Mediators of renal injury in membranous nephropathy

Membranous nephropathy (MN) is a common glomerular disease characterized by podocyte injury and proteinuria, often in the nephrotic range. Heymann nephritis (HN), a rat model of MN, has contributed to elucidation of the underlying pathogenic mechanisms which involve in situ formation of subepithelial immune deposits of antibody reactive with podocyte antigen(s) that produce glomerular injury by damaging and/or activating podocytes through complement-dependent processes. Disorganization of the cytoskeleton with subsequent redistribution of components of the slit diaphragm and loss of the glomerular charge barrier induces proteinuria in MN. C5b-9 in sublytic quantities stimulates podocytes to produce proteases, oxidants, prostanoids, extracellular matrix components, and cytokines. Alterations of the cytoskeleton induced by C5b-9 also lead podocyte depletion through apoptosis and detachment of viable podocytes. Furthermore, complement components in proteinuric urine induce proximal tubular epithelial cell injury and mediate progressive tubulointerstitial injury in MN.