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 under- lying 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 comple- ment-dependent processes. Disorganization of the cytoskeleton with subse- quent redistribution of components of the slit diaphragm and loss of the glomerular charge barrier induces proteinuria in MN. C5b-9 in sublytic quanti- ties stimulates podocytes to produce proteases, oxidants, prostanoids, extra- cellular matrix components, and cytokines. Alterations of the cytoskeleton induced by C5b-9 also lead podocyte depletion through apoptosis and detach- ment of viable podocytes. Furthermore, complement components in proteinuric urine induce proximal tubular epithelial cell injury and mediate progressive tubu- lointerstitial injury in MN.