Membranous nephropathy (MN) is a kidney disease that targets the glomeruli, the tiny filtering units within the kidneys. It is a leading cause of nephrotic syndrome in adults. MN involves an immune-mediated process that disrupts the kidney’s ability to retain essential proteins, leading to symptoms and potential long-term complications. Understanding the mechanism of damage, causes, and treatments is important for those affected by this diagnosis.
How Membranous Nephropathy Damages the Kidney
The glomeruli filter waste and fluid while blocking large molecules, such as protein, from escaping the bloodstream. In membranous nephropathy, this delicate filtering barrier is compromised by the accumulation of immune deposits. These deposits form on the outside of the glomerular basement membrane.
The buildup of these immune complexes causes inflammation and thickening of the membrane. Specialized cells called podocytes, which help form the final filtration slits, become damaged by this process. Damage to the podocytes and membrane thickening destroy the barrier’s integrity, causing it to become “leaky.” This defect allows significant amounts of protein, primarily albumin, to spill into the urine, resulting in proteinuria.
Understanding the Causes: Primary vs. Secondary MN
Membranous nephropathy is categorized as Primary or Secondary based on its origin. The majority (75% to 80%) are classified as Primary MN, meaning the cause originates within the kidney and is not linked to another systemic disease. Primary MN is considered an autoimmune disorder where the body mistakenly produces antibodies that attack the kidney’s own cells.
The most common target in Primary MN is the Phospholipase A2 Receptor (PLA2R) protein found on the surface of the podocytes. Autoantibodies against PLA2R are present in most adults with the primary form, and their binding triggers the formation of damaging immune deposits.
The remaining cases are classified as Secondary MN, where the kidney damage is a consequence of another health issue. Common secondary causes include autoimmune diseases (such as Lupus), chronic infections (like Hepatitis B or C), certain cancers (lung or colon), and exposure to specific medications or heavy metals. Identifying the correct category is important because treatment for Secondary MN often focuses on resolving the underlying disease.
Recognizing the Common Symptoms
The massive loss of protein results in several noticeable physical changes. The most common symptom is edema (swelling), which occurs because low protein levels allow fluid to leak out of blood vessels and accumulate in tissues.
This swelling is often first observed in the legs, ankles, and feet, but it can also appear around the eyes. Patients may also notice foamy or frothy urine, a direct result of the high concentration of protein being excreted. Other symptoms include fatigue, weight gain from fluid retention, and poor appetite. MN can also lead to hyperlipidemia (high fat levels in the blood) and an increased risk of blood clots.
The Diagnostic Process
Diagnosing membranous nephropathy begins with initial screening tests to assess kidney function and detect protein loss. A urinalysis measures protein in the urine; heavy proteinuria (more than 3.5 grams per day) indicates nephrotic syndrome. Blood tests check creatinine and blood urea nitrogen (BUN) to estimate the kidney’s filtration rate, and measure albumin, the main protein lost.
Traditionally, a kidney biopsy has been the gold standard for definitive diagnosis and ruling out other causes of nephrotic syndrome. This procedure involves taking a small tissue sample to be examined under a microscope, allowing doctors to visualize the characteristic immune deposits. However, recent advances have made non-invasive blood tests for the anti-PLA2R antibody highly valuable for diagnosing Primary MN. A positive anti-PLA2R test in a patient with nephrotic syndrome may be sufficient to confirm the diagnosis, potentially avoiding a biopsy.
Treatment Approaches and Long-Term Outlook
Treatment for membranous nephropathy involves supportive care and disease-specific therapy, tailored to the patient’s risk of progression.
Supportive Care
Supportive measures aim to control symptoms and slow the rate of kidney damage. This includes using Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin II Receptor Blockers (ARBs), which manage blood pressure and reduce protein loss in the urine.
Diuretics are often prescribed to reduce edema by encouraging the body to excrete excess fluid and sodium. Managing high cholesterol with statin medications is also important, as hyperlipidemia is a common complication. Patients are advised to follow a low-sodium diet to help control fluid retention and manage blood pressure.
Disease-Specific Therapy
This therapy is reserved for patients at high risk of progressive kidney failure and focuses on suppressing the autoimmune response. Immunosuppressive drugs target the cells that produce the damaging autoantibodies. The anti-CD20 monoclonal antibody Rituximab has emerged as a first-line agent, working by depleting B-cells responsible for producing anti-PLA2R antibodies.
Other options include alkylating agents like cyclophosphamide (often combined with corticosteroids) or calcineurin inhibitors such as tacrolimus. The choice of agent depends on the disease’s severity and the patient’s risk factors. The goal is to achieve remission, marked by a significant reduction in proteinuria, thereby protecting the kidneys from long-term damage.
Long-Term Outlook
The long-term outlook for MN is variable, often described by the “rule of thirds.” One-third of patients may experience spontaneous remission without needing immunosuppressive treatment. Another third will have a stable course with persistent proteinuria but maintained kidney function. The final third may see their disease progress to end-stage kidney disease (ESKD) within 10 years, requiring dialysis or a kidney transplant. Regular monitoring of proteinuria and kidney function is essential to guide treatment decisions and predict the eventual outcome.