慢性肾功能不全的铝毒性

John Savory, Roger L. Bertholf, Michael R. Wills
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引用次数: 20

摘要

铝是环境中普遍存在的元素,已被证明是有毒的,特别是对肾功能受损的个体。人们对铝的生物化学及其毒性作用机制知之甚少。大多数对铝的兴趣一直在血液透析单位的临床设置。在这里,铝中毒是由于透析液的污染,以及用含铝磷酸盐结合凝胶治疗患者而发生的。铝已被证明是透析性脑病综合征和透析性骨营养不良的骨软化成分的主要贡献者。与铝毒性相关的其他临床症状有小细胞贫血和转移性骨外钙化。去铁胺和血液透析配合治疗可有效治疗铝超载。在血液透析过程中,铝很容易从透析液转移到患者的血液中。一旦转移,铝与不可透析的等离子体成分紧密结合。建议透析液铝的浓度极低,在10-15 μg/l范围内,以防止毒性作用。很少有针对分离结合铝的各种等离子体的研究。凝胶过滤色谱法鉴定了5个主要的组分,其中一个是低分子量的,其他的似乎是蛋白质-铝复合物。关于铝监测的建议已经公布,并提供了“安全”和有毒浓度。此外,监测的频率也已得到解决。铝的分析方法存在的主要问题是由于技术不准确和污染困难。最广泛使用的分析技术是电热原子吸收光谱法,它可以在细心的分析人员手中提供可靠的测量结果。
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8 Aluminium toxicity in chronic renal insufficiency

Aluminium is a ubiquitous element in the environment and has been demonstrated to be toxic, especially in individuals with impaired renal function. Not much is known about the biochemistry of aluminium and the mechanisms of its toxic effects. Most of the interest in aluminium has been in the clinical setting of the haemodialysis unit. Here aluminium toxicity occurs due to contamination of dialysis solutions, and treatment of the patients with aluminium-containing phosphate binding gels. Aluminium has been shown to be the major contributor to the dialysis encephalopathy syndrome and an osteomalacic component of dialysis osteodystrophy. Other clinical disturbances associated with aluminium toxicity are a microcytic anaemia and metastatic extraskeletal calcification. Aluminium overload can be treated effectively by chelation therapy with desferrioxamine and haemodialysis.

Aluminium is readily transferred from the dialysate to the patient's bloodstream during haemodialysis. Once transferred, the aluminium is tightly bound to non-dialysable plasma constituents. Very low concentrations of dialysate aluminium in the range of 10–15 μg/l are recommended to guard against toxic effects. Very few studies have been directed towards the separation of the various plasma species which bind aluminium. Gel filtration chromatography has been used to identify five major fractions, one of which is of low molecular weight and the others appear to be protein-aluminium complexes. Recommendations on aluminium monitoring have been published and provide ‘safe’ and toxic concentrations. Also, the frequency of monitoring has been addressed.

Major problems exist with the analytical methods for measuring aluminium which result from inaccurate techniques and contamination difficulties. The most widely used analytical technique is electrothermal atomic absorption spectrometry which can provide reliable measurements in the hands of a careful analyst.

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