Interleukin-6 as a prognostic marker in acute kidney injury and its klotho-dependent regulation.

Autor:	González-Lafuente L; Laboratorio Traslacional Cardiorrenal, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain., Mercado-García E; Laboratorio Traslacional Cardiorrenal, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain., Vázquez-Sánchez S; Laboratorio Traslacional Cardiorrenal, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain., González-Moreno D; Laboratorio Traslacional Cardiorrenal, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain., Boscá L; Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, Madrid, Spain., Fernández-Velasco M; Grupo de Cardiología Clínica e Invasiva, Instituto de Investigación Sanitaria del Hospital La Paz (IdiPAZ), Hospital Universitario La Paz, Madrid; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación del Hospital La Paz, IdiPaz, Madrid, Spain., Segura J; Laboratorio Traslacional Cardiorrenal, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain; Servicio de Nefrología, Unidad de Hipertensión, Hospital Universitario 12 de Octubre, Madrid, Spain., Kuro-O M; Division of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Ruilope LM; Laboratorio Traslacional Cardiorrenal, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain; Escuela de Estudios de Doctorado e Investigación, Universidad Europea de Madrid, Madrid, Spain., Liaño F; Instituto Ramón y Cajal de Investigación Sanitaria (IRyCis), Madrid, Spain., Ruiz-Hurtado G; Laboratorio Traslacional Cardiorrenal, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain; Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: gemaruiz@h12o.es.
Jazyk:	angličtina
Zdroj:	Nefrologia [Nefrologia (Engl Ed)] 2024 Nov-Dec; Vol. 44 (6), pp. 818-829. Date of Electronic Publication: 2024 Nov 29.
DOI:	10.1016/j.nefroe.2024.11.010
Abstrakt:	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. Material 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 h. 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 h 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 h after AKI. In the experimental mouse AKI model, we also observed an increase in plasma levels in both IL-6 and FGF23 after 24 h 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 h 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. Competing Interests: Declaration of competing interest The authors of this paper have no conflicts of interest to declare. (Copyright © 2024 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)
Databáze:	MEDLINE
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