Background: Toll-like receptor-4 (TLR4) has been implicated in the pathogenesis of different renal diseases in rodent models. However, in human kidney disease, TLR4 expression and regulation is not well understood. We hypothesized that renal TLR4 expression plays a role in chronic kidney disease (CKD) and is associated with proteinuria, kidney function, histological diagnosis, and inflammatory mediators.
Methods: We quantified TLR4 mRNA as well as expression of macrophage chemoattractant protein-1 (MCP-1), transforming growth factor-β₁ (TGF-β₁) and interleukin-6 (IL-6) in human kidney biopsies from 70 patients with CKD. We measured kidney function, urinary MCP-1 protein excretion, and the amount of chronic damage. Macrophage load was quantified by CD68 and vascularization by CD34 immunostaining.
Results: TLR4 expression correlated significantly with MCP-1 and TGF-β₁ expression. High TLR4 expression was associated with high IL-6 expression. TLR4 expression was significantly upregulated in patients with severe proteinuria, and in patients with chronic ischemic renal damage and IgA nephropathy, when compared to patients with thin glomerular basement membrane disease. TLR4 expression did not correlate with creatinine clearance, renal outcome, macrophage load or chronic damage.
Conclusions: We show for the first time that renal TLR4 expression was significantly associated with the pro-inflammatory marker MCP-1 and the profibrotic molecule TGF-β₁ in kidney biopsies from patients with CKD, suggesting that increased expression of TLR4 is an important feature of CKD.
2011 S. Karger AG, Basel.