Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms

Membranous nephropathy is a frequent cause of nephrotic syndrome in adults. In most patients, it appears as a primary renal disease but in about 20 % of cases membranous nephropathy is associated with systemic conditions such as systemic lupus erythematosus, infections or cancer, or with drug exposure. Reliable differentiation between primary and secondary membranous nephropathy has important implications for the patient, because of different therapeutic approaches between the different forms. The recent in vivo definition of glomerular targets of autoimmunity in idiopathic membranous nephropathy represented a real breakthrough and nowadays more than one podocyte antigen is considered in some way implicated in the pathogenesis of human membranous nephropathy. Specific antibodies against all these components have been detected in serum of patients and could become biomarkers of membranous nephropathy and/or of disease activity. In this brief review, we discuss the usefulness of newly described autoantibodies in the differential diagnosis of secondary membranous nephropathy. Histological clues for recognizing the two pathological entities are also analysed with regard to the available scientific evidence on this issue. Our evaluation shows that more research is needed to identify the best approach to reach a correct diagnosis of primary or secondary membranous nephropathy.