Membranous nephropathy, also called membranous glomerulonephritis, is a rare kidney condition where the body’s immune system mistakenly attacks the tiny filters in the kidneys. This leads to protein leaking into the urine and can cause swelling throughout the body. Understanding this condition is important because early detection and proper management can help protect kidney function and prevent serious complications.
Understanding Membranous Nephropathy
Your kidneys contain thousands of microscopic filtering units called glomeruli. These tiny structures work constantly to clean waste products from your blood while keeping important proteins and nutrients inside your body. In membranous nephropathy, the immune system produces antibodies that attack these delicate filters, causing them to become inflamed and damaged. When this happens, the kidneys lose their ability to properly filter blood, allowing proteins to escape into the urine.[1]
The condition can develop suddenly or progress slowly over many years. It is not uncommon for people to have membranous nephropathy for several years without knowing it, as symptoms may be mild or absent in the early stages. The disease can affect kidney function in different ways for different people. Some individuals may experience a complete recovery, others may live with stable but reduced kidney function, while some may progress toward more serious kidney problems.[1]
How Common Is This Condition
Membranous nephropathy is a rare disease. Only about 1 in every 5,000 people develops this condition. It is the second most common type of kidney disease that causes nephrotic syndrome in adults, which is a group of symptoms including protein in the urine, swelling, and low blood protein levels.[1][2]
The condition affects men more often than women and is most commonly diagnosed in people between the ages of 30 and 60, particularly men aged 50 to 60. It is more frequently seen in people of European, Middle Eastern, or North African ancestry. Children rarely develop membranous nephropathy, making it primarily an adult disease.[1][3]
Among adults with nephrotic syndrome, membranous nephropathy is one of the most common causes. However, focal segmental glomerulosclerosis has recently become the leading cause, making membranous nephropathy the second most frequent diagnosis in this category.[2][3]
What Causes Membranous Nephropathy
Membranous nephropathy is divided into two main types based on what triggers the immune system attack: primary and secondary. Understanding which type you have is important because it affects treatment decisions and outcomes.[1]
Primary membranous nephropathy accounts for about 75 to 80 percent of all cases. In this type, the condition directly affects the kidneys without being caused by another disease. It is considered an autoimmune disease, meaning the body’s defense system mistakenly identifies healthy kidney tissue as foreign and attacks it. The most common trigger is the production of antibodies against a protein called phospholipase A2 receptor, or PLA2R, which is found on the surface of kidney cells. These anti-PLA2R antibodies are present in 70 to 80 percent of people with primary membranous nephropathy.[2][4]
Other antibodies have been identified as well. About 15 to 20 percent of cases involve antibodies against neural epidermal growth factor-like 1, known as NELL-1. A smaller percentage, between 1 and 5 percent, involves antibodies against thrombospondin type 1 domain-containing 7A, abbreviated as THSD7A. Other rare antibodies have also been discovered, including those targeting neutral endopeptidase and exostosin.[2][4]
Secondary membranous nephropathy makes up about 20 to 25 percent of cases. This type occurs when another health condition or exposure damages the kidneys and leads to the development of membranous nephropathy. Many different conditions can trigger secondary membranous nephropathy. Infections are one common cause, including hepatitis B, hepatitis C, syphilis, malaria, HIV, and schistosomiasis.[2][5]
Cancer is another important cause of secondary membranous nephropathy. Various types of cancer can trigger the condition, particularly adenocarcinoma and squamous cell carcinoma of the lungs and gastrointestinal tract. Blood cancers, also called hematological malignancies, can also lead to membranous nephropathy. Certain medications have been linked to the disease, including nonsteroidal anti-inflammatory drugs (NSAIDs), drugs that block tumor necrosis factor-alpha, penicillamine, and probenecid.[2][5]
Exposure to heavy metals, particularly gold and mercury, can damage the kidneys and cause membranous nephropathy. Autoimmune diseases, where the immune system attacks various parts of the body, are also associated with secondary membranous nephropathy. These include systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, and IgG4-related nephropathy. Other causes include hematopoietic stem cell transplant, graft versus host disease, and diabetes mellitus.[2][5]
Who Is at Higher Risk
Several factors can increase your likelihood of developing membranous nephropathy. Being male puts you at higher risk, as men develop the condition more frequently than women. Age is another important risk factor, with people over 40 years old being more susceptible to the disease.[12]
Certain genetic factors may increase risk. People with a specific genetic marker called HLA-DR3 appear to be more prone to developing membranous nephropathy. If you have an autoimmune disease, your risk is elevated because these conditions can trigger secondary membranous nephropathy. The same is true for chronic infections with hepatitis B or C, as well as syphilis.[12]
Having certain types of cancer, particularly solid organ cancers, increases your risk of developing secondary membranous nephropathy. Taking certain medications regularly, especially NSAIDs or other drugs known to affect the kidneys, can also raise your risk. Other conditions that increase susceptibility include sarcoidosis and having received an organ transplant in the past.[12]
Recognizing the Symptoms
The symptoms of membranous nephropathy primarily result from the loss of protein in the urine and the body’s inability to maintain proper fluid balance. Many people with the condition experience edema, which is swelling caused by fluid buildup in body tissues. This swelling typically appears in the ankles, feet, and face, and can be quite noticeable. The swelling occurs because proteins that normally keep fluid in the blood vessels are being lost in the urine, allowing fluid to leak into surrounding tissues.[1][5]
Proteinuria, or protein in the urine, is a hallmark of membranous nephropathy. While you cannot feel protein in your urine, you may notice that your urine appears foamy or frothy, similar to beer foam. This happens because proteins create bubbles when they mix with water in the toilet bowl. The amount of protein lost can be substantial, often exceeding 3.5 grams per day.[1][2]
