What is minimal change disease

Minimal change disease is a kidney disorder that involves damage to the filtering units of the kidney (glomeruli) that can be seen only with an electron microscope and minimal change disease is the most common cause of idiopathic childhood nephrotic syndrome ¹. Nephrotic syndrome is a group of symptoms that include protein in the urine (proteinuria), low protein levels in the blood, high cholesterol levels, high triglyceride levels, an increased risk for blood clots, and swelling. Other features of this disease include weight gain and a foamy appearance of the urine.

Minimal change disease gets its name because this damage is not visible under a regular microscope. It can only be seen under a very powerful microscope called an electron microscope.

Each kidney is made of more than a million units called nephrons, which filter blood and produce urine.

In minimal change disease, there is damage to the glomeruli. These are the tiny blood vessels inside the nephron where blood is filtered to make urine and waste is removed.

The cause of minimal change disease is unknown, but it may occur following an allergic reaction or infection. Treatment may involve the use of steroids. The fluid retention and high blood pressure that often accompanies minimal change disease may be treated with the use of water pills (diuretics) in combination with a low sodium diet and blood pressure medications (such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin 2 receptor blocker (ARB), calcium channel antagonists).

There is an increased risk for the formation of blood clots (thromboembolic events) and infection in individuals with minimal change disease. It is recommended that individuals with minimal change disease stay active and should a blood clot occur, they may be treated with blood thinners. Infections, such as cellulitis, peritonitis, and pneumonia are common in individuals with minimal change disease and should be treated quickly ².

Will minimal change disease cause kidney failure?

Kidney failure is rare if you have minimal change disease. Almost all children and adults recover from minimal change disease and avoid relapses over the long term. However, some may experience relapses of the protein in the urine, which can often be treated in the same way as the first episode.

Minimal change disease causes

Scientists do not know the exact cause of minimal change disease. In adults, minimal change disease is usually secondary (it is caused by another disease or drug). In children, minimal change disease is usually primary or idiopathic, which means the exact cause is not known.

Minimal change disease is the most common cause of nephrotic syndrome in children. It is also seen in adults with nephrotic syndrome, but is less common.

The cause of minimal change disease is unknown, but if you have secondary causes for minimal change disease, the disease may occur or be related to:

• Allergic reactions
• Use of nonsteroidal anti-inflammatory drugs (NSAIDs)
• Tumors
• Vaccinations (flu and pneumococcal, though rare)
• Viral infections

Minimal change disease symptoms

There may be symptoms of nephrotic syndrome, including:

• Foamy appearance of the urine due to large amounts of protein leaking into your urine, called proteinuria
• Poor appetite
• Swelling called edema (especially around the eyes, feet, and ankles, and in the abdomen), due to fluid building up in your body
• Weight gain (from fluid retention), due to the fluid your body is not able to get rid of

Minimal change disease does not reduce the amount of urine produced. It rarely progresses to kidney failure.

Minimal change disease diagnosis

Your health care provider may not be able to see any signs of minimal change disease, other than swelling. Blood and urine tests reveal signs of nephrotic syndrome, including:

• High cholesterol
• High levels of protein in the urine (proteinuria)
• Low levels of albumin in the blood (hypoalbuminemia)

Tests and procedures used to diagnose nephrotic syndrome include:

• Urine tests. A urinalysis can reveal abnormalities in your urine, such as large amounts of protein, if you have nephrotic syndrome. You may be asked to collect urine samples over 24 hours for an accurate measure of the protein in your urine.
• Blood tests. If you have nephrotic syndrome, a blood test may show low levels of the protein albumin (hypoalbuminemia) specifically and often decreased levels of blood protein overall. Loss of albumin is often associated with an increase in blood cholesterol and blood triglycerides. Serum creatinine and blood urea also may be measured to assess your overall kidney function.
• A kidney biopsy and examination of the tissue with an electron microscope can show signs of minimal change disease. During a kidney biopsy, a special needle is inserted through your skin and into your kidney.

If a kidney biopsy shows little or no damage under a regular microscope, then a diagnosis of minimal change disease may be made if other symptoms, such as protein in the urine and swelling, are noticed. Because minimal change disease is the most common cause of nephrotic syndrome in children, they first get treated for minimal change disease before getting a kidney biopsy. Most people will have a response in fewer than 8 weeks. If the protein in the urine disappears, the doctors may call the disease steroid-sensitive nephrotic syndrome instead of minimal change disease. If treatment does not improve their symptoms over the course of several months a kidney biopsy is done to see if there is another cause for their symptoms.

Minimal change disease treatment

Medicines called corticosteroids can cure minimal change disease in most children. Some children may need to stay on steroids to keep the disease from returning. It is very important to not stop treatment suddenly. By sticking to the full treatment plan, your child will be less likely to relapse (experience the signs and symptoms again).

