作为急性肾衰竭预后标志物的白细胞介素-6及其依赖性上调作用

IF 2 4区 医学 Q2 UROLOGY & NEPHROLOGY
Laura González-Lafuente , Elisa Mercado-García , Sara Vázquez-Sánchez , Daniel González-Moreno , Lisardo Boscá , María Fernández-Velasco , Julián Segura , Makoto Kuro-O , Luis M. Ruilope , Fernando Liaño , Gema Ruiz-Hurtado
{"title":"作为急性肾衰竭预后标志物的白细胞介素-6及其依赖性上调作用","authors":"Laura González-Lafuente ,&nbsp;Elisa Mercado-García ,&nbsp;Sara Vázquez-Sánchez ,&nbsp;Daniel González-Moreno ,&nbsp;Lisardo Boscá ,&nbsp;María Fernández-Velasco ,&nbsp;Julián Segura ,&nbsp;Makoto Kuro-O ,&nbsp;Luis M. Ruilope ,&nbsp;Fernando Liaño ,&nbsp;Gema Ruiz-Hurtado","doi":"10.1016/j.nefro.2024.04.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and objective</h3><div>In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI.</div></div><div><h3>Materials and methods</h3><div>Plasma levels of IL-6, klotho and FGF23 were analysed in samples from 28 patients with AKI and related to renal function on hospital admission, and after 24 and 72<!--> <!-->hours. In addition, the predictive capacity of IL-6 on AKI-associated mortality was analysed at the three study time points. In an experimental nephrotoxic -AKI mouse model, systemic IL-6 and FGF23 values were also analysed 24 and 72<!--> <!-->hours after induction of kidney damage, as well as in mice overexpressing the anti-ageing protein, klotho.</div></div><div><h3>Results</h3><div>Systemic IL-6 levels increased in AKI patients, especially in hospital admission time, and decreased in parallel with improving renal function. At the same time as IL-6 values increased, there was an increase in FGF23 and a decrease in klotho levels, with a significant and positive correlation between IL-6 and FGF23 levels. In addition, we obtained that systemic IL-6 levels were a good predictor of mortality in these patients, with an area under the curve equal to one at 72<!--> <!-->hours after AKI. In the experimental mouse AKI model, we also observed an increase in plasma levels in both IL-6 and FGF23 after 24<!--> <!-->hours of kidney damage. Nevertheless, in transgenic mice overexpressing klotho, there was no such increase in any of them.</div></div><div><h3>Conclusions</h3><div>There is an association between renal damage and increased levels of IL-6 and FGF23 in patients with AKI, especially on hospital admission time. Moreover, IL-6 levels are able to predict mortality in these patients, being a promising prognostic biomarker at any study time with a strong prediction at 72<!--> <!-->hours after patient admission. Maintaining adequate klotho levels could prevent the IL-6 mediated inflammatory response and therefore also reduce the degree and severity of renal damage after AKI.</div></div>","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"44 6","pages":"Pages 818-829"},"PeriodicalIF":2.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interleuquina-6 como marcador pronóstico en el fracaso renal agudo y su regulación dependiente de klotho\",\"authors\":\"Laura González-Lafuente ,&nbsp;Elisa Mercado-García ,&nbsp;Sara Vázquez-Sánchez ,&nbsp;Daniel González-Moreno ,&nbsp;Lisardo Boscá ,&nbsp;María Fernández-Velasco ,&nbsp;Julián Segura ,&nbsp;Makoto Kuro-O ,&nbsp;Luis M. Ruilope ,&nbsp;Fernando Liaño ,&nbsp;Gema Ruiz-Hurtado\",\"doi\":\"10.1016/j.nefro.2024.04.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and objective</h3><div>In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI.</div></div><div><h3>Materials and methods</h3><div>Plasma levels of IL-6, klotho and FGF23 were analysed in samples from 28 patients with AKI and related to renal function on hospital admission, and after 24 and 72<!--> <!-->hours. In addition, the predictive capacity of IL-6 on AKI-associated mortality was analysed at the three study time points. In an experimental nephrotoxic -AKI mouse model, systemic IL-6 and FGF23 values were also analysed 24 and 72<!--> <!-->hours after induction of kidney damage, as well as in mice overexpressing the anti-ageing protein, klotho.</div></div><div><h3>Results</h3><div>Systemic IL-6 levels increased in AKI patients, especially in hospital admission time, and decreased in parallel with improving renal function. At the same time as IL-6 values increased, there was an increase in FGF23 and a decrease in klotho levels, with a significant and positive correlation between IL-6 and FGF23 levels. In addition, we obtained that systemic IL-6 levels were a good predictor of mortality in these patients, with an area under the curve equal to one at 72<!--> <!-->hours after AKI. In the experimental mouse AKI model, we also observed an increase in plasma levels in both IL-6 and FGF23 after 24<!--> <!-->hours of kidney damage. Nevertheless, in transgenic mice overexpressing klotho, there was no such increase in any of them.</div></div><div><h3>Conclusions</h3><div>There is an association between renal damage and increased levels of IL-6 and FGF23 in patients with AKI, especially on hospital admission time. Moreover, IL-6 levels are able to predict mortality in these patients, being a promising prognostic biomarker at any study time with a strong prediction at 72<!--> <!-->hours after patient admission. Maintaining adequate klotho levels could prevent the IL-6 mediated inflammatory response and therefore also reduce the degree and severity of renal damage after AKI.</div></div>\",\"PeriodicalId\":18997,\"journal\":{\"name\":\"Nefrologia\",\"volume\":\"44 6\",\"pages\":\"Pages 818-829\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nefrologia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0211699524000353\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nefrologia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0211699524000353","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景和目的在急性肾损伤(AKI)中,肾损伤会激活强烈的炎症成分,而这一过程背后的主要介质之一是促炎性白细胞介素 6 或 IL-6。除此现象外,矿物质代谢的不同成分也发生了改变,如依赖成纤维细胞生长因子(FGF)23 和抗衰老辅助因子 klotho 的成分。本研究旨在探讨 AKI 早期肾功能与 IL-6、FGF23 和 klotho 系统水平之间的关系,分析 IL-6 对与 AKI 相关的早期死亡率的预测能力。材料与方法分析了 28 名 AKI 患者样本中的 IL-6、klotho 和 FGF23 的血浆水平,以及入院时、24 小时后和 72 小时后与肾功能的关系。此外,还分析了 IL-6 在三个研究时间点对 AKI 相关死亡率的预测能力。在实验性肾毒性 AKI 小鼠模型中,还分析了诱导肾损伤 24 小时和 72 小时后的全身 IL-6 和 FGF23 值,以及过度表达抗衰老蛋白 klotho 的小鼠的 IL-6 值。在 IL-6 水平升高的同时,FGF23 水平升高,klotho 水平下降,IL-6 和 FGF23 水平之间存在显著的正相关。此外,我们还发现,全身 IL-6 水平能很好地预测这些患者的死亡率,AKI 后 72 小时的曲线下面积等于 1。在实验性小鼠 AKI 模型中,我们也观察到肾脏损伤 24 小时后血浆中 IL-6 和 FGF23 的水平都有所上升。结论肾损伤与 AKI 患者 IL-6 和 FGF23 水平升高有关,尤其是在入院时。此外,IL-6 水平还能预测这些患者的死亡率,在任何研究时间都是一种有希望的预后生物标志物,在患者入院后 72 小时内具有很强的预测作用。保持足够的 klotho 水平可以防止 IL-6 介导的炎症反应,从而减轻 AKI 后肾损伤的程度和严重性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interleuquina-6 como marcador pronóstico en el fracaso renal agudo y su regulación dependiente de klotho

