Primary membranous nephropathy is a kidney disease impacting the tiny filtering units within the kidneys called glomeruli. It is an autoimmune disorder where the body’s immune system mistakenly targets and damages its own healthy kidney cells. This damage affects the kidney’s ability to properly filter waste products from the blood, resulting in proteins leaking into the urine.
What Primary Membranous Nephropathy Is
Primary membranous nephropathy is an autoimmune condition where the body’s immune system produces autoantibodies that mistakenly attack components of the kidney’s filtering units, the glomeruli. These glomeruli contain specialized cells called podocytes. The immune system targets proteins on the surface of these podocytes, particularly the phospholipase A2 receptor (PLA2R) and, less commonly, thrombospondin type-1 domain-containing protein 7A (THSD7A).
The binding of these autoantibodies to the podocytes leads to the formation of immune complex deposits beneath the epithelial cells of the glomeruli. These deposits cause the glomerular capillary walls to thicken, impairing the normal permeability of the glomerular basement membrane. This structural change compromises the kidney’s filtration barrier, allowing large amounts of protein to leak into the urine.
The discovery of anti-PLA2R antibodies in 2009 was a significant advancement. These antibodies are found in 70% to 80% of patients with primary membranous nephropathy. They are highly specific for the condition and their levels can correlate with disease severity. In a smaller percentage of cases, around 3% to 5%, antibodies against THSD7A are identified.
Identifying Primary Membranous Nephropathy
Primary membranous nephropathy often presents with symptoms of nephrotic syndrome. A common sign is proteinuria, an excessive amount of protein in the urine, which may appear foamy. Fluid retention, or edema, is also frequently observed, causing swelling, particularly in the legs, ankles, and around the eyes. Other general symptoms can include fatigue, weight gain from fluid retention, and sometimes high blood pressure.
The diagnostic process typically begins with urine tests to detect proteinuria and assess its severity. Blood tests check overall kidney function by measuring levels of substances like blood urea nitrogen (BUN) and creatinine, and evaluate protein levels in the blood. These blood tests also look for specific antibodies, notably anti-PLA2R antibodies, which can strongly indicate primary membranous nephropathy.
While blood tests for anti-PLA2R antibodies are highly specific and can suggest the diagnosis, a kidney biopsy remains the definitive method for confirming primary membranous nephropathy. This procedure involves taking a small tissue sample from the kidney. The biopsy reveals characteristic thickening of the glomerular capillary walls and the presence of immune deposits, confirming the diagnosis and ruling out other kidney conditions.
Treatment and Long-Term Management
Management of primary membranous nephropathy involves a combination of supportive care and immunosuppressive therapies. Supportive care aims to manage symptoms and protect kidney function. This includes medications to control blood pressure, such as ACE inhibitors or ARBs, which can also help reduce protein leakage into the urine. Diuretics may be prescribed to alleviate swelling caused by fluid retention, and dietary modifications, like reducing sodium intake, can help manage fluid balance.
Immunosuppressive therapies are considered for patients with persistent high levels of protein in the urine despite supportive care, or for those at high risk of disease progression. These medications work by dampening the immune system. Commonly used agents include corticosteroids, which reduce inflammation, and cyclophosphamide. Calcineurin inhibitors like tacrolimus and cyclosporine are also used to suppress the immune response, often inducing remission.
Rituximab, a biologic medication, targets B cells. It has become a significant treatment option for primary membranous nephropathy, particularly for those with moderate to high risk of progression. The goal of these treatments is to achieve remission, meaning a reduction in proteinuria and stabilization or improvement of kidney function. Monitoring anti-PLA2R antibody levels can guide treatment decisions, as a decrease in these levels often predicts clinical remission.
The long-term outlook for primary membranous nephropathy is variable. Approximately one-third of patients experience spontaneous remission without specific immunosuppressive therapy, particularly those with low anti-PLA2R antibody levels. However, another one-third may see their disease progress to end-stage kidney disease (ESKD) within 10 years if left untreated. Achieving remission significantly improves kidney survival and reduces the risk of ESKD.
Ongoing monitoring of proteinuria, kidney function, and antibody levels is important. While immunosuppressive therapies can reduce the risk of ESKD, they also carry potential side effects. Relapses can occur even after initial remission, making continued medical follow-up necessary. For those who progress to ESKD, kidney replacement therapies such as dialysis or kidney transplant become necessary.