Membranous Nephropathy - Causes, Symptoms, Diagnosis, and Treatment

What Is Membranous Nephropathy?

Membranous nephropathy is a type of glomerular disease which is characterized by damage and thinning of the blood vessels of the glomerulus. The glomerulus is a part of the nephron which filters the waste from the blood. Membranous nephropathy is also called membranous glomerulopathy or membranous glomerulonephritis. It is an autoimmune disease that leads to inflammation of the kidney structures and impairs the normal functioning of the kidney.

An autoimmune disease is a condition that occurs when the body's immune system attacks the healthy tissues, cells, and organs of the body. Membranous nephropathy involves proteinuria; the greater the protein urea, the long-term the risk for renal failure occurs. Primary membranous nephropathy is an autoimmune disease. It is generally seen in older adults with circulating anti-PLA2R antibodies that are predominantly. Nephrotic syndrome is most commonly caused by membranous nephropathy. The changes in the glomerulus affected by the disease lead to leakage of large amounts of protein into the urine called proteinuria.

What Causes Membranous Nephropathy?

There are two types of membranous nephropathy -

1. Idiopathic or Primary Membranous Nephropathy: It is the most common type of membranous nephropathy. It is caused by an autoimmune response of the immune system. It is caused when an antibody attacks a protein on the podocytes called phospholipase A2 receptor PLA2R. Instead of targeting a foreign body, these antibodies attack podocytes. Podocytes are the cells of the glomerulus.

2. Secondary Membranous Nephropathy: Secondary membranous nephropathy can be caused by certain conditions such as hepatitis B viral infection, administration of non-steroidal anti-inflammatory drugs, systemic lupus erythematosus, cancer, and other diseases and infections.

What Are the Symptoms of Membranous Nephropathy?

• Proteinuria - The presence of protein in the urine is proteinuria.

• Hypoalbuminemia - Damage to the cells of the glomerulus leads to leakage of protein, especially albumin.

• Dyslipidemia - Imbalance in the lipid mechanism leading to high cholesterol levels.

• Acute Kidney Injury - Kidney injury can occur due to the thinning of the basement membrane of the glomerulus.

• Peripheral Edema - Swelling in the legs and feet can be seen due to fluid retention in the body.

• Frothy Urine - Foamy appearing urine can be seen due to the presence of protein in the urine.

• Hypertension - A rise in blood pressure occurs when the kidneys start to fail.

• Weight Gain - Fluid retention causes an increase in body weight.

How Is Membranous Nephropathy Diagnosed?

1. Blood Test - Blood samples can be taken to measure the level of fat and protein in the blood. It is also needed to calculate the glomerular filtration rate (GFR). Serum metabolic panel to detect blood urea nitrogen, creatinine, electrolytes, vitamin D levels, uric acid, and estimated glomerular filtration rate. Lipid profile to assess for dyslipidemia.

2. Urine Test - Urine samples can be taken to detect the presence of protein, creatinine levels, and microscopy for cellular casts, fat oval bodies, and fatty casts. Urine protein or urine albumin to creatinine levels, and microscopy for cellular casts, fat oval bodies, and fatty casts.

3. Kidney Biopsy - A kidney biopsy is considered to be the most reliable test to confirm the diagnosis of membranous nephropathy. The procedure involves taking a sample of kidney tissue with a needle and examining it under an electron microscope. It helps in detecting the membranous changes in the kidney.

4. Antibody Levels - A blood sample is taken to measure the level of antibodies against the phospholipase A2 receptor.

5. Radiological Investigations -

• Ultrasonography - Kidney ultrasound is used to study the kidneys for radiological kidney disease, the presence of obstruction, and renal vein thromboembolism.

• Renal Vein Doppler and Computer Tomography or Magnetic Resonance Angiography - These are used to screen renal vein thrombosis.

• Computed Tomography Angiogram of the Chest - CT scan is used to detect the presence of pulmonary embolism.

• Lower Extremity Doppler - This technique is used for detecting deep vein thrombosis.

What Are the Complications Associated With Membranous Nephropathy?

Complications from membranous nephropathy can include health issues such as high cholesterol, severe swelling, and kidney failure. Other complications that can happen due to membranous nephropathy include -

• Renal vein thrombosis is a blood clot in the renal vein, and it can be a life-threatening complication that can require emergency medical treatment.

• Deep vein thrombosisis a blood clot in the legs.

• Pulmonary embolism is a blood clot in the lungs.

• It can also lead to hyperlipidemia, chronic kidney disease, hypertension, and compromised cardiovascular health.

• Side effects of immunotherapy such as the increased risk of infections and malignancies.

• Risk of development of renal tubular acidosis and stones from chemotherapy.

• Infertility risk associated with Cyclophosphamide.

• Reactivation of infections like hepatitis B and tuberculosis with Rituximab.

• Calcineurin inhibitors can cause nephrotoxicity, neurotoxicity, renal parenchyma fibrosis, hair loss, and pancreatic toxicity.

• Steroids increase the risk of infections, metabolic syndrome, hypertension from salt and fluid retention, psychosis, and gastrointestinal irritation.

• The end-stage renal disease requires renal replacement therapy and concomitant complications related to the procedure.

• Risk of catheter-associated bacterial infections, hypotension, accelerated cardiovascular morbidity and mortality, and neurological side-effects.

How Is Membranous Nephropathy Treated?

Management of membranous nephropathy depends upon the type and cause. In case of primary membranous nephropathy with a moderate level of proteinuria and stable kidney function without complications such as a blood clot, the treatment can include-

• Angiotensin-Converting Enzyme Inhibitors - These medications are used to control high blood pressure, reduce inflammation in the kidneys, and lower urine protein levels.

• Cholesterol-Lowering Drugs - Statins can help reduce elevated cholesterol levels.

• Diuretics - Diuretics are the drugs that remove excess fluid from the body and lower blood pressure.

• Low-Salt Diet - Reduction in the intake of salt helps to reduce edema.

• Immunosuppressive Therapy - Drugs that suppress the immune system in order to prevent the antibodies from attacking the kidney include corticosteroids, Cyclophosphamide, and Cyclosporin.

Conclusion :

Membranous nephropathy can certainly progress into kidney failure. Treatment can help in slowing down the process of kidney disease but cannot completely eradicate the disease. In such cases, kidney failure can be treated by a kidney transplant or dialysis. The disease progression can be slowed down by treating the symptoms to reduce the severity. People with membranous nephropathy need to be monitored for any signs and symptoms or changes in the kidney structure. It is very important to know the side effects of the medications that have been prescribed.