Association of peripheral TLR9 gene expression with renal function and inflammatory cytokine profile in chronic kidney disease: A case-control study

BACKGROUND: Chronic kidney disease (CKD) involves persistent low-grade inflammation that perpetuates kidney injury. Toll-like receptor 9 (TLR9), an innate-immune sensor of unmethylated CpG and mitochondrial DNA, may contribute to this process, but its peripheral-blood expression in CKD remains unclear. METHODS: In a cross-sectional case-control study, whole-blood TLR9 mRNA (2-ΔΔCt method) was compared between 60 CKD patients (KDIGO stages 1-5) and 60 matched, comorbidity-free controls. Serum TNF-α and IL-41 were measured by ELISA. Associations with renal function were assessed by correlation, regression, and ROC analysis. RESULTS: TLR9 fold-change was markedly higher in CKD patients than controls (median 2.37 vs. 0.98; P < 0.001) and rose progressively with CKD stage (ρ = 0.94). TLR9 correlated strongly with eGFR (ρ = -0.91) and remained independently associated with CKD status after adjustment (adjusted odds ratio 66.6, P < 0.001). TNF-α and IL-41 were also elevated and correlated with TLR9. TLR9 discriminated CKD from controls with AUC 0.894, rising to 0.976 combined with TNF-α and IL-41 (cross-validated 0.970). CONCLUSIONS: Peripheral TLR9 expression is substantially elevated in CKD, tracks disease severity and renal dysfunction, and remains statistically significant after adjustment for demographic and clinical confounders, supporting its potential as a peripheral blood biomarker of CKD-related inflammation.