Abstract
Background: Chronic Kidney Disease (CKD) progression is driven by intertwined pathways of inflammation, fibrosis, and disordered mineral metabolism. While cytokines like IL-6 and TNF-α are established inflammatory markers, their prognostic value may be enhanced by combining them with emerging partners like Galectin-3 (Gal-3, fibrosis/pro-inflammatory amplifier) and Fibroblast Growth Factor-23 (FGF-23, mineral bone disorder). We investigated the individual and combined prognostic power of this novel panel for renal and cardiovascular (CV) outcomes.
Methods: In this prospective, single-center cohort study, 218 patients with CKD stages 3-4 were enrolled. Baseline serum levels of IL-6, IL-1β, TNF-α, TGF-β, Gal-3, and FGF-23 were measured. Patients were followed for 36 months for a primary composite endpoint: ≥40% decline in eGFR, progression to kidney failure requiring replacement therapy (KFRT), or a major adverse CV event (MACE). Cox proportional-hazards models, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curves were employed.
Results: Over 36 months, 68 patients (31.2%) reached the composite endpoint. Elevated levels of all biomarkers, except IL-1β, were individually associated with the endpoint in univariate analysis. In multivariate Cox regression, only IL-6 (HR: 1.82, 95% CI: 1.30-2.55), Gal-3 (HR: 2.15, 95% CI: 1.45-3.18), and FGF-23 (HR: 1.95, 95% CI: 1.35-2.82) remained independent predictors after adjustment for age, diabetes, eGFR, and albuminuria. A "Triple-Biomarker Risk Score" (TBRS), combining tertiles of IL-6, Gal-3, and FGF-23, showed a powerful graded association with risk. Patients in the high-TBRS group had a 9-fold higher risk (HR: 9.10, 95% CI: 3.82-21.68) compared to the low-score group. The area under the ROC curve (AUC) for the TBRS (0.84) was significantly superior to that of eGFR alone (0.72, p<0.01).
Conclusion: The combination of a classic inflammatory cytokine (IL-6), a fibrotic/pro-inflammatory lectin (Gal-3), and a phosphaturic hormone (FGF-23) provides a superior prognostic signature in moderate CKD. This panel reflects key pathological axes—inflammation, fibrosis, and mineral dysregulation—and significantly improves risk stratification for both renal and cardiovascular outcomes.
Keywords
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.