The Department of Medicine, Stanford University, Palo Alto, California, United States of America.
The Department of Medicine, VA Palo Alto Healthcare System, Palo Alto, California, United States of America.
PLoS One. 2021 Feb 12;16(2):e0246765. doi: 10.1371/journal.pone.0246765. eCollection 2021.
Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform's chemical library. A role for uremic solutes in pruritus remains to be established.
瘙痒是血液透析患者常见的一种使人虚弱的症状。由于尿毒症瘙痒的原因尚不清楚，因此治疗很困难。本研究提出了一个假设，即瘙痒是由肾脏衰竭时在血浆中积聚的溶质引起的。我们试图通过代谢组学分析来确定导致尿毒症瘙痒的溶质，方法是比较严重瘙痒与轻度/无瘙痒的血液透析患者的血浆。使用 100 毫米视觉模拟量表（VAS）评估血液透析患者的瘙痒严重程度，严重瘙痒定义为>70 毫米，轻度/无瘙痒定义为<10 毫米。纳入了 12 例严重瘙痒（瘙痒）患者和 24 例轻度/无瘙痒（无瘙痒）患者。使用成熟的代谢组学平台（Metabolon，Inc.）分析预处理血浆和血浆超滤液。为了确定与瘙痒相关的溶质，我们使用错误发现率（q 值）和主成分分析比较瘙痒患者和无瘙痒患者的每个溶质的平均峰面积。瘙痒患者和无瘙痒患者的透析龄、Kt/Vurea 以及血清钙、磷、PTH、白蛋白、铁蛋白和血红蛋白水平相似。代谢组学分析鉴定出 1548 种溶质，其中 609 种被归类为尿毒症溶质。在瘙痒患者和无瘙痒患者的血浆或血浆超滤液中，没有发现任何溶质或溶质组的水平存在差异。血液透析患者的代谢组学分析未发现任何与瘙痒相关的溶质。代谢组学分析的局限性在于，感兴趣的溶质可能不在代谢组学平台的化学库中。尿毒症溶质在瘙痒中的作用仍有待确定。
