Eras J, Perazella M A
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8029, USA.
Am J Med Sci. 2001 Mar;321(3):181-90. doi: 10.1097/00000441-200103000-00005.
Selective cyclooxygenase-2 (COX-2) inhibitors have provided relief for patients suffering from chronic pain and other inflammatory conditions and have reduced adverse gastrointestinal effects. The documented reduction in gastric erosions, ulcerations, and perforations during the use of COX-2-selective inhibitors raises the question: would the kidney be similarly spared? Our understanding of these enzyme isoforms in the kidney is incomplete. However, kidney tissue seems to possess "constitutive" or homeostatic COX-2 enzyme, suggesting a role for prostaglandins produced by this isoform. In addition, studies evaluating the renal effects of the selective nonsteroidal anti-inflammatory drugs (NSAIDs) are inconclusive, and available data on the renal effects of COX-2-selective inhibitors are conflicting. Inadequate numbers, varied baseline patient characteristics, and different doses and lengths of drug treatment hampers comparison of the small number of clinical investigations available for review. Therefore, this article reviews the role of cyclooxygenase enzyme activity and associated prostaglandins in the kidney and the adverse renal effects of nonselective NSAIDs. We also touch on the COX-1/COX-2 selectivity of NSAIDs, the localization of COX enzymes in kidneys, and clinical studies examining the renal effects of selective COX-2 inhibitors.
选择性环氧化酶-2（COX-2）抑制剂为患有慢性疼痛和其他炎症性疾病的患者带来了缓解，并减少了胃肠道不良反应。使用COX-2选择性抑制剂期间，胃糜烂、溃疡和穿孔的发生率有所降低，这引发了一个问题：肾脏是否也能同样免受影响？我们对肾脏中这些酶同工型的了解并不完整。然而，肾脏组织似乎拥有“组成性”或稳态COX-2酶，这表明该同工型产生的前列腺素具有一定作用。此外，评估选择性非甾体抗炎药（NSAIDs）肾脏效应的研究尚无定论，关于COX-2选择性抑制剂肾脏效应的现有数据也相互矛盾。研究数量不足、患者基线特征各异以及药物治疗剂量和时长不同，妨碍了对少数可供审查的临床研究进行比较。因此，本文综述了环氧化酶活性及相关前列腺素在肾脏中的作用以及非选择性NSAIDs的肾脏不良反应。我们还探讨了NSAIDs的COX-1/COX-2选择性、COX酶在肾脏中的定位以及研究选择性COX-2抑制剂肾脏效应的临床研究。
