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血管生物标志物在肾脏病患者结局中的作用。

The Role of Vascular Biomarkers in Outcomes of Patients with Kidney Disease.

机构信息

Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, Connecticut, USA,

Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, Connecticut, USA.

出版信息

Nephron. 2023;147(12):778-781. doi: 10.1159/000533415. Epub 2023 Aug 23.

Abstract

BACKGROUND

Vascular biomarkers may explain the link between acute kidney injury (AKI) and poor long-term outcomes such as cardiovascular disease (CVD). Vessel injury is exceedingly common in AKI and contributes to the development of kidney fibrosis and CVD. As prominent determinants of vessel stability in the body, angiopoietins and other prominent vascular biomarkers may explain this biological link.

SUMMARY

Angiopoietin-1 (Angpt-1) promotes vessel stability by decreasing inflammation, apoptosis, and vessel permeability. By contrast, angiopoietin-2 (Angpt-2) blocks the binding of Angpt-1 to its receptor and thus contributes to vessel instability and permeability. Based on our findings, higher levels of Angpt-1 relative to Angpt-2 were strongly associated with less risk of kidney disease progression, heart failure, and death in hospitalized patients with AKI. In chronic kidney disease patients, it has been shown that endothelial damage in glomerular vasculature triggers Angpt-2 secretion, leading to poor outcomes such as CVD and mortality. Furthermore, in kidney transplant recipients, Angpt-2 levels significantly decrease after transplantation suggesting that transplantation may reduce Angpt-2 levels and decrease rates of poor outcomes. Other vascular health pathways - such as vascular endothelial growth factor and placental growth factor - were associated with improved rates of survival after cardiac surgery in participants with and without AKI.

KEY MESSAGES

Vascular health biomarkers provide actionable pathways for clinical intervention in reducing CVD and mortality for AKI patients. There is great need for future research that focuses on developing robust prognostic vascular biomarker panels in order to help identify high-risk AKI survivors who may benefit from targeted follow-up and therapy, with the intention to prevent kidney and cardiac complications.

摘要

背景

血管生物标志物可以解释急性肾损伤(AKI)与心血管疾病(CVD)等不良长期结局之间的联系。血管损伤在 AKI 中非常常见,是导致肾脏纤维化和 CVD 的原因之一。作为体内血管稳定性的主要决定因素,血管生成素和其他突出的血管生物标志物可能解释了这种生物学联系。

总结

血管生成素-1(Angpt-1)通过减少炎症、细胞凋亡和血管通透性来促进血管稳定性。相比之下,血管生成素-2(Angpt-2)阻断 Angpt-1 与其受体的结合,从而导致血管不稳定和通透性增加。根据我们的发现,Angpt-1 相对于 Angpt-2 的水平较高与 AKI 住院患者的肾脏疾病进展、心力衰竭和死亡风险降低密切相关。在慢性肾脏病患者中,已经表明肾小球血管内皮损伤会触发 Angpt-2 的分泌,导致 CVD 和死亡率等不良结局。此外,在肾移植受者中,移植后 Angpt-2 水平显著下降,这表明移植可能降低 Angpt-2 水平并降低不良结局的发生率。其他血管健康途径 - 如血管内皮生长因子和胎盘生长因子 - 与 AKI 患者和无 AKI 患者心脏手术后的生存率提高相关。

关键信息

血管健康生物标志物为临床干预提供了可行的途径,以降低 AKI 患者的 CVD 和死亡率。未来需要更多的研究来专注于开发强大的预后血管生物标志物组合,以帮助识别可能受益于针对性随访和治疗的高危 AKI 幸存者,从而预防肾脏和心脏并发症。

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