巴比妥酸
犬尿氨酸
医学
黄脲酸
内科学
糖尿病
2型糖尿病
队列
内分泌学
肾脏疾病
危险系数
蛋白尿
犬尿氨酸途径
比例危险模型
肾功能
色氨酸
置信区间
生物
生物化学
敌手
氨基酸
受体
作者
Jing Liu,Jianhong Ching,Hai Ning Wee,Sylvia Liu,Resham L Gurung,Janus Lee,M Yiamunaa,Huili Zheng,Lye Siang Lee,Keven Ang,Yi Shao,Jean‐Paul Kovalik,Subramaniam Tavintharan,Chee Fang Sum,Kumar Sharma,Bryan Kestenbaum,Su Chi Lim
出处
期刊:Diabetes Care
[American Diabetes Association]
日期:2023-10-05
摘要
We sought to study the associations between plasma metabolites in the tryptophan-kynurenine pathway and the risk of progression to end-stage kidney disease (ESKD) in patients with type 2 diabetes.Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, and xanthurenic acid concentrations were measured in discovery (n = 1,915) and replication (n = 346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (n = 1,312). The primary outcome was a composite of incident ESKD (progression to estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, sustained dialysis, or renal death). The secondary outcome was annual eGFR decline.In the discovery cohort, tryptophan was inversely associated with risk for ESKD, and kynurenine-to-tryptophan ratio (KTR) was positively associated with risk for ESKD after adjustment for clinical risk factors, including baseline eGFR and albuminuria (adjusted hazard ratios [HRs] 0.62 [95% CI 0.51, 0.75] and 1.48 [1.20, 1.84] per 1 SD). High levels of kynurenic acid and xanthurenic acid were associated with low risks of ESKD (0.74 [0.60, 0.91] and 0.74 [0.60, 0.91]). Consistently, high levels of tryptophan, kynurenic acid, and xanthurenic acid were independently associated with a slower eGFR decline, while a high KTR was predictive of a faster eGFR decline. Similar outcomes were obtained in the replication cohort. Furthermore, the inverse association between kynurenic acid and risk of ESKD was externally validated in CRIC participants with diabetes (adjusted HR 0.78 [0.65, 0.93]).Accelerated catabolism of tryptophan in the kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward the kynurenic acid branch may potentially slow renal progression.
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