Background and objective

In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI.

Materials and methods

Plasma levels of IL-6, klotho and FGF23 were analysed in samples from 28 patients with AKI and related to renal function on hospital admission, and after 24 and 72 hours. In addition, the predictive capacity of IL-6 on AKI-associated mortality was analysed at the three study time points. In an experimental nephrotoxic -AKI mouse model, systemic IL-6 and FGF23 values were also analysed 24 and 72 hours after induction of kidney damage, as well as in mice overexpressing the anti-ageing protein, klotho.

Results

Systemic IL-6 levels increased in AKI patients, especially in hospital admission time, and decreased in parallel with improving renal function. At the same time as IL-6 values increased, there was an increase in FGF23 and a decrease in klotho levels, with a significant and positive correlation between IL-6 and FGF23 levels. In addition, we obtained that systemic IL-6 levels were a good predictor of mortality in these patients, with an area under the curve equal to one at 72 hours after AKI. In the experimental mouse AKI model, we also observed an increase in plasma levels in both IL-6 and FGF23 after 24 hours of kidney damage. Nevertheless, in transgenic mice overexpressing klotho, there was no such increase in any of them.

Conclusions

There is an association between renal damage and increased levels of IL-6 and FGF23 in patients with AKI, especially on hospital admission time. Moreover, IL-6 levels are able to predict mortality in these patients, being a promising prognostic biomarker at any study time with a strong prediction at 72 hours after patient admission. Maintaining adequate klotho levels could prevent the IL-6 mediated inflammatory response and therefore also reduce the degree and severity of renal damage after AKI.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Nefrologia
Nefrologia 医学-泌尿学与肾脏学
CiteScore
3.40
自引率
7.70%
发文量
148
审稿时长
47 days
期刊介绍: Nefrología is the official publication of the Spanish Society of Nephrology. The Journal publishes articles on basic or clinical research relating to nephrology, arterial hypertension, dialysis and kidney transplants. It is governed by the peer review system and all original papers are subject to internal assessment and external reviews. The journal accepts submissions of articles in English and in Spanish languages.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信