Systemic inflammatory profiles are associated with long-term kidney failure and patient mortality in chronic kidney disease
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Chronic kidney disease (CKD) is frequently associated with systemic inflammation. However, the relationship between inflammatory cytokines and CKD progression remains incompletely understood. Methods: The PROGRESER study (Factores de PROGRESion en Enfermedad Renal) was a multicentre, prospective observational cohort that included patients with CKD stage G3. A total of 17 plasma and 10 urinary inflammatory cytokines were measured in 165 participants, at baseline, 18 months and 36 months, using a fully automated HISCL immune analyser. Unsupervised cluster analysis identified six distinct patient clusters. Associations between cytokine levels and kidney outcomes [estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (uACR), KDIGO risk scores, kidney replacement therapy (KRT)], cardiovascular outcomes (cardiovascular hospitalization) and death was assessed during a follow-up of up to 10 years. The primary outcome was a combination of KRT or death. Results: Plasma levels of 15 cytokines and 6 urinary cytokines differed between patients with CKD and 30 healthy controls. Of these, plasma interleukin (IL)-8 levels were inversely associated with uACR slopes, while IL-22, tumour necrosis factor (TNF)-α and Growth Differentiation Factor 15 (GDF-15) levels showed positive correlations with uACR progression. Additionally, plasma TNF-α and GDF-15 were associated with KRT and/or death with 10 years.Cluster analysis of plasma IL-8, IL-22, TNF-α and GDF-15 identified six distinct patient clusters. Clusters 3 (elevated levels of IL-22, TNF-α, GDF-15), 4 (elevated levels of all four cytokines) and the uncommon Cluster 5 (high GDF-15 only) were associated with worse kidney, cardiovascular and survival outcomes, while Cluster 6 (low cytokine levels) represented patients with slower disease progression and the best long-term outcomes. Over time, patients frequently transitioned to more severe clusters. Conclusion: In CKD G3 patients, systemic inflammation can be stratified using cytokine profiles. Specific cytokine clusters are linked to faster progression of CKD and cardiovascular disease, and to worse long-term outcomes including kidney failure and mortality.
Source: Clinical Kidney Journal
DOI: 10.1093/ckj/sfaf352
Authors: Alberto Martínez-Castelao, Takehiro Hasegawa, Beatriz Fernández-Fernández, José Luis Górriz, Alberto Ortiz, Maria Quero, Gema Fernández-Fresnedo, Jorge-Iván Zamora, Maria Jose Soler, José-Carlos Primo-Alvarez, Nicolas Roberto Robles, Norma Inés Venegas, Felipe Ignacio Ojeda, Antonio Gil-Paraíso, Irene Maria Llorente-Cortijo, Caridad Martínez-Villanueva, Esteban Poch, Jinny Sanchez-Rodriguez, Yun Li, Saruta Yuko, Juan F Navarro-González
Institutions: Bellvitge University Hospital, Sysmex (Germany), Hospital Universitario Fundación Jiménez Díaz, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Universitat de València, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Marqués de Valdecilla University Hospital, Vall d'Hebron Hospital Universitari, Hospital Universitario Infanta Cristina, Hospital Universitario Virgen de la Arrixaca, Hospital Universitario Son Espases, Hospital San Pedro, Complejo Hospitalario Universitario de Ferrol, Hospital General Universitario De Valencia, Hospital Clínic de Barcelona, Hospital Universitario Nuestra Señora de Candelaria
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,335
Funders: Amgen, Eli Lilly and Company, AstraZeneca, Sanofi, Comunidad de Madrid, Fresenius Medical Care North America, European Commission, European Cooperation in Science and Technology, Astellas Pharma, Universidad de Alcalá, Vifor Pharma, Servier, Swedish Orphan Biovitrum, Instituto de Salud Carlos III
Awards: G1259844765, G1301651128, G1318231304, G1362146316, G1518609736, G1584493008, G179174117, Promoviendo las defensas endógenas frente a la enfermedad renal, Body fluid proteome SIGnatures for persoNALised intervention to prevent cardiovascular and renal complications in diabetes, G2089205017, G2256342894, G2525722903, G2650182398, G2854544501, G3030926783, G310854839, Multi-markers risk assessment of kidney sensitivity to injury to personalize prevention of acute kidney injury, G3574591659, Generación y validación de un modelo predictivo para el desarrollo de síndrome cardiorrenal. Integración de la perspectiva de género, el perfil inflamatorio y el sistema FGF23/Klotho., G3661839934, G4022723184, G4290602301, G4352614588, G4469665671, G4480926799, G511460989, G5123827200, G5149128677, G5165426654, G5436261380, G5462010300, G5472687335, G554691909, G5597586574, G5699757257, G5759354985, G5855343624, G6265791144, G6583246094, G6604067511, G6695511762, G7312801975, Conservando la expresión de Klotho para retrasar el envejecimiento renal, Nuevos abordajes diagnósticos y terapéuticos para prevenir la muerte celular e inflamación activados por RIPK1 y RIPK3 en el fracaso renal agudo, ADN LIBRE COMO BIOMARCADOR Y DIANA TERAPEUTICA EN ENFERMEDAD RENAL DIABÉTICA: DIFERENCIAS DE GÉNERO, G7797547491, G7865175063, G8086904238, G8160529855, G8185718001, Developing a framework/model to environmentally sustainable and climate neutral health and care systems using the Kidney care pathway, G8614953158, G8932421531, Spain CKD cause (SPACKDc), G998287453
OpenAlex ID: W4417156286