A metabolomics approach identified toxins associated with uremic symptoms in advanced chronic kidney disease.
A metabolomics approach identified toxins associated with uremic symptoms in advanced chronic kidney disease.
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DOI：
10.1016/j.kint.2021.10.035
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发表时间：
2022-03
影响因子：
19.6
通讯作者：
Shafi T
中科院分区：
文献类型：
--
作者：
Hu JR;Myint L;Levey AS;Coresh J;Inker LA;Grams ME;Guallar E;Hansen KD;Rhee EP;Shafi T
尿毒症症状在晚期慢性肾病患者中很常见，但引起这些症状的毒素尚不清楚。为了评估这一点，我们对报告尿毒症症状且有可用储存血清的肾脏疾病饮食改良（MDRD）参与者进行了随机化后12个月随访访视的横断面研究。我们通过液相色谱-串联质谱法定量了1，163种代谢物。对于每一个尿毒症症状，我们计算了一个分数，作为严重程度乘以症状出现的天数。我们使用经验贝叶斯推断的线性模型分析了个体症状评分与代谢物的相关性，并对多重比较进行了调整。在695名参与者中，平均测量的肾小球滤过率（mGFR）为28 mL/min/1.73 m2。在214名mGFR低于20 mL/min/1.73 m2（mGFR低于20亚组）的患者亚组中，尿毒症症状比整个组更常见。对于具有显著相关性的所有代谢物，全组和亚组的相关性方向一致。对于胃肠道症状（不良口味、食欲不振、恶心和呕吐），11种代谢物与症状相关。对于神经系统症状（警觉性降低、白天入睡、健忘、缺乏活力和精力、易疲劳/虚弱），7种代谢物与症状相关。在敏感性分析中，相关性一致。因此，我们的原理研究证明了代谢组学在了解与尿毒症症状相关的代谢途径方面的潜力。需要进行更大规模的、具有外部验证的前瞻性研究。
Uremic symptoms are common in patients with advanced chronic kidney disease, but the toxins that cause these symptoms are unknown. To evaluate this, we performed a cross-sectional study of the 12 month post-randomization follow-up visit of Modification of Diet in Renal Disease (MDRD) participants reporting uremic symptoms who also had available stored serum. We quantified 1,163 metabolites by liquid chromatography-tandem mass spectrometry. For each uremic symptom, we calculated a score as the severity multiplied by the number of days the symptom was experienced. We analyzed the associations of the individual symptom scores with metabolites using linear models with empirical Bayesian inference, adjusted for multiple comparisons. Among 695 participants, the mean measured glomerular filtration rate (mGFR) was 28 mL/min/1.73 m2. Uremic symptoms were more common in the subgroup of 214 patients with an mGFR under 20 mL/min/1.73 m2 (mGFR under 20 subgroup) than in the full group. For all metabolites with significant associations, the direction of the association was concordant in the full group and the subgroup. For gastrointestinal symptoms (bad taste, loss of appetite, nausea, and vomiting), eleven metabolites were associated with symptoms. For neurologic symptoms (decreased alertness, falling asleep during the day, forgetfulness, lack of pep and energy, tiring easily/weakness), seven metabolites were associated with symptoms. Associations were consistent across sensitivity analyses. Thus, our proof of principle study demonstrates the potential for metabolomics to understand metabolic pathways associated with uremic symptoms. Larger, prospective studies with external validation are needed.
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影响因子：
5.4
作者：
Kalim S;Clish CB;Wenger J;Elmariah S;Yeh RW;Deferio JJ;Pierce K;Deik A;Gerszten RE;Thadhani R;Rhee EP
通讯作者：
Rhee EP
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影响因子：
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作者：
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通讯作者：
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影响因子：
6.2
作者：
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通讯作者：
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