Shaw Martin
Argutus Medical Inc., Dublin, Ireland.
Methods Mol Biol. 2010;641:271-302. doi: 10.1007/978-1-60761-711-2_16.
Histopathology is the gold standard for defining renal injury, but it is invasive, time-consuming and expensive, plus it is seldom used in subjects with mild renal injury. Using biomarkers linked to distinct, defined cell types and tissues provides a direct link to histopathology without its drawbacks, plus it provides increased sensitivity, and specificity. The nephron consists of several sections, each with its own specific biomarkers; therefore, by the use of a battery of tests injuries can be localised to distinct areas of it. Using urine samples simplifies repeated sampling from the same subject or animal leading to better defined toxicokinetics and disease monitoring.Serum creatinine is the most widely used renal biomarker in spite of its known shortcomings. Cell-specific biomarkers are more specific and sensitive and have been known for over 40 years, but they are still underused in renal medicine and research. In particular, while many studies have shown cell-specific biomarkers to be valuable in diagnosis, there are few studies where they have been used to guide therapy or linked to quantitative changes in the kidney. Furthermore, the great majority of cell-specific biomarkers are from the proximal tubule, which may have hindered research into the study of conditions where the distal tubules are affected. Recently, the range of biomarkers and their applications has been expanded by the introduction of indicators of cellular regeneration.This chapter will discuss how using biomarkers with a known cellular origin, renal effects may be found earlier and at lower levels of injury. Their use in both renal medicine and drug research will be presented. Knowledge of these existing markers lays the foundation for evaluation, comparison, and characterisation of new markers that will be identified in the future.
组织病理学是定义肾损伤的金标准,但它具有侵入性、耗时且昂贵,此外在轻度肾损伤患者中很少使用。使用与不同的、明确的细胞类型和组织相关的生物标志物可直接关联到组织病理学,且没有其缺点,还能提高敏感性和特异性。肾单位由几个部分组成,每个部分都有其特定的生物标志物;因此,通过一系列检测,损伤可定位到肾单位的不同区域。使用尿液样本简化了对同一受试者或动物的重复采样,从而能更好地确定毒代动力学并进行疾病监测。尽管血清肌酐存在已知缺点,但它仍是最广泛使用的肾脏生物标志物。细胞特异性生物标志物更具特异性和敏感性,并且已经存在40多年了,但它们在肾脏医学和研究中的应用仍然不足。特别是,虽然许多研究表明细胞特异性生物标志物在诊断中有价值,但很少有研究将它们用于指导治疗或与肾脏的定量变化相关联。此外,绝大多数细胞特异性生物标志物来自近端小管,这可能阻碍了对远端小管受影响情况的研究。最近,通过引入细胞再生指标,生物标志物的范围及其应用得到了扩展。本章将讨论如何使用具有已知细胞来源的生物标志物,更早且在更低损伤水平下发现肾脏效应。还将介绍它们在肾脏医学和药物研究中的应用。了解这些现有标志物为评估、比较和表征未来将发现的新标志物奠定了基础。