Cast nephropathy

Schematic diagram illustrating the pathophysiology of AKI in cast nephropathy. Free light chains filtered by the glomerulus are taken up by proximal tubular epithelial cells through the cubilin-megalin receptor complex and clathrin-dependent endocytosis, where they are metabolized in lysosomes. Excess free light chains overwhelm lysosomal capacity, leading to activation of redox pathways, increased NF-kappa-B and mitogen-activated protein kinase expressions, and production of proinflammatory, profibrotic cytokines. Light chains bind to Tamm-Horsfall protein through their variable domain in the lumen of the distal tubule, where they precipitate and form casts.