Membranous Nephropathy (MN) Samples

Bay Biosciences provides high-quality biopsy tissue samples, formalin fixed paraffin embedded (FFPE) tissue blocks, with matched fresh frozen sera (serum), plasma, and peripheral blood mononuclear cells (PBMC) bio-fluids, from patients diagnosed with membranous nephropathy (MN).

The sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid specimens are processed from patients peripheral whole-blood using customized collection and processing protocols from membranous nephropathy (MN).

Fresh frozen tissue and matched biofluid samples were, collected from unique patients diagnosed with membranous nephropathy (MN).

Bio-samples are provided to a valued pharmaceutical customer for research, diagnostics, discovery, and drug development.

Membranous Nephropathy (MN) Overview

Membranous nephropathy (MN), also called membranous glomerulonephritis, is a rare kidney disease that affects the filters, or glomeruli, of the kidneys. These filters usually help remove waste and fluids.

But when the glomeruli become Inflamed, the kidneys may swell and stop working properly. The filters can fail to keep protein out of the urine, which can lead to problems in other body functions. The symptoms of his condition is known as nephrotic syndrome.

Membranous nephropathy (MN) is an autoimmune disease, and it is chronic. But it is also rare: about 8 to 10 cases per million patients get this disease. MN is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults over 40 years of age.

Anyone can get membranous nephropathy, but it’s more common in older Caucasian men. Children rarely get this kidney condition, and it’s less common in women.

Fifty per cent of patients diagnosed with primary MN continue to have nephrotic syndrome and 30% of patients may progress to end-stage renal disease over 10 years.

Disease onset is typically between 50-60 years of age, presenting with either nephrotic syndrome (edema with confirmed proteinuria, hypoalbuminemia and hyperlipidemia), or nephrotic-range or sub-nephrotic proteinuria.

Renal function is typically normal at presentation. Disease progression is gradual, and occasionally complicated by thrombo-embolic events. Hematuria, hypertension, and reduced glomerular filtration rate can present initially or develop during the disease course.

End stage renal disease (ESRD) develops in up to a third of patients 10 years after disease onset.

MN is an autoimmune disease limited to the kidney. Antibodies to the podocyte antigen m-type phospholipase receptor (PLA2R) are detectable in approximately 70% of patients, and antibodies against thrombospondin type-1 domain-containing 7A (THSD7A) in approximately 3% of patients.

The pathophysiology of antibody formation is unclear. A genetic predisposition and associations with HLA genes and with polymorphisms in the PLA2R gene have been found.

Types of Membranous Nephropathy (MN)

There are two types of membranous nephropathy (MN):

• Primary Membranous Nephropathy: This type happens by itself and directly involves the kidneys. You may hear this type referred to as idiopathic.

 

• Secondary Membranous Nephropathy: This type happens when you have some other bodily problem that has affected your kidneys.

 

Causes of Membranous Nephropathy (MN)

The glomeruli have a layer of tissue, or membrane, that helps filter waste and fluid from the blood. Membranous nephropathy is caused by a thickening of this membrane.‌

Exact causes of why this thickening happens is not clear, but it is caused by immune cells. In primary membranous nephropathy, the body makes antibodies, or protective proteins, that target proteins for the kidneys. This leads to a deposit of immune cells in the kidney filters that cause inflammation and thickening. The thickening stops your kidneys from working, which causes you to lose a lot of protein through the urine. 

Secondary membranous nephropathy is caused by other health problems or treatments that affect the kidneys. These can include the following:

• Diabetes
• Rheumatoid arthritis
• Lupus
• Sjögren’s syndrome
• Heavy metal poisoning
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Probenecid
• Penicillamine
• Hepatitis B
• Hepatitis C
• Syphilis
• HIV
• Malaria 
• Cancer, especially lung cancer and colon cancers

Signs and Symptoms of Membranous Nephropathy (MN)

Symptoms of membranous nephropathy can be different for everyone. Following are some are the common symptoms of MN:

• Swelling 
• Fatigue
• Frequent urination
• Foamy or frothy urine
• Weight gain
• Loss of appetite
• Blood pressure (hypertension) problems
• Peeing less
• Shortness of breath
• Trouble breathing
• Weakness

Swelling is often the first thing MN patients notice. It usually starts in the feet, ankles, and legs and then moves to the rest of the body. ‌The loss of protein causes swelling. As you lose protein, fluid leaks out of the blood vessels into the tissues, which causes fluid buildup. Sometimes fluid can gather in the lungs, which might make it hard for the patient to breathe.

