Figure 2. Mechanisms that activate toll-like receptors (TLRs) and their impact in cardiorenal syndrome (CRS) type I pathophysiology.

1. Tissue trauma releases products called endogenous ligands that stimulate TLRs. This pathologic trigger is the earliest immune response in AKI injury that sets a cascade of events in motion, which eventually causes massive tissue damage, 2. Amplification of pro-inflammatory cytokines occurs through translocation of transcription factor nuclear factor-kappa B to the nucleus, 3. Sustained TLR activation and inflammatory response leads to apoptosis of renal tubular epithelium, 4. TLRs fuel further cytokine release from neutrophils, monocyte/macrophages, neutrophils, and natural killer cells, resulting in the adaptive immune system activation.