Membranous Nephropathy

Membranous nephropathy is an immune-mediated glomerular disease. In primary disease, autoantibodies most often target the phospholipase A2 receptor (PLA2R) on podocytes; anti-THSD7A antibodies are less common. The antibodies create immune complexes along the subepithelial side of the glomerular basement membrane. Complement activation, including formation of the membrane attack complex, injures podocytes without the marked inflammatory cellular response seen in some nephritic diseases. The injured podocytes lose their normal foot-process architecture, or develop foot-process effacement. The filtration barrier then becomes excessively permeable to albumin and other plasma proteins. This explains the characteristic nephrotic pattern: heavy proteinuria, falling serum albumin, oedema, and hyperlipidaemia. The liver increases lipoprotein production in response to the altered plasma protein balance, contributing to the lipid elevation. Protein loss also changes priorities beyond fluid balance. Urinary loss of antithrombin and other anticoagulant proteins, together with increased platelet and coagulation activity, creates a hypercoagulable state. A patient can therefore have substantial thromboembolic risk even when the serum creatinine is initially normal. Preserved creatinine does not make severe protein loss benign. Membranous nephropathy may be primary or secondary. Secondary disease...