Definition of Membranous nephropathy

Membranous nephropathy: A frequent type of primary glomerular disease -- a disease affecting the glomerulus, the tiny ball-shaped structure in the kidney composed of capillary blood vessels that is actively involved in the filtration of the blood to form urine. The main sign of the disease is marked proteinuria (protein in the urine).

The majority (about 2/3) of cases are primary (or idiopathic), meaning the cause is not known. The remaining cases are secondary to conditions such as cancer, infection, and drug side effects. Idiopathic MN is the most common cause of primary nephrotic syndrome in older (>60 years) Caucasian adults and is rare in children. It usually accounts for less than 5% of pediatric patient undergoing biopsy for nephrotic syndrome. About 30% of all biopsy specimens for primary nephrotic syndrome reveal membranous nephropathy in adults and about 50% in older Caucasian adults. A large number of agents appear to be capable of initiating membranous nephropathy in genetically susceptible individuals. More common agents include infections such as hepatitis B (less commonly hepatitis C and syphilis), immune diseases such as lupus and diabetes mellitus (less commonly associated with rheumatoid arthritis and other connective tissue diseases), medications such as gold, penicillamine, non-steroidal anti-inflammatory agents, and captopril, and some tumors (the colon, kidney, and lung are the most common primary sites). Membranous nephropathy has been associated with the chronic immune response to renal transplants as well. Without intervention, about 40% of people with membranous nephropathy progress to end-stage renal failure after 10 years. Conversely, up to 30% of people with have a spontaneous remission and approximately 30% of people will have stable renal function. Female sex and lower grade (non-nephrotic) proteinuria at presentation are the only two features associated with a higher likelihood of spontaneous remission. Although the majority of membranous nephropathy patients do reasonably well long term, membranous nephropathy is still the second or third leading cause of end-stage renal failure among subjects with primary glomerulonephritis. Factors associated with worse renal survival in membranous nephropathy include older age at presentation, male sex, hypertension, decreased renal function (elevated creatinine and/or decreased GFR) at time of presentation, higher level of proteinuria, and evidence of chronic features (scarring) on biopsy. Relapses after complete remission have occurred in approximately 25% to 40% of patients. Relapses have been reported up to 20 years after the primary remission. the great majority of patients will relapse only with low-range proteinuria and will maintain stable long-term kidney function with conservative management alone. In contrast, the relapse rate is as high as 50% in those achieving only a partial remission. Achievement of either a complete or partial remission, however, significantly slows progression and increases renal survival.

Membranous nephropathy is a glomerular immune-complex disease. Immune deposits form in the glomerular basement membrane that cause a membrane-like thickening. The constituent immune complexes consist of IgG. Cells called podocytes and their membrane-associated proteins play a pivotal role in the development of the disease by providing antigenic targets for circulating antibodies to form the glomerular immune deposits. Membranous nephropathy is also called membranous glomerulonephritis.

The disease can occur before birth due to transmission of antibodies from the mother to the baby. The antibodies are directed against an antigen in podocytes called neutral endopeptidase (NEP). Mutations that truncate (shorten) the metallomembrane endopeptidase (MME) gene, which encodes NEP, have been found to cause the neonatal form of this disease.

Treatment involves the use of non-immunosuppressive therapy in all patients. In patients who do not respond adequately to non-immunosuppressive therapy or those patients who have a higher risk of progression to end-stage renal failure are generally offered immunosuppressive therapy as well. Several immunosuppressive regimens have been shown to be successful. Agents that have been utilized include corticosteroids (e.g. prednisone), cytotoxic agents, calcineurin inhibitors, mycophenolate, rituximab, eculizumab, and ACTH. These agents modify the immune response and help decrease the formation of immune deposits in the glomerular basement membrane. Non-immunosuppressive therapy is directed at control of edema, hypertension, hyperlipidemia, and proteinuria; it is similar to that used for nephrotic syndrome of any cause. Blood pressure control is important for both renal and cardiovascular protection. For patient with proteinuria of more than 1 gram per day, the target for blood pressure is 125/75 mm Hg. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are cardioprotective and can reduce proteinuria and slow progression of renal disease. Patients with significant proteinuria almost always have elevated serum cholesterol and triglyceride levels. Although not proven, it is recommended to use statin agents to reduce cholesterol levels.


Last Editorial Review: 9/20/2012

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