MONITORING OF EARLY NEPHROTOXIC EFFECTS OF INDUSTRIAL-CHEMICALS
MONITORING OF EARLY NEPHROTOXIC EFFECTS OF INDUSTRIAL-CHEMICALS
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DOI：
10.1016/0378-4274(92)90170-o
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发表时间：
1992-12-01
影响因子：
3.5
通讯作者：
CARDENAS, A
中科院分区：
文献类型：
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作者：
LAUWERYS, R;BERNARD, A;CARDENAS, A
长期接触某些工业化学品(例如，重金属、一些卤代烃)可能会导致肾脏进行性退行性变化，可能导致肾功能不全。最广泛用于评估肾脏完整性的筛查试验(即血清肌酐或尿素氮和定量或半定量测定总蛋白尿)缺乏敏感性；它们不允许在移除暴露可防止疾病进展的阶段检测肾脏损害，也不适合确定潜在肾毒性化学物质的无影响水平。在过去的几十年中，人们提出了新的标记物来早期检测肾实质不同部位的结构和/或功能变化。一些检查主要试图评估肾小球的完整性(例如，高MR蛋白尿，如转铁蛋白尿和蛋白尿；肾小球基底膜或系膜基质某些成分的排泄增加，低MR蛋白的血浆浓度增加，如β2-微球蛋白和游离视黄醇结合蛋白)，近端小管(例如，几种低MR血浆蛋白、小管酶和抗原的排泄)，Henle环和远端小管(例如，各种前列腺素的排泄)。目前，这些测试中的大多数在个人层面上的价值有限，因为它们的健康意义，即使在它们持续异常的情况下，也尚未得到充分的研究。然而，在接触镉的工人中，已经表明持续的低MR蛋白尿预示着与年龄相关的GFR下降的加剧；这种生物学变化应该被认为是不利的影响。目前，这些测试的主要应用是在流行病学研究的框架内，旨在评估肾毒性污染物的允许暴露水平。基于一大组肾脏标志物的剂量-效应/反应关系的研究使我们能够更好地确定镉的内部剂量，这与重大的肾脏风险无关。
Long-term exposure to certain industrial chemicals (e.g. heavy metals, some halogenated hydrocarbons) may cause progressive degenerative changes in the kidney, possibly leading to renal insufficiency. The screening tests most widely used to assess the integrity of the kidney (i.e. serum creatinine or BUN and the quantitative or semi-quantitative measurement of total proteinuria) lack sensitivity; they do not permit the detection of renal disturbances at a stage when removal from exposure may prevent progression of the disease process and are not suitable to determine the no-effect levels of potentially nephrotoxic chemicals.During the last decades new markers have been proposed for the early detection of structural and/or functional changes at various sites of the renal parenchyma. Some tests mainly attempt to assess the integrity of the glomerulus (eg. high Mr proteinuria such as transferrinuria and albuminuria; increased excretion of some components of the glomerular basement membrane or the mesangium matrix, increased plasma concentration of low Mr proteins such as beta2-microglobulin and free retinol binding protein), the promixal tubule (e.g. urinary excretion of several low Mr plasma proteins, tubular enzymes and antigens), the loop of Henle and distal tubule (e.g. excretion of various prostanoids). Currently, the majority of these tests are of limited value at the individual level because their health significance, even when they are persistently abnormal, has not yet been sufficiently studied. In workers exposed to Cd, however, it has been shown that a persistent low Mr proteinuria is predictive of an exacerbation of the age-related decline of the GFR; this biological change should be considered as an adverse effect.Currently, the principal application of these tests lies in the framework of epidemiologic studies designed to assess permissible exposure levels to nephrotoxic pollutants. The study of dose-effects/response relationships based on a large battery of renal markers has allowed the better determination of the internal dose of Cd, which is not associated with significant renal risk.