• Blood Tests: Blood tests are used to look for antibodies and other conditions. Doctors might order a patients blood test to check for infections and for levels of: 
  • Blood protein
  • Lipids
  • Blood albumin 
  • Cryoglobulin
  • Blood urea nitrogen
  • Creatinine levels
  • Other markers

 

• Imaging Tests: The doctor might do a CT (computed tomography) scan, or an ultrasound, or MRI (magnetic resonance imaging) to look at the patients kidneys. This will help find any damage and rule out other possibilities.

 

• Kidney Biopsy: A doctor will perform a biopsy procedure to take a small piece of your kidney tissue. They will examine the cells and confirm the diagnosis.

Diagnostic Methods

Typically, the final diagnosis of membranous nephropathy (MN) is made on kidney biopsy. Diagnostic features include capillary wall thickening, normal cellularity, IgG and C3 along capillary walls on immunofluorescence, and sub-epithelial deposits on electron microscopy. However, a diagnosis of MN is strongly suspected on detection of circulating anti-phospholipase A2 receptor (Anti-PLA2R) antibodies.

Treatment of Membranous Nephropathy (MN)

There is no cure for membranous nephropathy. The doctors will focus on treating and managing the symptoms and making the patients immune system stronger. Treatment for MN also depends on the type and cause of the disease.

Doctors may prescribe the following medications for the treatment of membranous nephropathy:

• ACE (angiotensin-converting enzyme) inhibitors:  Drugs that manage high blood pressure, lower urine protein levels and help reduce inflammation in the kidneys.
• ARBs (angiotensin receptor blockers):  ARBs are also known as angiotensin II receptor antagonists, these are used to treat high blood pressure and heart failure and chronic kidney disease.
• Blood Thinners: These are used in patients who have high risk of blood clots.
• Diuretics: These are medicines that remove excess fluids from the body and help lower the blood pressure.
• Low-Salt Diet: Your doctor will recommend reducing salt intake to reduce edema.
• Statins (cholesterol-lowering medications): These drugs help MN patients reduce the elevated cholesterol levels. 

 If any of the previously mentioned factors are present or the proteinuria does not decline during the observation period, your nephrologist will likely use immunosuppressive therapy.

• Immunosuppressive therapy: Drugs to stop the immune system from producing the antibody that attacks the kidneys, including:
  • Corticosteroids
  • Rituximab
  • Cyclosporine 
  • Cyclophosphamide

In some patients with secondary MN, treating the underlying condition may stop kidney damage from further progressing.

Prevention of Membranous Nephropathy (MN)

For most cases of membranous nephropathy, there is not anything that can be done to prevent it since it is an autoimmune process. For those cases caused by other disease, treating and controlling those diseases may help reduce complications from them, such as MN.

Outlook of Membranous Nephropathy (MN)

The prognosis for membranous nephropathy (MN) varies depending on the patient. In some cases, the disease goes away on its own without treatment. For others the disorder can continue for many years without getting worse.

Some patients with membranous nephropathy (MN) end up with kidney failure. These type of patients may need a kidney transplant or dialysis, which is a long-term treatment where a machine filters the blood for the kidneys.

Membranous nephropathy (MN) can come back after treatment. Nephrologist’s usually monitor the kidney function regularly to look for signs if the disease has returned or not. This monitoring will allow the doctor to treat the patient  as soon as possible if MN recurs.

A nephrologist may also keep the patient on medication to suppress the immune system for longer periods of time to reduce the chances of a flare-up occurring.

 

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