Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers.
Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers.
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DOI：
10.1177/1178646917694600
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
O'Connor JC
中科院分区：
文献类型：
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作者：
Debnath S;Velagapudi C;Redus L;Thameem F;Kasinath B;Hura CE;Lorenzo C;Abboud HE;O'Connor JC
2型糖尿病（T2D）是慢性肾脏疾病（CKD）的主要病例。炎症与T2D和CKD患者的代谢失调有关。色氨酸（TRP）代谢可能与CKD结局和相关症状有关。我们研究了T2D和CKD患者TRP代谢与炎症标志物的关系。数据收集自具有良好特征的2型糖尿病患者CKD的所有阶段，包括血液透析患者。检测血浆中关键TRP代谢物（犬尿氨酸[KYN]、犬尿酸[KYNA]、喹啉酸[QA]）、促炎因子（肿瘤坏死因子-α [TNF-α]、白细胞介素-6 [IL-6]）、c反应蛋白。KYN/TRP比值作为吲哚胺2,3-双加氧酶1 （IDO1）酶活性的替代指标。循环TRP水平与CKD分期呈显著负相关（P < 0.0001）。下游生物活性TRP代谢物KYN、KYNA和QA与肾脏疾病的严重程度呈正相关（P < 0.0001）。在多元线性回归中，在调整估计的肾小球滤过率（eGFR）后，TNF-α和IL-6都与KYN/TRP比值无关。在考虑eGFR的影响后，只有TNF-α与KYN独立相关。继发于T2D的慢性肾脏疾病可能与炎症和肾功能受损引起的毒性TRP代谢物的积累有关。未来有必要进行纵向研究，以确定KYN的积累是否直接导致T2D患者的CKD进展和相关症状。
Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA]), proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity. There was a significant inverse association between circulating TRP level and stages of CKD (P < 0.0001). Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease (P < 0.0001). In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR). Only TNF-α was independently related to KYN after taking into account the effect of eGFR. Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.