Figure 1.

Pathophysiological mechanisms involved in renal damage associated with hematuria. Hemoglobin released by intratubular degradation of erythrocytes may be incorporated into proximal tubules through the megalin-cubilin receptor system or degraded in the tubular lumen, releasing heme. Hb, heme and iron accumulation within tubular cells triggers oxidative stress (lipid peroxidation, protein oxidation and aggregation and DNA damage) and inflammatory cytokine secretion (MCP-1 (monocyte chemoattractant protein 1), TNF-alpha (tumor necrosis factor-alpha), and interleukin 6 (IL-6)) throughout NF-κB transcription factor activation. The heme group may be recognized by the Toll-Like Receptor 4 (TLR4), resulting in the activation of the pro-inflammatory downstream signaling pathways like c-Jun kinases, p38, MAPK and NF-κB.