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高骨铅含量的铅冶炼工人的肾功能和超滤能力

Renal function and hyperfiltration capacity in lead smelter workers with high bone lead.

作者信息

Roels H, Lauwerys R, Konings J, Buchet J P, Bernard A, Green S, Bradley D, Morgan W, Chettle D

机构信息

Unit of Industrial Toxicology and Occupational Medicine, Medical School, Catholic University of Louvain, Brussels, Belgium.

出版信息

Occup Environ Med. 1994 Aug;51(8):505-12. doi: 10.1136/oem.51.8.505.

Abstract

OBJECTIVE

The study was undertaken to assess whether the changes in urinary excretion of eicosanoids (a decrease of 6-keto-PGF1 alpha and PGF2 and an increase of thromboxane) previously found in lead (Pb) exposed workers may decrease the renal haemodynamic response to an acute oral protein load.

METHODS

The renal haemodynamic response was estimated by determining the capacity of the kidney to increase the glomerular filtration rate (in terms of creatinine clearance) after an acute consumption of cooked red meat (400 g). A cross sectional study was carried out in 76 male Pb workers (age range 30 to 60 years) and 68 controls matched for age, sex, socioeconomic state, general environment (residence), and workshift characteristics.

RESULTS

The Pb workers had been exposed to lead on average for 18 (range 6-36) years and showed a threefold higher body burden of Pb than the controls as estimated by in vivo measurements of tibial Pb concentration (Pb-T) (geometric mean 66 v 21 micrograms Pb/g bone mineral). The geometric mean concentrations of Pb in blood (Pb-B) and Pb in urine (Pb-U) were also significantly higher in the Pb group (Pb-B: 430 v 141 micrograms Pb/l; Pb-U: 40 v 7.5 micrograms Pb/g creatinine). These conditions of chronic exposure to Pb did not entail any significant changes in the concentration of blood borne and urinary markers of nephrotoxicity, such as urinary low and high molecular weight plasma derived proteins (beta 2-microglobulin, retinol binding protein, albumin, transferrin), urinary activities of N-acetyl-beta-D-glucosaminidase and kallikrein, and serum concentrations of creatinine, beta 2-microglobulin, urea, and uric acid. All participants also had normal baseline creatinine clearances (> 80 ml/min/1.73 m2) amounting on average to 115.5 in the controls v 121.3 ml/min/1.73 m2 in the Pb group. Both control and Pb exposed workers showed a significant increment in creatinine clearance (on average 15%) after oral protein load suggesting that the previously found changes in secretion of urinary eicosanoids apparently has no deleterious effect on renal haemodynamics in the examined Pb workers.

CONCLUSIONS

The finding that both baseline and stimulated creatinine clearance rates were not only significantly higher in the Pb workers but also positively correlated with Pb-T, suggests that moderate exposure to Pb may be associated with a slight hyperfiltration state, which has been found to attenuate the age related decline in baseline creatinine clearance by a factor of two. Although the relevance of this effect for the worker's health is unknown, it can be concluded that adverse renal changes are unlikely to occur in most adult male Pb workers when their blood Pb concentration is regularly kept below 700 micrograms Pb/l. One should, however, be cautious in extra-polating this conclusion to the general population because of pre-employment screening of the Pb workers for the absence of renal risk factors.

摘要

目的

本研究旨在评估先前在铅(Pb)暴露工人中发现的类二十烷酸尿排泄变化(6-酮-前列腺素F1α和前列腺素F2降低,血栓素增加)是否会降低肾脏对急性口服蛋白质负荷的血流动力学反应。

方法

通过测定急性食用熟红肉(400克)后肾脏增加肾小球滤过率(以肌酐清除率表示)的能力来评估肾脏血流动力学反应。对76名男性铅作业工人(年龄范围30至60岁)和68名年龄、性别、社会经济状况、一般环境(居住地)和工作班次特征相匹配的对照者进行了横断面研究。

结果

铅作业工人平均接触铅18年(范围6 - 36年),通过胫骨铅浓度(Pb-T)的体内测量估计,其体内铅负荷比对照组高两倍(几何平均值66对21微克铅/克骨矿物质)。铅组血液中铅(Pb-B)和尿液中铅(Pb-U)的几何平均浓度也显著更高(Pb-B:430对141微克铅/升;Pb-U:40对7.5微克铅/克肌酐)。这些慢性铅暴露情况并未导致肾毒性的血源性和尿标志物浓度发生任何显著变化,如尿中低分子量和高分子量血浆衍生蛋白(β2-微球蛋白、视黄醇结合蛋白、白蛋白、转铁蛋白)、N-乙酰-β-D-氨基葡萄糖苷酶和激肽释放酶的尿活性,以及肌酐、β2-微球蛋白、尿素和尿酸的血清浓度。所有参与者的基线肌酐清除率均正常(>80毫升/分钟/1.73平方米),对照组平均为115.5,铅组为121.3毫升/分钟/1.73平方米。口服蛋白质负荷后,对照组和铅暴露工人的肌酐清除率均显著增加(平均15%),这表明先前发现的尿类二十烷酸分泌变化显然对所检查的铅作业工人的肾脏血流动力学没有有害影响。

结论

铅作业工人的基线和刺激后的肌酐清除率不仅显著更高,而且与Pb-T呈正相关,这一发现表明适度的铅暴露可能与轻微的超滤状态有关,已发现这种状态可使与年龄相关的基线肌酐清除率下降减缓一半。尽管这种效应与工人健康的相关性尚不清楚,但可以得出结论,当大多数成年男性铅作业工人的血铅浓度定期保持在700微克铅/升以下时,不太可能发生不良肾脏变化。然而,由于对铅作业工人进行了入职前肾脏危险因素筛查,在将这一结论外推至一般人群时应谨慎。

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