What is Minimal Change Disease?
Minimal change disease (MCD), often a cause of a health condition called nephrotic syndrome, occurs commonly in children. This syndrome is a kidney disorder that results in too much protein present in the urine and causes swelling in different parts of the body. Nearly 70-90% of children over the age of one with nephrotic syndrome have MCD, whereas it’s only about 10-15% in adults.
MCD is unique because it causes high levels of protein in the urine, leading to swelling and a decrease of fluid in the blood vessels. However, it typically responds well to steroid treatments. The disease has sometimes been referred to as “minimal change lesion,” “nil disease,” or “lipoid nephrosis”—the latter term refers to the presence of fat droplets in urine as seen under a microscope.
It is noteworthy that children with MCD generally have a very positive outlook for recovery. This means they can expect to get better with appropriate treatment.
What Causes Minimal Change Disease?
Minimal Change Disease usually occurs by itself with no clear cause, a condition we refer to as idiopathic. However, in some rare cases, it may be caused due to exposure to other factors:
* Infections: This could be tuberculosis, syphilis, mycoplasma, ehrlichiosis, or the Hepatitis C virus
* Cancers: Blood-related cancers, including leukemia and types of lymphoma such as Hodgkin and non-Hodgkin
* Allergies: Reactions to bee or jellyfish stings, cat fur, fungi, poison ivy, ragweed pollen, or common house dust
* Medicines: Nonsteroidal anti-inflammatory drugs (NSAIDs), lithium, certain antibiotics like ampicillin or cephalosporins, certain vaccines, and a medication called gamma interferon
* Other kidney diseases: These may include diseases such as IgA nephropathy, SLE (Systemic Lupus Erythematosus – an autoimmune disease), type 1 Diabetes Mellitus, and HIV.
Risk Factors and Frequency for Minimal Change Disease
Minimal change disease is a condition that mainly affects children, with 2 to 7 new cases occurring for every 100,000 children each year. The total number of children with this disease is uncertain, but it’s estimated to be around 10 to 50 cases per 100,000 children. Boys tend to have this disease more often than girls during childhood, but this gender difference disappears as they grow into teenagers. It’s not common for adults to have minimal change disease and we don’t know exactly how many adults get it each year.
- Minimal change disease affects 2 to 7 out of every 100,000 children each year.
- The estimated number of children with the disease is 10 to 50 out of every 100,000.
- Boys are more likely to get this disease than girls during childhood, but this is not the case in the teenage years.
- Adults rarely get minimal change disease.
- The exact number of adults with the disease is unknown.
Signs and Symptoms of Minimal Change Disease
If a person comes to the doctor with swelling (edema) and protein in their urine (proteinuria), the doctor must carefully examine the patient’s medical history and perform a detailed physical exam. This is because proteinuria and edema can be signs of other health issues, like diabetes, side effects from medication, or systemic lupus erythematosus. The patient’s age, family history, and recent illnesses can also provide important clues about what might be causing these symptoms.
Patients with a disease called Minimal Change Disease (MCD) often show up with puffiness around the eyes, swollen genitals, and/or swelling in the lower part of the body. Physical exam can reveal several signs, including widespread body swelling (anasarca), fluid around the heart or lungs (pericardial or pleural effusion), fluid in the abdominal cavity (ascites), and abdominal pain. Individuals with this disease might not have enough fluid in their blood vessels, which can lead to limited urine output (oliguria) and could cause sudden kidney damage. This finding is more common in adults. Kids with MCD often show up with serious infections (like sepsis, pneumonia, and peritonitis), due to a drop in infection-fighting proteins (immunoglobulins).
When adults get Minimal Change Disease, they can present with blood in the urine (hematuria), sudden kidney damage, and high blood pressure.
Testing for Minimal Change Disease
Glomerulonephritis is linked with several different diseases. To find out the cause, doctors must establish whether a patient shows symptoms of nephritic syndrome or nephrotic syndrome. Nephritic syndrome is linked with blood in the urine, protein in the urine, and high blood pressure. Nephrotic syndrome is linked with a high amount of protein in the urine, low levels of the protein albumin in the blood, swelling, high cholesterol, and a higher risk of blood clots.
Patients with nephrotic syndrome may sometimes have low blood volume (referred to as “underfilled”) or high blood volume (referred to as “overfilled”). Low blood volume can happen due to loss of the protein albumin through excess protein in the urine. This leads to a decrease in oncotic pressure—the pressure exerted by proteins in the blood that helps keep fluid in the bloodstream. This causes fluid to move into the areas between cells.
On the other hand, overfilled conditions in nephrotic syndrome are due to problems in the network of tiny blood vessels in the kidneys, which can lead to more sodium and water being retained in the body. Unlike in underfilled patients, in overfilled patients, the excess fluid is not due to low levels of albumin or decreased oncotic pressure. Therefore, it’s important to understand each patient’s fluid volume status before starting treatment to address swelling.
In children, the most common cause of nephrotic syndrome with no known cause is minimal change disease (MCD). In adults, it is the third most common cause, after focal segmental glomerular sclerosis and membranous nephropathy. In adults, a biopsy of the kidney is critical for diagnosing MCD.
