Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine critically involved in the pathogenesis of multiple forms of nephropathy, including diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), lupus nephritis (LN), acute kidney injury (AKI), and chronic kidney disease (CKD). The objective of this narrative review is to comprehensively analyze the molecular mechanisms by which IL-6 drives renal inflammation and injury, its role across nephropathy subtypes, its value as a biomarker of disease activity, and the therapeutic implications of IL-6 pathway inhibition.  Key findings demonstrate that IL-6 acts via classical and trans-signaling pathways—engaging the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) cascades—to promote glomerular mesangial proliferation, extracellular matrix deposition, podocyte loss, tubular injury, and renal fibrosis. Serum and urinary IL-6 levels correlate with glomerular filtration rate decline, proteinuria, and disease progression across all major nephropathy subtypes. Emerging IL-6 inhibitors, including tocilizumab, satralizumab, and ziltivekimab, show therapeutic promise. In conclusion, IL-6 is both a central pathogenic mediator and a promising therapeutic target in nephropathy, warranting further investigation through prospective clinical trials.

interleukin-6, nephropathy, inflammatory cytokine, JAK/STAT3 signaling, diabetic nephropathy, chronic kidney disease, IL-6 inhibition.

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