated with a relative risk of delayed graft function (DGF) of 0.804 (95% confidence limits 0.672 to 0.961). There was no evidence to suggest that this effect is different in kidneys taken from HBDs as opposed to NHBDs. Meta-analysis of 1-year graft survival data showed no significant effect, but the studies, even when aggregated, were severely underpowered with respect to the likely impact on graft survival. The size of effects demonstrated were in line with those predicted by an indirect model of graft survival based on the association of DGF with graft loss. The economic assessment indicated that it is unlikely that in the UK health setting complete cost recovery will be obtained from a reduction in the incidence of DGF. The probability that MP is cheaper and more effective than CS in the long term was estimated at around 80% for NHBD recipients and 50-60% for HBD recipients. Flow characteristics of the perfusate of kidneys undergoing MP may be an indicator of kidney viability, but data were inadequate to calculate the sensitivity and specificity of any test based on this. The concentration of alpha-glutathione-S-transferase (a marker of cell damage) in the perfusate may be the basis of a valid test. A threshold of 2800 micrograms/100 g gave a sensitivity of 93% and specificity of 33% (and hence a likelihood ratio of 1.41).
The baseline analysis indicated that in the long-term MP would be expected to be cheaper and more effective than CS for both HBD and NHBD recipients. A definitive study of the clinical benefit of MP in order to establish its effect on DGF and longer term graft survival would be valuable, together with an economic evaluation of the benefits. While direct evidence relating to improvements in graft survival would be preferable, the small predicted improvement indicates that a very large sample size would be required. In addition to seeking direct evidence of the impact on DGF, research quantifying the impact of DGF on graft survival in this technology is required. Research is also needed to establish whether a valid test (or combination of tests) of kidney viability can be developed.
评估与冷藏（CS）相比，机器灌注（MP）作为肾脏移植前肾脏保存方法的临床效果和成本效益。同时考虑来自心跳骤停供体（HBDs）和非心跳骤停供体（NHBDs）的肾脏移植情况。最后，回顾MP的使用是否能在移植前对肾脏活力进行有效检测。
检索了15个电子文献数据库。手工检索了相关文章的参考文献列表和资助机构提交的材料，并通过互联网查阅了各种与卫生服务研究相关的资源。
进行文献检索以识别相关研究，并对具有适当对照分组且报告了充分数据的研究进行荟萃分析。通过结构化综述检查了MP上肾脏活力的检测方法。采用经济模型来确定MP的成本效益和成本效用。
荟萃分析表明，与CS相比，使用MP会使移植肾功能延迟（DGF）的相对风险为0.804（95%置信区间为0.672至0.961）。没有证据表明这种效果在来自HBDs的肾脏与NHBDs的肾脏之间存在差异。对1年移植肾存活数据的荟萃分析未显示出显著效果，但这些研究即使汇总起来，在对移植肾存活的可能影响方面也存在严重的功效不足。所显示的效果大小与基于DGF与移植肾丢失关联的移植肾存活间接模型预测的结果一致。经济评估表明，在英国卫生环境下，不太可能通过降低DGF的发生率来实现完全成本回收。估计从长期来看，MP比CS更便宜且更有效的概率，对于NHBD受者约为80%，对于HBD受者为50 - 60%。接受MP的肾脏灌注液的流动特性可能是肾脏活力的一个指标，但数据不足以计算基于此的任何检测的敏感性和特异性。灌注液中α - 谷胱甘肽 - S - 转移酶（细胞损伤标志物）的浓度可能是有效检测的基础。阈值为2800微克/100克时，敏感性为93%，特异性为33%（因此似然比为1.41）。
基线分析表明，从长期来看，对于HBD和NHBD受者，MP预计比CS更便宜且更有效。对MP的临床益处进行确定性研究以确定其对DGF和长期移植肾存活的影响将是有价值的，同时进行效益的经济评估。虽然有关移植肾存活改善的直接证据会更好，但预测的微小改善表明需要非常大的样本量。除了寻求对DGF影响的直接证据外，还需要研究量化该技术中DGF对移植肾存活的影响。还需要开展研究以确定是否能够开发出有效的肾脏活力检测方法（或检测方法组合）。
