Feinstein A R, Heinemann L A, Curhan G C, Delzell E, Deschepper P J, Fox J M, Graf H, Luft F C, Michielsen P, Mihatsch M J, Suissa S, Van Der Woude F, Willich S
Departments of Medicine and Epidemiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Kidney Int. 2000 Dec;58(6):2259-64. doi: 10.1046/j.1523-1755.2000.00410.x.
The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years.
A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to critically review data on the relationship between nonphenacetin combined analgesics and nephropathy.
The committee regarded epidemiologic evidence on nonphenacetin combined analgesics as inconclusive because of sparse information and substantial methodological problems. The committee also noted that a diagnosis of analgesic-associated nephropathy (AAN) in clinical practice usually depends on information about exposure before or in the early stages of the disease and is seldom accompanied by specific histologic evidence. The morphologic finding of papillary calcification can arise from other conditions and is not specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic procedure. In the limited amount of experimental pharmacological data in humans and animals, the committee found no convincing evidence to confirm or refute the hypothesis that nonphenacetin combined analgesics are more nephrotoxic than single formulations. For caffeine taken with combined analgesics, the currently available information is not sufficient to postulate a harmful toxicological effect.
The committee's two main conclusions were that sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy and that new studies should be done to provide appropriate data for resolving the question.
关于不含非那西丁的复合镇痛药与肾脏疾病之间关联的争论已持续数年。
由德国、瑞士和奥地利的监管机构以及制药行业联合挑选的一个科学家同行评审委员会，被要求严格审查关于非那西丁复合镇痛药与肾病之间关系的数据。
由于信息稀少和大量方法学问题，该委员会认为关于非那西丁复合镇痛药的流行病学证据尚无定论。该委员会还指出，临床实践中镇痛剂相关性肾病（AAN）的诊断通常取决于疾病之前或早期阶段的暴露信息，并且很少伴有特定的组织学证据。乳头钙化的形态学发现可能由其他情况引起，并非AAN所特有。出于这些原因，应该用科学方法重新评估AAN的识别标准，以验证诊断程序。在有限的人体和动物实验药理学数据中，该委员会没有发现令人信服的证据来证实或反驳非那西丁复合镇痛药比单一制剂更具肾毒性这一假设。对于复合镇痛药中所含的咖啡因，目前可得的信息不足以假定其具有有害的毒理学效应。
该委员会的两个主要结论是，没有足够的证据表明非那西丁复合镇痛药与肾病有关，并且应该开展新的研究以提供解决该问题的适当数据。
