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[肾胰腺移植后自由基清除剂的治疗现状]

[Status of treatment with free radical scavengers following kidney and pancreas transplantation].

作者信息

Abendroth D, Schneeberger H, Schleibner S, Illner W D, Land W

机构信息

Abteilung für Transplantationschirurgie, Chirurgische Klinik und Poliklinik, Klinikum Grosshadern, Universität München.

出版信息

Zentralbl Chir. 1992;117(9):502-8.

PMID:1441789
Abstract

AIM OF THE STUDY

The frequency of acute renal failure (ARF) after preservation and kidney transplantation is rather high. The etiology of an ARF is an interaction of multiple mechanisms as donor conditions, explantation procedure, duration of ischemia and reperfusion injury. Different experiments demonstrated, that the damage produced by reperfusion can be prevented by the scavenger of free radicals, the enzyme superoxide dismutase (SOD).

PATIENTS AND METHODS

After a double blind study, using consecutive intraarterial bovine SOD (n = 100) in kidney transplantation, showing a trend in favour to the SOD treated group, especially when long-time stored kidneys (> 30 h) had been grafted, a second study was designed to evaluate the efficiency of intravenous recombinant human SOD in the protection from ARF. This study (n = 180) was split into two different trials, double blind and randomized in itself: (A) grafts with cold ischemia time lower or equal 30 hrs., (B) cold ischemia more than 30 hrs. All grafts were preserved with Euro-collins. The study substances were either placebo or 200 mg rh-SOD (Grünenthal GmbH, FRG), given 10-2 minutes prior reperfusion intravenously. Parameters causing an ARF were equal and well comparable in both groups.

RESULTS

Concerning early graft function there was no difference in study A between placebo and rh-SOD group. In study B the average and median of the day creatinine dropped the first time without interference of hemodialysis, showed a trend in favour to the rh-SOD group. If placebo was given only 19% of the grafts gained function within the first week, when rh-SOD was applied 47% functioned in the first week. The lack of significant benefit from SOD treatment could be explained by the dependency of the proportion of the total injury caused by reperfusion compared with the proportion resulting from ischemic injury per se. The rh-SOD group showed a better 3 years graft survival rate (+16%).

CONCLUSIONS

It seems rh-SOD is able to augment the early graft function and is helpful to reduce the ARF frequency when long-time stored cadaveric kidneys have to be transplanted. These promising results encourage us to continue the study in protocol B to get greater numbers and definitive results.

摘要

研究目的

肾脏保存及移植后急性肾衰竭(ARF)的发生率颇高。ARF的病因是多种机制相互作用的结果,如供体状况、摘取过程、缺血时间及再灌注损伤。不同实验表明,自由基清除剂超氧化物歧化酶(SOD)可预防再灌注造成的损伤。

患者与方法

在一项双盲研究中,对100例肾移植患者连续动脉内注射牛SOD,结果显示SOD治疗组有一定优势,尤其是在移植长期保存(>30小时)的肾脏时。为此设计了第二项研究,以评估静脉注射重组人SOD预防ARF的效果。该研究(n = 180)本身分为两项不同的双盲随机试验:(A)冷缺血时间≤30小时的移植物;(B)冷缺血时间>30小时的移植物。所有移植物均用Euro - collins液保存。研究药物为安慰剂或200mg重组人SOD(德国格伦泰科公司),在再灌注前10 - 2分钟静脉注射。两组中导致ARF的参数相同且具有良好可比性。

结果

关于早期移植物功能,研究A中安慰剂组与重组人SOD组之间无差异。在研究B中,首次肌酐下降且无需血液透析干预的平均天数和中位数显示出对重组人SOD组有利的趋势。若给予安慰剂,仅19%的移植物在第一周内恢复功能,而应用重组人SOD时,47%的移植物在第一周内恢复功能。SOD治疗缺乏显著益处可能是由于与缺血损伤本身相比,再灌注造成的总损伤比例不同。重组人SOD组的3年移植物存活率更高(提高了16%)。

结论

重组人SOD似乎能够增强早期移植物功能,且在必须移植长期保存的尸体肾脏时,有助于降低ARF的发生率。这些有前景的结果促使我们继续对方案B进行研究,以获得更多数据和确切结果。

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