The toxins that contribute to uremic symptoms in patients with chronic kidney disease (CKD) are unknown. We sought to apply complementary statistical modeling approaches to data from untargeted plasma metabolomic profiling to identify solutes associated with uremic symptoms in patients with CKD. Cross-sectional. 1,761 Chronic Renal Insufficiency Cohort (CRIC) participants with CKD not treated with dialysis. Measurement of 448 known plasma metabolites. The uremic symptoms of fatigue, anorexia, pruritus, nausea, paresthesia, and pain were assessed by single items on the Kidney Disease Quality of Life-36 instrument. Multivariable adjusted linear regression, least absolute shrinkage and selection operator linear regression, and random forest models were used to identify metabolites associated with symptom severity. After adjustment for multiple comparisons, metabolites selected in at least 2 of the 3 modeling approaches were deemed “overall significant.” Participant mean estimated glomerular filtration rate was 43mL/min/1.73m, with 44% self-identifying as female and 41% as non-Hispanic Black. The prevalence of uremic symptoms ranged from 22% to 55%. We identified 17 metabolites for which a higher level was associated with greater severity of at least one uremic symptom and 9 metabolites inversely associated with uremic symptom severity. Many of these metabolites exhibited at least a moderate correlation with estimated glomerular filtration rate (Pearson’s ≥0.5), and some were also associated with the risk of developing kidney failure or death in multivariable adjusted Cox regression models. Lack of a second independent cohort for external validation of our findings. Metabolomic profiling was used to identify multiple solutes associated with uremic symptoms in adults with CKD, but future validation and mechanistic studies are needed. Individuals living with chronic kidney disease (CKD) often experience symptoms related to CKD, traditionally called uremic symptoms. It is likely that CKD results in alterations in the levels of numerous circulating substances that, in turn, cause uremic symptoms; however, the identity of these solutes is not known. In this study, we used metabolomic profiling in patients with CKD to gain insights into the pathophysiology of uremic symptoms. We identified 26 metabolites whose levels were significantly associated with at least one of the symptoms of fatigue, anorexia, itchiness, nausea, paresthesia, and pain. The results of this study lay the groundwork for future research into the biological causes of symptoms in patients with CKD.

中文翻译：

---

与 CKD 患者尿毒症症状相关的代谢物：慢性肾功能不全队列 (CRIC) 研究的结果

导致慢性肾病 (CKD) 患者出现尿毒症症状的毒素尚不清楚。我们试图将补充统计模型方法应用于来自非靶向血浆代谢组学分析的数据，以识别与 CKD 患者尿毒症症状相关的溶质。横截面。 1,761 名慢性肾功能不全队列 (CRIC) 患有 CKD 的参与者未接受透析治疗。测量 448 种已知血浆代谢物。疲劳、厌食、瘙痒、恶心、感觉异常和疼痛等尿毒症症状通过肾脏疾病生活质量36仪器的单项进行评估。使用多变量调整线性回归、最小绝对收缩和选择算子线性回归以及随机森林模型来识别与症状严重程度相关的代谢物。经过多重比较调整后，3 种建模方法中至少有 2 种选择的代谢物被认为“总体显着”。参与者平均估计肾小球滤过率为 43mL/min/1.73m，其中 44% 的人自认为是女性，41% 的人自认为是非西班牙裔黑人。尿毒症症状的患病率为22%至55%。我们确定了 17 种代谢物，其中较高水平与至少一种尿毒症症状的严重程度相关，而 9 种代谢物与尿毒症症状严重程度呈负相关。其中许多代谢物与估计的肾小球滤过率至少表现出中等相关性（Pearson ≥0.5），并且在多变量调整的 Cox 回归模型中，一些代谢物还与发生肾衰竭或死亡的风险相关。缺乏第二个独立队列来对我们的研究结果进行外部验证。代谢组学分析用于识别与 CKD 成人尿毒症症状相关的多种溶质，但需要未来的验证和机制研究。慢性肾脏病 (CKD) 患者经常会出现与 CKD 相关的症状，传统上称为尿毒症症状。 CKD 可能会导致多种循环物质水平发生变化，进而导致尿毒症症状；然而，这些溶质的身份尚不清楚。在这项研究中，我们使用 CKD 患者的代谢组学分析来深入了解尿毒症症状的病理生理学。我们鉴定出 26 种代谢物，其水平与疲劳、厌食、瘙痒、恶心、感觉异常和疼痛中的至少一种症状显着相关。这项研究的结果为未来研究 CKD 患者症状的生物学原因奠定了基础。