Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (i.e., those of European, Middle Eastern, or North African ancestry.). It is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) recently becoming the most common. Signs and symptoms Most people will present as nephrotic syndrome, with the triad of albuminuria, edema and low serum albumin (with or without kidney failure). High blood pressure and high cholesterol are often also present. Others may not have symptoms and may be picked up on screening, with urinalysis finding high amounts of protein loss in the urine. A definitive diagnosis of membranous nephropathy requires a kidney biopsy, though given the very high specificity of anti-PLA2R antibody positivity this can sometimes be avoided in patients with nephrotic syndrome and preserved kidney function Causes Traditional definitions split membranous nephropathy into 'primary/idiopathic' or 'secondary'. It is likely that instead the field will move to novel classification on the basis of the specific autoantigen detected, though given the current lack of clinical assays (other than for PLA2R autoantibodies) this may be several years off still. Primary/idiopathic Traditionally 85% of MGN cases are classified as primary membranous glomerulonephritis—that is to say, the cause of the disease is idiopathic (of unknown origin or cause). This can also be referred to as idiopathic membranous nephropathy. Antibodies to an M-type phospholipase A2 receptor are responsible around 60% of cases of membranous nephropathy. Testing for these anti-PLA2R has revolutionised diagnosis and treatment of this disease in antibody positive patients, and tracking titre level over time allows you to predict risk of disease progression and chance of spontaneous remission There is little secondary disease association with PLA2R autoantibodies. In 2014, a second autoantigen was discovered, the thrombospondin type 1 domain-containing 7A (THSD7A) system that might account for an additional 1% of membranous nephropathy cases, and appears to be associated with malignancies. Further studies have identidied more novel auto-antigens responsible for causing a membranous nephropathy pattern of injury continue to be published, with antibodies discovered against: NELL-1 likely the second most common autoantibody with prevalence in MN of 5-10%. It has a heterogenous pattern of secondary association, from none to sarcoidosis, malignancy, drugs and infections. Like PLA2R, antibody titres go into remission with treatment. EXT1/EXT2 was reported in 2019. It is predominantly found in