For children, MCD is mostly diagnosed based on symptoms, and a biopsy is only needed in the presence of unusual features:
– Symptoms beginning before the age of 1 or after the age of 12
– Noticeable blood in the urine
– Low blood levels of the protein C3
– Very high blood pressure
– High levels of creatinine, a waste product that healthy kidneys remove
– Kidney failure without low blood volume
– History of or positive test results for secondary causes
– Resistance to steroid treatment
Children likely to respond well to steroids usually present with typical symptoms of MCD and are:
– Aged 1-12 years old
– Have normal blood pressure
– Normal kidney function
– Possible microscopic blood in their urine
Basic tests for MCD include checking the urine for protein and microscopic checks for fat bodies and fatty casts—abnormal cells that are indicative of kidney damage. However, a urine dipstick test has limitations; it can’t detail the extent or type of proteinuria as it mainly detects albumin, and it doesn’t pick up other low weight proteins. Also, false positives can occur with the presence of mucus, blood, pus, alkalinity, or concentration. For a more accurate measure, a 24-hour urine collection is necessary.
Also, a spot protein-to-creatinine ratio that is higher than 200 mg/mmol in children and over 300-350 mg/mmol in adults, or protein greater than 3 to 3.5 g/24hours in a 24-hour urine collection in adults indicates nephrotic syndrome. Some of the blood tests that may be conducted include complete metabolic panel, complete blood count, and measurement of total cholesterol and triglyceride levels. Blood tests to rule out secondary causes include tests for antinuclear antibodies, hepatitis B and C, syphilis, HIV, and complement levels.
Treatment Options for Minimal Change Disease
Minimal change disease is a type of kidney disease. The first form of treatment doctors usually try is steroids. Children typically get better within four weeks after starting steroids. On the other hand, adults usually need two months or more to get better. There’s a high chance the disease may return in both children and adults.
For children, the first treatment usually tried is a medication called prednisone. This is taken daily for about 4 to 6 weeks, or every other day for 2 to 5 months. When the dosage is reduced over time, the treatment period typically lasts a minimum of 12 weeks.
For adults, the starting prednisone treatment is similar, but it lasts for about 4 to 16 weeks. After the condition improves, the dose is slowly reduced over 6 months.
For some patients, the disease might persist or return again even after the treatment. This could show as a continued presence of too much protein in urine – a condition called proteinuria. Proteinuria in children which persists after 4 weeks of prednisone treatment, and after 16 weeks for adults, might suggest resistance to steroids. Given the relapses are frequent – two or more relapses in the first six months or four or more relapses within any 12 months. Also, if relapses occur during the reduction phase of steroid treatment or less than two weeks after stopping steroids, it might suggest dependency on steroids. A relapse may also be suspected if there’s too much protein in the urine for three consecutive days.
If a patient’s condition gets worse again, medication, specifically Prednisolone, should be restarted at a certain dose until they are in remission for 3 days. Then, the dose can be reduced over 4 to 8 weeks, a process known as tapering the dose.
For patients who frequently witness disease relapse or who seem dependent on steroids, doctors might consider adding other types of medication that can reduce the need for steroids. These include Cyclophosphamide and Cyclosporine. Cyclophosphamide could have side effects like affecting the reproductive system, hair loss and suppression of bone marrow production. Cyclosporine could potentially cause kidney toxicity, unusual hair growth, high blood pressure and overgrowth of the gums.
However, if the patient cannot tolerate these drugs, alternative medications like Mycophenolate mofetil (MMF) and Rituximab may be considered. MMF is taken twice a day for 1 to 2 years. Rituximab is given once a week for 1 to 4 doses. However, these medications can also have serious side effects that need to be monitored.
What else can Minimal Change Disease be?
When a patient presents with fluid buildup or swelling (known as edema), a doctor will consider several possible causes, which are grouped by the system of the body they affect:
- Heart related: Heart failure
- Liver related: Liver failure or cirrhosis (scarring of the liver)
- Digestive system: Protein-losing enteropathy (a condition where protein is lost from the intestines) or malnutrition
- Kidney related: Acute Glomerulonephritis (a type of kidney inflammation), or kidney failure
- Immune system: Angioedema (swelling beneath the skin), or severe allergic reaction (anaphylaxis)
- Lymphatic system: Primary or secondary lymphedema (lymph fluid buildup), or congenital lymphedema (a condition present from birth)
These conditions all potentially lead to edema as they can lower the pressure inside the blood vessels, causing fluid to leak out into the body’s tissues.
What to expect with Minimal Change Disease
Minimal change disease, a kidney condition, generally has a very positive outlook for patients of all ages, provided that they respond well to treatment with corticosteroids, a type of medication. However, it’s important to note that the main health risks associated with this disease are actually related to the side effects of the medications used in treatment.
Possible Complications When Diagnosed with Minimal Change Disease
People, especially children, with Minimal Change Disease (MCD) often have a heavier than normal amount of protein in their urine. This can cause a variety of complications, including the following:
- Low blood volume, also known as hypovolemia
- Infections like pneumonia, peritonitis, or sepsis. This is because important immune system components are lost through the urine, making it harder to fight off bacteria that cause these infections.
- Venous thromboembolism, a condition where blood clots form in the veins. This is due to a drop in substances that help prevent blood clotting, and an increase in factors that promote it.
- High levels of fat in the blood, known as hyperlipidemia
- Acute kidney injury, which is sudden damage to the kidneys. This usually happens because there isn’t enough fluid in the blood vessels.
Preventing Minimal Change Disease
People experiencing current and severe health issues should eat foods with little to no salt. Alongside this, they should also be mindful of limiting the amount of liquids they consume. This dietary approach is essential for maintaining their health.
