Membranous nephropathy is the most common cause of primary nephrotic syndrome in adults, most often presenting in the fifth and sixth decades. It is an immune-mediated disease characterized by immune complex deposition in the subepithelial portion of glomerular capillary walls. The antigen in the primary form of the disease appears to be a phospholipase A2 receptor (PLA2R) on the podocyte in 70–80% of patients. Secondary disease is associated with infections, such as hepatitis B and C, endocarditis, and syphilis; underlying carcinomas (some of these cases may involve autoimmunity to podocyte-expressed thrombospondin type-1 domain-containing 7A [THSD7A]); autoimmune disease, such as SLE, mixed connective tissue disease, and thyroiditis; and certain drugs, such as NSAIDs and captopril. The course of disease is variable, with about 50% of patients progressing to ESRD over 3–10 years. Poorer outcome is associated with concomitant tubulointerstitial fibrosis, male sex, elevated serum creatinine, hypertension, and proteinuria greater than 10 g/day.
Patients with membranous nephropathy and nephrotic syndrome have a higher risk of hypercoagulable state than those with nephrosis from other etiologies; there is a particular predisposition to renal vein thrombosis in these patients.