In adults, steroids are effective, but less so than in children. Adults may have more frequent relapses and become dependent on steroids.

If steroids are not effective, the provider will likely suggest other medicines. For children who do not respond to traditional treatment they have what is called steroid-resistant nephrotic syndrome. Treatment for steroid-resistant nephrotic syndrome includes other combinations of drugs. It is recommended that children with steroid-resistant nephrotic syndrome take a blood pressure medication (ACE inhibitor or angiotensin 2 receptor blocker [ARB]). These two drugs control high blood pressure and reduce the amount of protein in the urine.

• Cholesterol-reducing medications. Medications called statins can help lower cholesterol levels. However, it’s currently unclear whether or not cholesterol-lowering medications can specifically improve the outcomes of people with nephrotic syndrome, such as avoiding heart attacks or decreasing the risk of early death. Statins include atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Altoprev), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor).
• Blood thinners. Medications called anticoagulants help decrease your blood’s ability to clot and may be prescribed if you’ve had a blood clot to reduce your risk of future blood clots. Anticoagulants include heparin, warfarin (Coumadin, Jantoven), dabigatran (Pradaxa), apixaban (Eliquis) and rivaroxaban (Xarelto).

Swelling may be treated with:

• Angiotensin-converting-enzyme inhibitor (ACE inhibitor) medicines. Medications in this category include benazepril (Lotensin), captopril and enalapril (Vasotec). Another group of drugs that works in a similar way is called angiotensin 2 receptor blockers (ARBs) and includes losartan (Cozaar) and valsartan (Diovan). Other medications, such as renin inhibitors, also may be used, though ACE inhibitors and angiotensin 2 receptor blockers are generally used first.
• Blood pressure control
• Diuretics (water pills). Water pills (diuretics) help control swelling by increasing your kidneys’ fluid output. Diuretic medications typically include furosemide (Lasix). Others may include spironolactone (Aldactone) and thiazides, such as hydrochlorothiazide.

How is minimal change disease treated in adults?

The treatment for nephrotic syndrome in adults with minimal change disease is usually with a type of drug called a corticosteroid, often called steroids. You may notice that you start getting better within weeks, or less, although it may take an adult longer to respond than a child. It is important to stick with your treatment plan until all medications are finished; even if your symptoms go away sooner

If you are a woman and want to have children, you should speak with your healthcare provider to see how the medicines you are given affect this process.

For symptoms of swelling (edema), your healthcare provider may give you:

• ACE inhibitor or angiotensin 2 receptor blocker (ARB) medicines
• Diuretics (water pills)
• Limit sodium (salt) in your diet

Minimal change disease diet

Changes to your diet may help you cope with nephrotic syndrome. Your doctor may refer you to a dietitian to discuss how what you eat can help you cope with the complications of nephrotic syndrome. A dietitian may recommend that you:

• Choose lean sources of protein
• Reduce the amount of fat and cholesterol in your diet to help control your blood cholesterol levels
• Eat a low-salt diet to help control the swelling (edema) you experience
• Limit foods that increase blood sugar levels when taking medications that can lead to weight gain, such as steroids

Some people with nephrotic syndrome may also be deficient in the mineral zinc. A recent study showed treatment with zinc supplements in children under 18 improved nephrotic syndrome. But always check with your doctor before giving your child a supplement or taking one yourself to avoid any potential adverse interactions.

Minimal change disease relapse

Other medications that may be used in instances of minimal change disease recurrence include those that are used to treat certain types of cancer (cyclophosphamide, chlorambucil, rituximab) and those that suppress the immune system (cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil) ².

Minimal change disease prognosis

Children usually respond better to corticosteroids than adults. Children often respond within the first month.

A relapse can occur. The condition may improve after long-term treatment with corticosteroids and medicines that suppress the immune system (immunosuppressive medicines).

In individuals who are not treated, there is an increased risk for infection and blood clotting events. About 5-10% of untreated adults may have spontaneous remission (resolution) of disease within a few months.

One major indication of the long-term outcome of minimal change disease is the initial response to corticosteroid treatment. About 80-95% of adults with minimal change disease who receive treatment via corticosteroids experience complete remission of symptoms. About half of all adults treated for minimal change disease have remission within four weeks, while 10-25% require longer treatment. minimal change disease may recur or relapse in about half of all adults. This usually occurs within one year of treatment ³.

Despite the potential for the disease to recur, the occurrence of kidney failure and end stage renal disease is rare ².

References

1. Nephrotic Syndrome. https://www.merckmanuals.com/home/kidney-and-urinary-tract-disorders/kidney-filtering-disorders/nephrotic-syndrome
2. Minimal-Change Disease. https://emedicine.medscape.com/article/243348-overview
3. Treatment of minimal change disease in adults. https://www.uptodate.com/contents/treatment-of-minimal-change-disease-in-adults