Pigmentation Markers: More Color in the Picture of Uremic Toxicity?
Pigmentation Markers: More Color in the Picture of Uremic Toxicity?
复制标题
色素沉着标记：尿毒症毒性图片中的更多颜色？
作者：
R. Vanholder;G. Glorieux;I. Devolder;S. Van Laecke
Murakami 等人报告的结果。 [4] 应谨慎考虑，因为它们仅基于 16 名血液透析患者，因此需要确认；值得注意的是，其中 6 名患者是糖尿病患者，与非糖尿病慢性肾衰竭患者相比，他们所遭受的氧化应激程度呈指数级增长。这是一个值得关注的问题，因为他们文章中描述的大多数溶质都是氧化修饰的结果。因此，当研究更多人群的这些溶质浓度时，将糖尿病患者与非糖尿病患者进行比较会很有趣。除了它们与黑色素瘤 [7] 以及皮肤和头发色素沉着 [8, 9] 的联系外，关于这些色素沉着标记物的临床和生化意义的信息很少，但 Murakami 等人的文章中提到的一些特征。 [4] 尽管如此，还是引人注目的，特别是对于那些对尿毒症毒性和对抗这种疾病的治疗选择感兴趣的人。基本上，我想到了四种想法。首先，作为酪氨酸的代谢产物，这些分子与其他组的尿毒症潴留化合物有家族联系，其中大多数是酚类，它们也源自酪氨酸[10]。此外，真黑色素与二羟基吲哚[11]的结构相似性也表明与另一组重要的尿毒症潴留溶质——吲哚——的联系。所有这些类别的分子的共同特征是它们的蛋白质结合以及通过标准透析疗法去除它们的困难。肾衰竭期间溶质的滞留导致了复杂的积累模式。 2003年，欧洲尿毒症毒素工作组将同行评审文献中描述的尿毒症化合物制成表格，总共列出了90种不同的化合物[1]。与此同时，还鉴定出了其他几种化合物 [2] ，通过蛋白质组分析获得的结果描述了血液透析患者超滤液中 1,000 多种分子量为 1 800 Da 的肽类化合物 [3] ，这表明我们目前所了解的实际上只是冰山一角。为了能够识别毒性途径并制定去除相关有毒溶质或抵消其代谢影响的治疗策略，有关尿毒症潴留的知识必须尽可能完整。在本期《血液净化》中，Murakami 等人将以前不为人知的滞留溶质色素沉着标记物或黑色素作为一组新的尿毒症化合物添加到现有的已知尿毒症毒素列表中 [1]。 [4] .同时，作者提供了与尿毒症综合征最有趣但解释不充分的副现象之一相关的信息：许多慢性肾病患者都患有色素沉着过度 [5, 6] 。最近的肾脏病学文献实际上没有关注这个问题。在线发布：2007 年 12 月 17 日
The results reported by Murakami et al. [4] should be considered with care as they are based on only 16 hemodialysis patients and, therefore, need confirmation; of note, 6 of these patients were diabetics, who are known to suffer from an exponential degree of oxidative stress as compared to non-diabetic chronic kidney failure patients. This is a matter of concern since most of the solutes depicted in their article are the result of oxidative modifications. For this reason, when larger populations are studied for the concentration of these solutes, it would be interesting to compare diabetics with non-diabetics. Apart from their link to melanoma [7] and skin and hair pigmentation [8, 9] , there is only scant information about the clinical and biochemical significance of these pigmentation markers, but a number of features referred to in the article by Murakami et al. [4] are nevertheless striking, especially for those interested in uremic toxicity and the therapeutic options for fighting this condition. Basically, four reflections come to mind. First, as metabolites of tyrosine, these molecules have family ties with other groups of uremic retention compounds, most of all the phenols, which also originate from tyrosine [10] . In addition, the structural similitude of eumelanin with dihydroxyindole [11] also suggests a tie with another group of important uremic retention solutes, the indoles. Common features of all these categories of molecules are their protein binding and the difficulty of removing them by standard dialysis therapies. The retention of solutes during kidney failure gives rise to a complex pattern of accumulation. In 2003, the uremic compounds which until then had been described in the peer-reviewed literature were tabulated by the European Uremic Toxin Work Group and a total number of 90 different compounds were listed [1] . In the meantime, several other compounds have been identified [2] , and the results obtained with proteome analysis, describing more than 1,000 peptidic compounds with a molecular weight of 1 800 Da, in ultrafiltrates from hemodialysis patients [3] infer that what we currently know in fact reveals only the tip of the iceberg. To enable the identification of toxicity pathways and to develop therapeutic strategies for the removal of relevant toxic solutes or to counteract their metabolic effects, knowledge on uremic retention must be as complete as possible. In this issue of Blood Purification, pigmentation markers or melanins, previously unknown as retention solutes, are added as a new set of uremic compounds to the existing list of known uremic toxins [1] by Murakami et al. [4] . At the same time the authors offer information related to one of the most intriguing but insufficiently explained epiphenomena of the uremic syndrome: hyperpigmentation from which many patients with chronic kidney disease suffer [5, 6] . Recent nephrological literature pays virtually no attention to this problem. Published online: December 17, 2007
DOI：
10.1073/pnas.0403994101
发表时间：
2004-10-19
影响因子：
11.1
作者：
Takeuchi, S;Zhang, WG;Brash, DE
通讯作者：
Brash, DE