Russell J D, Churchill D N
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Am J Med. 1989 Sep;87(3):306-15. doi: 10.1016/s0002-9343(89)80156-1.
To critically review the question of whether calcium antagonists can prevent or attenuate post-ischemic acute renal failure (ARF).
Using a computer-assisted search, we identified all experimental and clinical studies published in English between 1980 and 1988 in which the main research question addressed the efficacy of verapamil, diltiazem, or nifedipine in the treatment of post-ischemic ARF. Studies were then selected for review based on clearly specified inclusion criteria and evaluated against accepted methodologic guidelines.
In experimental studies of warm renal ischemia, calcium antagonists provided significant protection of glomerular filtration rate (GFR) when given before and after ischemic injury; however, isolated pre- or post-ischemic treatment produced equivocal results. In autotransplantation studies on protracted cold ischemia, verapamil produced a modest, although physiologically significant, increase in GFR during warm reperfusion but failed to alter graft survival. Studies of calcium antagonists in humans with ARF have been confined to patients undergoing renal transplantation. Diltiazem given both to donor grafts and to recipients produced a significant reduction in the rate of delayed graft function but failed to improve one-year graft survival. This result may be due to the study of small numbers of low-risk patients. At present, there is no conclusive evidence that one calcium antagonist is more efficacious than another in the treatment of post-ischemic ARF.
Calcium antagonists appear to prevent or reduce the severity of post-ischemic ARF only when given prior to and after the ischemic insult. As a result, these agents will have most utility in the setting of renal transplantation. Although the efficacy of these agents in reducing delayed graft function appears to be established, their failure to improve graft survival is poorly understood and requires further investigation.
批判性地审视钙拮抗剂是否能够预防或减轻缺血后急性肾衰竭(ARF)这一问题。
通过计算机辅助检索,我们识别出1980年至1988年间以英文发表的所有实验性和临床研究,这些研究的主要研究问题是维拉帕米、地尔硫䓬或硝苯地平在治疗缺血后ARF中的疗效。然后根据明确规定的纳入标准选择研究进行综述,并依据公认的方法学指南进行评估。
在温性肾缺血的实验研究中,钙拮抗剂在缺血损伤前后给予时能显著保护肾小球滤过率(GFR);然而,单独的缺血前或缺血后治疗产生的结果并不明确。在长时间冷缺血的自体移植研究中,维拉帕米在温性再灌注期间使GFR有适度增加,尽管在生理上有显著意义,但未能改变移植物存活率。在ARF患者中对钙拮抗剂的研究仅限于接受肾移植的患者。给予供体移植物和受体地尔硫䓬可显著降低移植肾功能延迟恢复的发生率,但未能提高一年移植物存活率。这一结果可能归因于对少数低风险患者的研究。目前,尚无确凿证据表明在治疗缺血后ARF方面一种钙拮抗剂比另一种更有效。
钙拮抗剂似乎仅在缺血损伤前后给予时才能预防或降低缺血后ARF的严重程度。因此,这些药物在肾移植环境中将最有用。尽管这些药物在降低移植肾功能延迟恢复方面的疗效似乎已得到证实,但其未能提高移植物存活率的原因尚不清楚,需要进一步研究。