Tryptophan levels associate with incident cardiovascular disease in chronic kidney disease.
Tryptophan levels associate with incident cardiovascular disease in chronic kidney disease.
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DOI：
10.1093/ckj/sfaa031
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发表时间：
2021-04
影响因子：
4.6
通讯作者：
Michigan Kidney Translational Core CPROBE Investigator Group
中科院分区：
文献类型：
--
作者：
Konje VC;Rajendiran TM;Bellovich K;Gadegbeku CA;Gipson DS;Afshinnia F;Mathew AV;Michigan Kidney Translational Core CPROBE Investigator Group
炎症和氧化应激等非传统危险因素在慢性肾脏疾病（CKD）中普遍存在的心血管疾病（CVD）风险增加中起重要作用。色氨酸分解代谢通过犬尿氨酸途径（KP）与全身炎症和心血管疾病在一般和透析人群。然而，在CKD人群中KP与CVD的关系尚不清楚。我们使用靶向质谱法测量了92例有CVD病史（老年性CVD）患者的色氨酸代谢物；随访期间无CVD病史及新发CVD患者46例（无CVD）；46例无CVD病史的患者在中位随访2年期间发生CVD（事件CVD）。三组患者在年龄、性别、种族、糖尿病状态和CKD分期方面均吻合良好，仅在总胆固醇和蛋白尿方面存在差异。与无CVD或老CVD组相比，“突发CVD”患者的色氨酸和犬尿氨酸水平显著降低（P = 5.2E-7; P = 0.003）。犬尿氨酸、3-羟基犬尿氨酸、犬尿氨酸均随CKD分期加重而升高（P < 0.05）。基线色氨酸水平的增加与无CVD组相比，即使在调整经典CVD危险因素后，CVD发生率降低0.32倍（P = 0.000014）。在使用基线临床变量预测CVD事件的判别分析构建的受试者工作曲线上添加色氨酸和犬尿氨酸水平，使曲线下面积从0.76增加到0.82 （P = 0.04）。总之，我们的研究表明，低色氨酸水平与CKD中CVD的发生有关。
Non-traditional risk factors like inflammation and oxidative stress play an essential role in the increased cardiovascular disease (CVD) risk prevalent in chronic kidney disease (CKD). Tryptophan catabolism by the kynurenine pathway (KP) is linked to systemic inflammation and CVD in the general and dialysis population. However, the relationship of KP to incident CVD in the CKD population is unknown. We measured tryptophan metabolites using targeted mass spectrometry in 92 patients with a history of CVD (old CVD); 46 patients with no history of CVD and new CVD during follow-up (no CVD); and 46 patients with no CVD history who developed CVD in the median follow-up period of 2 years (incident CVD). The three groups are well-matched in age, gender, race, diabetes status and CKD stage, and only differed in total cholesterol and proteinuria. Tryptophan and kynurenine levels significantly decreased in patients with ‘Incident CVD’ compared with the no CVD or old CVD groups (P = 5.2E–7; P = 0.003 respectively). Kynurenic acid, 3-hydroxykynurenine and kynurenine are all increased with worsening CKD stage (P < 0.05). An increase in tryptophan levels at baseline was associated with 0.32-fold lower odds of incident CVD (P = 0.000014) compared with the no CVD group even after adjustment for classic CVD risk factors. Addition of tryptophan and kynurenine levels to the receiver operating curve constructed from discriminant analysis predicting incident CVD using baseline clinical variables increased the area under the curve from 0.76 to 0.82 (P = 0.04). In summary, our study demonstrates that low tryptophan levels are associated with incident CVD in CKD.
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DOI：
10.1177/1178646917694600
发表时间：
2017
期刊：
International journal of tryptophan research : IJTR
影响因子：
--
作者：
Debnath S;Velagapudi C;Redus L;Thameem F;Kasinath B;Hura CE;Lorenzo C;Abboud HE;O'Connor JC
通讯作者：
O'Connor JC
影响因子：
4
作者：
Badawy AA
通讯作者：
Badawy AA
影响因子：
2.8
作者：
Pawlak, Krystyna;Kowalewska, Anna;Pawlak, Dariusz
通讯作者：
Pawlak, Dariusz
影响因子：
5.3
作者：
Pawlak, Krystyna;Brzosko, Szymon;Pawlak, Dariusz
通讯作者：
Pawlak, Dariusz
影响因子：
2.7
作者：
Fujigaki, Hidetsugu;Saito, Kuniaki;Seishima, Mitsuru
通讯作者：
Seishima, Mitsuru