Membranous Nephropathy

Membranous nephropathy is a kidney disease that harms the tiny filters in the kidneys called glomeruli. It damages the glomerular basement membrane. This leads to losing protein in the urine, known as proteinuria.

People with this condition often get nephrotic syndrome. This is marked by severe protein loss, swelling, and high cholesterol levels.

Membranous nephropathy can seriously affect kidney function over time. It’s important for patients and healthcare professionals to know about its causes, symptoms, and treatments. Understanding membranous nephropathy helps individuals work with their healthcare team to manage the condition well.

What is Membranous Nephropathy?

Membranous nephropathy is a kidney disorder that makes the glomerular basement membrane thick. This leads to proteinuria and impaired kidney function. The glomeruli, tiny filtering units in the kidneys, are affected. They are responsible for removing waste and excess fluid from the blood while keeping essential proteins.

There are two main types of membranous nephropathy: primary (idiopathic) and secondary. Idiopathic membranous nephropathy is the most common, making up about 75% of cases. It has no known cause. Secondary membranous nephropathy is linked to infections, malignancies, and autoimmune disorders.

Prevalence and Risk Factors

Membranous nephropathy is rare, affecting about 1-2 people per 100,000 each year. It mainly strikes adults aged 30 to 50, with men more likely to be affected than women. Several factors can increase the risk of developing this condition:

Knowing the risk factors for membranous nephropathy helps doctors spot those at higher risk. This allows for early screening and management.

Causes of Membranous Nephropathy

Membranous nephropathy can be divided into two main types: primary (idiopathic) and secondary. Knowing the difference is key for the right diagnosis and treatment.

Primary (Idiopathic) Membranous Nephropathy

Primary membranous nephropathy, or idiopathic membranous nephropathy, makes up about 80% of cases. It’s thought to be an autoimmune disorder. This means the body’s immune system attacks the glomeruli, damaging the filtration membranes.

The exact reason for this autoimmune attack is not yet known. But, research has found specific antibodies in many patients. These include anti-PLA2R and anti-THSD7A.

Secondary Membranous Nephropathy

Secondary membranous nephropathy happens due to another condition or exposure. Some common causes include:

Finding the cause of secondary membranous nephropathy is vital. It helps in giving the right treatment and managing the main condition. In some cases, treating the cause can help the nephropathy go into remission and prevent kidney damage.

Pathophysiology of Membranous Nephropathy

Membranous nephropathy is a complex disease. It involves the immune system and the glomerular basement membrane. The disease causes damage and thickening of this membrane, leading to proteinuria and kidney problems.

Immune complexes form in the glomerular basement membrane. These complexes are made of antibodies and antigens. The antigens can be from viruses or bacteria or even from the body itself.

The formation of these complexes starts a chain of events. This includes the activation of the complement system and the recruitment of inflammatory cells. It also leads to the release of cytokines and growth factors.

These factors cause damage and thickening of the glomerular basement membrane. This damage disrupts the glomerular filtration barrier. As a result, proteinuria occurs.

As the disease progresses, more proteins are lost in the urine. This loss can lead to a decrease in blood oncotic pressure. This decrease can cause edema and other symptoms of nephrotic syndrome.

Over time, the inflammation and damage to the glomerular basement membrane can cause scarring. This scarring can lead to a decline in kidney function. Understanding how membranous nephropathy works is key to finding better treatments and improving patient outcomes.

Signs and Symptoms of Membranous Nephropathy

The signs and symptoms of membranous nephropathy vary from person to person. They often include changes in kidney function and fluid balance. A common symptom is proteinuria, which means too much protein in the urine.

Proteinuria and Nephrotic Syndrome

Proteinuria happens when damaged glomeruli let protein leak into the urine. In membranous nephropathy, this can be severe. It’s called nephrotic range when more than 3.5 grams of protein leak daily. When proteinuria is severe, it can lead to low blood protein, high cholesterol, and edema, known as nephrotic syndrome.

Edema and Fluid Retention

Edema, or swelling, is a common symptom. It often shows up in the legs, feet, and ankles. But it can also appear in hands, face, and around the eyes. Edema happens when there’s not enough protein in the blood to keep fluid balanced.

Other Symptoms

People with membranous nephropathy may also have:

• Hypertension (high blood pressure)
• Hyperlipidemia (high blood cholesterol and triglycerides)
• Fatigue and weakness
• Foamy or frothy urine
• Weight gain due to fluid retention

Some people with membranous nephropathy may not notice symptoms early on. It’s key to regularly check kidney function and urinary protein levels. This helps catch the disease early and manage it better.

Diagnosis of Membranous Nephropathy

Diagnosing membranous nephropathy involves several steps. It starts with a clinical evaluation and lab tests. Imaging studies also play a role. The process begins when a patient shows symptoms like proteinuria, edema, or abnormal blood tests.

Urine Tests

Urine tests are key in diagnosing membranous nephropathy. The main sign is significant proteinuria, more than 3.5 grams a day. A 24-hour urine collection or a spot urine test can measure this.

