Although the majority of membranous nephropathy falls under the “idiopathic” category, there are a variety of causes of secondary membranous nephropathy. It is quite important to eliminate these entities as possible diagnoses, as the treatment for secondary membranous nephropathy relies primarily on treatment of the underlying cause of disease whereas idiopathic membranous nephropathy often involves the use of steroids and/or cytotoxic agents.
Broadly speaking, the secondary causes of membranous nephropathy can be broken down into 4 general categories:
1. Infection-associated Membranous Nephropathy: hepatitis B and hepatitis C are both associated with membranous nephropathy. Because diseases such as malaria, schistosomiasis, TB, and leprosy are likewise associated with membranous nephropathy, secondary nephrotic syndrome is likely much more common in developing countries subject to these tropical diseases. Syphilis is also on the list.
2. Disease-associated Membranous Nephropathy: it is well-known that MN may be see in lupus (“WHO Type V Lupus Nephritis”) either alone or in combination with other lupus-related pathologies. A variety of the other conditions associated with MN are also autoimmune diseases (e.g., rheumatoid arthritis, Sjogren’s syndrome). Diabetes mellitus and membranous nephropathy have also been linked, as has sickle cell disease.
3. Drug-induced Membranous Nephropathy: the classic offenders are gold, penicillamine, NSAIDs, and captopril, though there are case reports for many others.
4. Malignancy-associated Membranous Nephropathy: although there appears to be a increased relative risk of solid tumors and lymphomas in patients with membranous nephropathy as compared to the general population, this association is still somewhat poorly defined and remains controversial. Many would simply recommend age-appropriate cancer screening (e.g., mammogram, screening colonoscopy, etc) in the patient with newly-diagnosed nephrotic syndrome without any other evidence for malignancy rather than a large-scale imaging workup.
Not surprisingly the acronym for disease-associated MN is DAMN!