Immundiagnostik AG, Bensheim, Germany,
Department of Cardiology and Angiology, Campus Mitte, Charité University Medicine Berlin, Berlin, Germany,
Kidney Blood Press Res. 2019;44(4):765-776. doi: 10.1159/000501483. Epub 2019 Aug 6.
Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events.
It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF).
We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay.
In the CHF cohort, both kynurenine and NT-proBNP increased with NYHA class. Univariate binary logistic regression showed kynurenine to predict death within a 6-month follow-up (OR 1.43, 95% CI 1.03-2.00, p = 0.033) whereas NT-proBNP did not contribute significantly. Kynurenine, like NT-proBNP, was able to discriminate at a 30% threshold of left ventricular ejection fraction (LVEF; AUC-ROC, both 0.74). Kynurenine correlated inversely with LVEF (ϱ = -0.394), glomerular filtration fraction (GFR; ϱ = -0.615), and peak VO2 (ϱ = -0.626). Moreover, there was a strong correlation of kynurenine with NT-proBNP (ϱ = 0.615). In the AICD cohort, multiple linear regression analysis demonstrated highly significant associations of kynurenine with GFR, hsCRP, and tryptophan, as well as a significant impact of age.
This work speaks in favor of kynurenine being a new and valuable biomarker of CHF, with particular attention placed on its ability to predict mortality and reflect exercise capacity.
犬尿氨酸是色氨酸途径的代谢产物，在神经炎症、癌症免疫学和心血管炎症中发挥关键作用，并已被证明可预测心血管事件。
本研究旨在增加犬尿氨酸作为慢性心力衰竭（CHF）生物标志物价值的数据量。
我们研究了 CHF 队列（CHF，n=114）中血浆犬尿氨酸的预测价值；在患有 CHF 的除颤器携带者的第二个队列（AICD，n=156）中，我们通过酶免疫分析法确定了该标志物的临床和生化决定因素。
在 CHF 队列中，犬尿氨酸和 NT-proBNP 均随 NYHA 分级而增加。单因素二元逻辑回归显示，犬尿氨酸可预测 6 个月随访内的死亡（OR 1.43，95%CI 1.03-2.00，p=0.033），而 NT-proBNP 则无显著作用。犬尿氨酸与 NT-proBNP 一样，能够在左心室射血分数（LVEF）30%的阈值下区分（AUC-ROC，两者均为 0.74）。犬尿氨酸与 LVEF 呈负相关（ρ=-0.394），与肾小球滤过分数（GFR；ρ=-0.615）和峰值 VO2（ρ=-0.626）呈负相关。此外，犬尿氨酸与 NT-proBNP 之间存在很强的相关性（ρ=0.615）。在 AICD 队列中，多元线性回归分析表明，犬尿氨酸与 GFR、hsCRP 和色氨酸高度相关，且年龄有显著影响。
本研究支持犬尿氨酸作为 CHF 的一种新的有价值的生物标志物，特别关注其预测死亡率和反映运动能力的能力。
