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.