Abstract
KEY POINTS: Higher levels of IL-6, IL-8, monocyte chemoattractant protein-1, TNF-α, and IFN-γ in patients with autosomal dominant polycystic kidney disease highlight inflammation's role in disease progression. Elevated inflammatory markers in autosomal dominant polycystic kidney disease could serve as biomarkers for progression and targets for therapy. BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy that causes adult-onset progressive renal failure. Inflammation and the resulting fibrosis play a crucial role in the pathogenesis. In recent years, an increasing number of inflammatory markers, such as monocyte chemoattractant protein-1 (MCP-1) and TNF-α, that are associated with the development and progression of ADPKD have been identified. The objective of this study was to identify and evaluate potential proinflammatory biomarkers in patients with ADPKD from the German AD(H)PKD registry. METHODS: In this exploratory pilot study, serum concentrations of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IFN-γ, MCP-1, and TNF-α were measured by multiplex immunoassay in 233 adults patients with ADPKD from the German AD(H)PKD registry and compared with an age- and sex-matched healthy control group (n=30). RESULTS: IL-6, IL-8, MCP-1, TNF-α, and IFN-γ concentrations were significantly higher in patients with ADPKD than in healthy controls. In addition, sex influenced the concentrations of MCP-1 and TNF-α in the ADPKD and control groups (MCP-1 male=134.8 pg/L, female=75.11 pg/L; P = 0.0055; TNF-α male=26.22 pg/L, female=21.08 pg/L; P = 0.0038). CONCLUSIONS: Patients with ADPKD have significantly higher levels of IL-6, IL-8, MCP-1, TNF-α, and IFN-γ compared with healthy individuals. These findings underline that inflammation may play a crucial role in the pathogenesis of ADPKD and may be a potential target, both as biomarkers and for therapeutic interventions. CLINICAL TRIAL REGISTRATION NUMBER: NCT02497521.