Characteristics of Membranous Nephropathy

Membranous nephropathy is an autoimmune disease in which the body's protective cells attack the renal glomeruli. One-third of the cases remit spontaneously.
Characteristics of Membranous Nephropathy

Last update: 28 July, 2021

Membranous nephropathy, also known as membranous glomerulonephritis is a slowly progressing disease. It occurs when there’s damage in the blood vessels of the kidney (glomeruli) — they thicken as consequence. It’s one of the leading causes of nondiabetic nephrotic syndrome in adults and has an incidence of 8 to 10 cases per million population.

There are two variants of membranous nephropathy (MN):

  • A primary idiopathic one with no apparent cause
  • A secondary one, caused by infections, neoplasms, the consumption of certain drugs, and autoimmune pathologies

Read on to learn more about it.

What’s membranous nephropathy?

MN is one of the most frequent causes of nephrotic syndrome in adults and the elderly, according to the Nefrología al Día journal. Estimates indicate the incidence is of 5-10 cases per million inhabitants per year. Also, up to 85% are of the primary idiopathic type.

The cause of membranous nephropathy is the deposition of antigen-antibody complexes between the glomerular basement membrane (GBM) and podocytes. These latter ones are renal cells attached around the capillaries of the renal corpuscle. Furthermore, the complexes activate the complement system and promote membranous attack.

This attack complex damages the epithelial cells of the glomerulus (a region with tiny tangles of capillaries in the kidney that filter blood and produce urine). Thus, it damages and thickens the renal blood vessels, resulting in organ failure over time.

The attack complex releases proteases, cytokines, and oxidizing substances, which cause injury to the glomerular tissue. As a result, there’s a mismatch in the ionic barriers of the renal structures, and substances that shouldn’t be there, such as proteins, pass into the urine. We know this as proteinuria.

Symptoms associated with membranous nephropathy

According to Orpha.net, the condition usually manifests between the ages of 50 and 60 in the kidneys. Some of the most common clinical signs are:

  • Swelling in legs and ankles. This is due to failures in the renal filtration and leads to fluid accumulation. As a result, edema often appears in the lower extremities of patients.
  • Weight gain. This is due to fluid retention, not an increase in adipose tissue.
  • Foamy urine. This is due to the presence of protein and it’s one of the first signs of nephrotic syndrome.
  • Other nonspecific symptoms such as fatigue and lack of appetite.

Eighty percent of the cases manifest as full nephrotic syndrome. Thus, a person will clearly notice the changes and so detect the disease early. Leg edema is the main reason for consultation.

A doctor looking at a person's legs.
Edema is the accumulation of fluid in the tissues. It’s due to kidney failure and usually affects the legs and face.

Causes of the disease

As we mentioned above, there are two types of nephrotic syndrome, primary and secondary. It’s helpful to know how to differentiate them.

1. Primary membranous nephropathy

According to StatPearls, primary membranous nephropathy corresponds to 75-80% of the total cases. Its cause is idiopathic. However, one of the following antibodies must be present in the affected area in order to detect it. That is, no other possible triggers must be present:

  • 70-80 % of cases are due to antibodies against phospholipase A2 type M receptor autoantigen (PLA2R)
  • 15-20% of cases are due to neural epidermal growth factor (NELL)-like
  • 1-5% of cases are due to antibodies against thrombospondin

In any case, the antibodies adhere to the autoantigens of the organism and promote a targeted attack on the glomerular tissue of the kidneys. Renal function is relatively normal at first but thromboembolic events gradually appear and complicate a person’s well-being.

2. Secondary membranous nephropathy

The remaining 20-25% of cases of nephropathy are the result of underlying conditions such as hepatitis, syphilis, malaria, HIV, or schistosomiasis. It’s also relatively common in cancer patients or in those undergoing certain drug treatments.

Many autoimmune diseases (such as systemic lupus erythematosus) result in MN. This is because a person’s misdirected immune system may wrongly attack the kidneys. There’s an underlying cause of the disease in almost all juvenile patients with membranous nephropathy so it’s secondary.

Possible complications

As per F1000 Research, up to 30% of patients develop end-stage renal disease five to 15 years after the onset of symptoms. However, there are observable spontaneous remissions without any immunosuppressive treatment in 35 to 40% of the cases.

On the contrary, up to 20% of patients have an aggressive condition with marked proteinuria that rapidly progresses to terminal stages. The prognosis is very poor when kidney function declines steadily during the first 12-24 months.

The remaining 40-60% of people with membranous nephropathy progress slowly and steadily. However, the situation is dangerous if there’s no spontaneous remission. A diminished or null renal functionality causes terminal nephrotic syndromes, hypertension, ease of contracting urinary infections, and blood clots.

Diagnosis of membranous nephropathy

The clearest evidence that something’s wrong with the kidneys is the presence of protein in the urine (proteinuria) — as stated by the U.S. National Library of Medicine. Proteins are essential for the body’s homeostasis and energy production and the kidneys’ job is to reabsorb them and keep them from going out along the urine.

There’s a problem when substances the body needs are excreted through urination. A person has proteinuria when the protein content in the urine is equal to, or greater than, 300 milligrams in 24 hours.

Conversely, reduced amounts of protein in the blood also point to this condition. Other chemical tests include blood and urine albumin, urea nitrogen, creatinine, and lipid panel. However, it’s the kidney biopsy that makes the diagnosis certain.

After obtaining a sample of the patient’s renal tissue, diffuse thickening of the capillary and glomerular basement membranes are observable with light microscopy. A physician may also apply histological staining methods to detect antibody activity.

A doctor holding some kidneys.
The kidneys express their malfunction by losing protein with the urine — proteinuria.

Treatment

The goal of the treatment of membranous nephropathy is to reduce symptoms and prevent the progression of the disease as this condition has no cure. However, as we said above, the condition goes away on its own in up to 3 out of 10 patients. Thus, there’s no need for a clinical approach.

Depending on the patient’s degree of proteinuria, one can classify their condition into different categories. In general, some of the drugs prescribed to address membranous nephropathy are:

  • Angiotensin-converting enzyme inhibitors. This is a blood pressure medication that can decrease the amount of protein in the urine. They lower blood pressure so they make it easier for these essential biomolecules to remain in the bloodstream.
  • Diuretics. These drugs lead to the excretion of water and electrolytes through the urine. They don’t cure the disease but can help reduce swelling and edema in the lower extremities.
  • Immunosuppressive medication. As we said above, membranous nephropathy is an autoimmune disease so it may require immunosuppressive therapy to delay damage. Some of the most commonly used drugs are Cytoxan, Rituxan, and prednisone, according to the UNC Kidney Center.

Finally, the most important thing is to treat the underlying cause if the nephropathy is secondary. Thus, it’ll require antibiotics, antiprotozoals, or retroviral if it’s an infection. The removal of the neoplastic mass will be prioritized if it’s due to a tumor.

Patients with membranous nephropathy can’t delay their care

Establishing an absolute prognosis in all cases is difficult for this condition. A third of the patients recover on their own; 10-20% die from rapidly developing complications, and the remaining percentage either stay the same or worsen gradually. In addition, the cause isn’t always clear and sometimes goes away on its own.

However, diuretics, immunosuppressants, and other drugs can considerably extend the patient’s life in cases with a negative prognosis. It depends on the case and on the speed of symptomatic onset.

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