Urinalysis may also show other signs, like microscopic hematuria or lipiduria.

Blood Tests

Blood tests check kidney function and rule out other causes of nephrotic syndrome. They include:

• Serum creatinine and eGFR to check kidney function
• Serum albumin, often low due to protein loss
• Lipid profile, as membranous nephropathy can cause high cholesterol
• Serological tests for secondary causes, like ANA or hepatitis B and C serology

Renal Biopsy

A renal biopsy is the best way to diagnose membranous nephropathy. It involves taking a small kidney tissue sample for microscopic study. The biopsy shows thickened glomerular basement membrane with deposits of immunoglobulins and complement proteins.

Electron microscopy finds subepithelial deposits, a key sign of the disease.

In some cases, more tests are needed. These might include imaging studies or tests for anti-PLA2R antibodies. These are present in many cases of primary membranous nephropathy.

Stages of Membranous Nephropathy

Membranous nephropathy is a major cause of kidney disease in adults. It goes through different stages based on how severe the disease is and how much protein is lost. Knowing these stages helps doctors predict how well a patient will do and what treatment to use.

The stages of membranous nephropathy are typically classified as follows:

In Stage I, patients have less protein loss and normal kidney function. By Stage II, protein loss increases, but kidneys work fine. Stage III shows more protein loss and some kidney damage. Stage IV is the worst, with lots of protein loss and serious kidney damage.

The outlook for membranous nephropathy depends on the stage and how well it responds to treatment. Early stages offer a better chance for recovery and keeping kidneys working. But, advanced stages lead to a higher risk of needing a kidney transplant. Early diagnosis and treatment are key to slowing disease progress and improving life quality.

Treatment Options for Membranous Nephropathy

The treatment for membranous nephropathy varies based on the cause and how severe it is. For idiopathic membranous nephropathy, where no cause is found, the focus is on managing symptoms and slowing the disease. The main treatments are conservative management and immunosuppressive therapy.

Conservative Management

Conservative management aims to control blood pressure, reduce protein loss, and manage swelling. It includes:

• Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to lower blood pressure and protein loss
• Diuretics to manage swelling and fluid buildup
• Statins to control cholesterol and lower heart disease risk
• A low-salt diet and less fluid intake to control swelling

Immunosuppressive Therapy

For severe or worsening idiopathic membranous nephropathy, immunosuppressive therapy is used to control the immune system and reduce inflammation. Common treatments include:

• Corticosteroids (e.g., prednisone)
• Alkylating agents (e.g., cyclophosphamide)
• Calcineurin inhibitors (e.g., cyclosporine, tacrolimus)
• Rituximab, a monoclonal antibody targeting B-cells

The choice of immunosuppressive therapy varies based on the disease’s severity, the patient’s age, and any other health conditions.

Other Treatment Approaches

Other treatments may be used in certain cases:

• Renin-angiotensin system blockade with ACE inhibitors or ARBs to reduce protein loss and slow disease progression
• Anticoagulation therapy in patients at high risk of blood clots
• Vitamin D supplementation to protect bone health in patients with severe protein loss

Regular monitoring and follow-up are key to see how well the treatment is working. Adjustments may be needed. In cases of secondary membranous nephropathy, treating the underlying cause is essential.

Prognosis and Complications of Membranous Nephropathy

The outlook for membranous nephropathy varies. It depends on several things like the cause, how severe nephrotic syndrome is, and how well treatment works. Some people might get better and keep their kidneys working well. But others might see their kidney function get worse over time.

Remission and Relapse

About 30-40% of people with membranous nephropathy get better on their own within 2-3 years. But, up to 30% of those who get better might start to relapse. Those who often relapse or have a lot of protein in their urine are at a higher risk for kidney problems.

Progression to End-Stage Renal Disease

Even with better treatments, many people with membranous nephropathy will end up needing a kidney transplant within 10-15 years. The risk is higher for those with:

• Persistent nephrotic-range proteinuria
• Reduced kidney function at the time of diagnosis
• Older age
• Male gender
• Presence of tubulointerstitial fibrosis on renal biopsy

It’s important to keep a close eye on how well the kidneys are working and how much protein is in the urine. This helps find those at risk early and helps manage their condition better to avoid needing a transplant.

Living with Membranous Nephropathy

Managing membranous nephropathy means making lifestyle and dietary changes. These adjustments help slow kidney disease and reduce complications. They also improve your quality of life.

Dietary Modifications

Diet is key in managing membranous nephropathy. Work with a dietitian to create a meal plan that helps. This plan should lower protein loss and manage other issues.

It’s important to limit sodium to control swelling and blood pressure. Also, eat less protein to ease kidney work. Watch your fluid intake and potassium and phosphorus levels if they’re high.

Lifestyle Changes

Lifestyle changes are also vital. Regular exercise, like walking or swimming, helps keep a healthy weight and blood pressure. But, talk to your doctor before starting any new exercise.

Quitting smoking and drinking less alcohol are also important. They help keep your kidneys healthy and lower complication risks. Stress management, like meditation or yoga, can also help with the emotional side of living with this illness.