Fatigue and weakness are common symptoms that can significantly affect daily life. These occur partly because of protein loss and partly because the kidneys are not functioning optimally. Weight gain is another frequent symptom, but this is usually water weight from fluid retention rather than fat. You may also notice changes in how often you urinate, either more or less than usual.[1][7]
Some people develop high blood pressure as a result of kidney damage. High cholesterol is also common in membranous nephropathy because the liver tries to compensate for lost proteins by making more, which includes producing extra cholesterol. Poor appetite can develop as kidney function declines. In some cases, you might notice blood in your urine, which may appear pink, red, or brown. Shortness of breath or trouble breathing can occur if fluid builds up in the lungs.[1][5]
It is important to know that many people with membranous nephropathy do not experience noticeable symptoms, especially in the early stages. The condition may only be discovered during routine blood or urine tests performed for other reasons. This is why regular check-ups are important, particularly if you have risk factors for kidney disease.[1][7]
Preventing Membranous Nephropathy
Because primary membranous nephropathy is an autoimmune condition with no clearly understood cause, there is no proven way to prevent it from developing. However, you can take steps to reduce your risk of secondary membranous nephropathy and protect your overall kidney health.[1]
Protecting yourself from infections that can damage the kidneys is important. Getting vaccinated against hepatitis B can help prevent one of the infections associated with secondary membranous nephropathy. Practicing safe behaviors to avoid sexually transmitted infections, including HIV and syphilis, also reduces your risk. If you travel to areas where malaria is common, taking appropriate preventive medications is wise.[2]
Using medications carefully can help protect your kidneys. Avoid taking NSAIDs regularly without medical supervision, as these drugs can harm the kidneys over time. If you need pain relief, talk to your doctor about the safest options for your situation. Never take medications prescribed for someone else, and always inform your healthcare providers about all medications and supplements you are taking.[2]
Avoiding exposure to toxic substances, particularly heavy metals like mercury and gold, is important for kidney health. If your work involves handling these substances, make sure you follow all safety protocols and use appropriate protective equipment. Limiting exposure to other environmental toxins whenever possible is also beneficial.[2]
Managing underlying health conditions can help prevent secondary membranous nephropathy. If you have an autoimmune disease like lupus or rheumatoid arthritis, working closely with your doctor to keep the condition under control may reduce your risk of kidney complications. Regular cancer screenings appropriate for your age and risk factors can help detect cancers early, potentially before they affect the kidneys.[2]
Maintaining overall kidney health through lifestyle choices is always beneficial. Staying well-hydrated by drinking adequate amounts of water supports kidney function. Eating a balanced diet with moderate amounts of protein and limiting salt intake can help your kidneys work efficiently. Controlling blood pressure and blood sugar if you have diabetes protects your kidneys from damage. Not smoking and limiting alcohol consumption are also important for kidney health.[5]
How the Disease Affects Your Body
Understanding what happens inside your body when you have membranous nephropathy helps explain why symptoms develop and why treatment is necessary. The disease process begins at the microscopic level, in the tiny filtering units of your kidneys called glomeruli. Each glomerulus contains a specialized membrane called the glomerular basement membrane, which acts as a barrier to keep important substances in your blood while allowing waste products to pass through into the urine.[4]
In membranous nephropathy, antibodies and other immune proteins form complexes that deposit along this basement membrane. These deposits cause the membrane to thicken and become damaged. The deposits typically form on the outer side of the membrane, in an area called the subepithelial region. As more immune complexes accumulate, they create small bumps or spikes on the membrane surface that can be seen under a microscope.[4]
The immune deposits trigger inflammation in the glomeruli, which further damages the filtering membrane. Cells in the kidney called podocytes, which normally help maintain the filtering barrier, become injured. These podocyte cells have foot-like projections that wrap around the blood vessels in the glomerulus, forming a crucial part of the filter. When they are damaged, gaps open up in the filtering barrier.[2]
The damaged barrier loses its ability to prevent proteins from passing through. Normally, the glomerular basement membrane has a negative electrical charge that repels proteins, which also carry a negative charge. This charge barrier is lost in membranous nephropathy, allowing proteins, especially albumin, to leak into the urine. This process is called albuminuria, and it is the main reason for the nephrotic syndrome symptoms.[2]
As protein leaks out of the bloodstream, the concentration of protein in your blood drops, leading to hypoalbuminemia, or low blood albumin levels. Albumin is important for keeping fluid inside blood vessels. When albumin levels fall, fluid escapes from the vessels and accumulates in body tissues, causing the swelling that characterizes the condition.[2]
Your liver responds to the low protein levels by trying to make more protein. However, in the process, it also produces extra cholesterol and other fats, leading to high cholesterol and dyslipidemia. The kidneys may also become less efficient at removing waste products from the blood, which can cause creatinine and other waste substances to build up. If kidney function declines significantly, it can progress to acute kidney injury or chronic kidney disease.[2]
The loss of proteins that help with blood clotting regulation puts you at increased risk for dangerous blood clots. The combination of protein loss, abnormal blood clotting factors, and sometimes immobility from swelling can lead to deep vein thrombosis (blood clots in the legs) or pulmonary embolism (blood clots that travel to the lungs). These complications can be life-threatening if not recognized and treated promptly.[1]
