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Uptodate Reference Title
Cast nephropathy
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.