Minimal Change Disease (Glomerulonephritis Minimal Lesion)

Minimal change disease, Lipoid nephrosis, Nil disease, Minimal change lesion, Minimal change nephrotic syndrome

Minimal change disease is a kidney disorder that causes the tiny filters in your kidneys to leak protein into your urine, leading to swelling throughout the body. It is the most common cause of kidney problems in children, though adults can also develop this condition.

Table of contents

• What Is Minimal Change Disease?
• Causes and Risk Factors
• Signs and Symptoms
• How Is It Diagnosed?
• Treatment Options
• Outlook and Prognosis

What Is Minimal Change Disease?

Minimal change disease is a disorder that damages the glomeruli, which are clusters of tiny blood vessels in your kidneys that filter waste products from your blood^[1]. The disease gets its unusual name because the damage cannot be seen under a regular light microscope. It can only be detected using a very powerful electron microscope^[2].

The kidneys contain more than one million filtering units called nephrons. Each nephron includes a glomerulus surrounded by a capsule, which acts as a collecting space^[3]. When minimal change disease damages these structures, protein that should remain in your blood leaks into your urine instead. This protein loss leads to several problems throughout the body.

Minimal change disease accounts for 70% to 90% of cases of nephrotic syndrome in children older than one year. However, it is much less common in adults, representing only 10-15% of adult nephrotic syndrome cases^[2].

Causes and Risk Factors

In most cases, especially in children, the exact cause of minimal change disease is unknown. Doctors call this idiopathic or primary minimal change disease^[4]. The disease is thought to involve a disorder of T cells, which are immune system cells. These T cells may release substances called cytokines that injure the tiny foot-like structures on the glomerular cells, leading to protein leakage^[7].

In adults, minimal change disease is more often secondary, meaning it develops as a result of another disease or exposure. Secondary causes can include^[2]:

• Infections such as tuberculosis, syphilis, mycoplasma, ehrlichiosis, hepatitis C virus, and HIV
• Blood cancers including leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma
• Allergic reactions to bee or jellyfish stings, cat fur, fungi, poison ivy, ragweed pollen, or house dust
• Medications including NSAIDs (pain relievers like ibuprofen), lithium, and certain antibiotics such as ampicillin and cephalosporins
• Other immune conditions like IgA nephropathy, lupus, or type 1 diabetes

During childhood, boys develop minimal change disease about twice as often as girls. However, this gender difference disappears during the teenage years^[2]. The incidence is estimated at 2 to 7 new cases per 100,000 children each year.

Signs and Symptoms

Many people with minimal change disease may not notice symptoms initially. However, the most common signs are related to nephrotic syndrome, a group of symptoms that occur together when the kidneys are damaged^[4].

The main symptom is proteinuria, which means high levels of protein in the urine. This can make your urine appear foamy or bubbly^[4]. When the body loses protein through the urine, it causes edema, or swelling, as fluid builds up in body tissues. This swelling is often most noticeable around the eyes, ankles, and feet.

Other symptoms may include^[2]:

• Weight gain due to fluid buildup in the body
• Poor appetite
• Abdominal pain
• Nausea

People with minimal change disease typically have normal blood pressure and normal kidney function, which helps distinguish it from other kidney diseases^[7]. The condition rarely reduces the amount of urine produced and does not commonly progress to kidney failure.

In addition to proteinuria and edema, nephrotic syndrome includes low levels of protein in the blood (called hypoalbuminemia), high cholesterol levels (hyperlipidemia), and an increased tendency to form blood clots (hypercoagulability)^[4].

How Is It Diagnosed?

Diagnosis begins with a medical history and physical examination. Your healthcare provider will ask about your symptoms and check for swelling in your body^[4].

Several tests are used to evaluate kidney function and diagnose minimal change disease:

Urine tests can detect protein and blood in the urine. In children, the critical level for diagnosis is proteinuria of more than 40 mg per hour per square meter of body surface area. In adults, the threshold is more than 3.5 grams per day^[7].

Blood tests measure protein levels, cholesterol, and waste products in the blood. They can also check how well your kidneys are filtering waste, which is called the glomerular filtration rate or GFR^[4].

Kidney biopsy is a procedure where a small sample of kidney tissue is removed using a special needle and examined under a microscope. Under a regular light microscope, the glomeruli appear normal. However, an electron microscope shows swelling and changes in the foot processes of podocytes, which are specialized cells in the glomeruli^[2].

In children with typical symptoms of nephrotic syndrome, doctors often start treatment without performing a kidney biopsy, because minimal change disease is so common in this age group. In adults, a kidney biopsy is usually needed to confirm the diagnosis and rule out other conditions like focal segmental glomerulosclerosis^[2].

Treatment Options

The main treatment for minimal change disease is corticosteroids, often simply called steroids. These medications reduce swelling and suppress the immune system. The most commonly used steroid is prednisone^[4].

Approximately 80% to 90% of patients respond to steroid treatment. Children typically respond faster than adults, often within 2 weeks of starting treatment. Adults may take up to 16 weeks to respond^[10]. After the protein in the urine disappears, treatment continues for several more weeks at lower doses to prevent the disease from returning.

If the disease does not respond to steroids or keeps coming back, your doctor may recommend other medications such as^[10]:

• Cyclophosphamide or chlorambucil (medications that suppress the immune system)
• Calcineurin inhibitors like cyclosporine or tacrolimus
• Mycophenolate mofetil
• Rituximab

In addition to medications that treat the underlying disease, supportive treatments help manage symptoms:

Diuretics (water pills) like furosemide help reduce swelling by helping the body eliminate excess fluid. However, these should be used carefully, as people with minimal change disease may already have low blood volume despite appearing swollen^[10].

Blood pressure medications, particularly ACE inhibitors and ARBs, can help reduce the amount of protein leaking into the urine. Blood pressure and kidney function should be monitored closely when using these medications^[10].

Dietary changes are also important. You may be advised to reduce the amount of salt in your diet to help control swelling. Your healthcare provider or dietitian can provide specific guidance based on your individual needs^[4].

Because steroid treatment and the disease itself can increase your risk of infections, your doctor may recommend vaccines for pneumonia and seasonal flu. Established infections must be treated aggressively^[10].

Outlook and Prognosis

The outlook for minimal change disease is generally very good, especially in children. Most patients achieve complete remission, meaning the disease goes away^[2]. Children tend to have a particularly excellent prognosis.

However, the disease can relapse, meaning it comes back after treatment. The majority of patients who initially respond to steroids will experience at least one relapse. Some people develop frequent relapses and may need long-term treatment with lower doses of medication^[12].

Adults generally have a slower response to treatment than children, but up to 80-90% still achieve remission. Adults may experience relapses more frequently than children and may become dependent on steroids to keep the disease under control^[12].

Unlike some other kidney diseases, minimal change disease rarely progresses to chronic kidney disease or kidney failure. With proper treatment, kidney function typically remains normal^[14]. Spontaneous remissions, where the disease goes away on its own without treatment, can occur in about one-third or more of cases^[12].