Imperfect Gold Standards for Kidney Injury Biomarker Evaluation
Imperfect Gold Standards for Kidney Injury Biomarker Evaluation
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DOI：
10.1681/asn.2010111124
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发表时间：
2012-01-01
影响因子：
13.6
通讯作者：
Bonventre, Joseph V.
中科院分区：
文献类型：
--
作者：
Waikar, Sushrut S.;Betensky, Rebecca A.;Bonventre, Joseph V.
临床医生已经使用血清肌酐在诊断测试急性肾损伤几十年，尽管其不完善的灵敏度和特异性。新的肾小管损伤生物标志物可能会彻底改变急性肾损伤的诊断;然而，即使新的肾小管损伤生物标志物是100%敏感和100%特异性的，当使用血清肌酐作为金标准时，它可能会出现不准确。急性肾损伤，如血清肌酐所定义的，可能不反映肾小管损伤，血清肌酐无变化并不能保证肾小管损伤的存在。一般来说，生物标志物的表观诊断性能不仅取决于其检测损伤的能力，还取决于疾病的患病率以及不完美金标准的灵敏度和特异性。假设在某一临界值下，血清肌酐的敏感性为80%，特异性为90%，疾病患病率为10%，那么与作为金标准的血清肌酐相比，具有真正100%灵敏度的新的完美生物标志物似乎只有47%的灵敏度。通过使用更严格的标准来诊断急性肾损伤，从而最大限度地减少错误分类，这将减少在评价研究中的生物标志物性能时的错误。使用新生物标志物的明显诊断错误可能反映了不完美的金标准本身的错误，而不是生物标志物的不良性能。本研究的结果表明，在生物标志物或干预性研究中，血清肌酐的微小变化不应单独用于定义急性肾损伤。
Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies.