What is Nephrotic Syndrome?

Nephrotic Syndrome (NS) is a medical condition characterized by high levels of protein in the urine, which can lead to reduced protein in the blood, increased fat in the blood, swelling, and several complications. It happens when the filtering units of the kidneys, called the glomeruli, are damaged, allowing too much protein to escape from the blood into the urine. This can result from kidney diseases or from other conditions like certain infections, diabetes, lupus, cancer, or even certain drug usage.

The condition is defined by something called ‘nephrotic-range proteinuria’, which simply means that the loss of protein in the urine is significant – three grams or more in a 24-hour urine sample, or two grams in a single sample in relation to another substance called creatinine. Interestingly, it can also happen due to other systemic diseases, like a condition called amyloidosis that leads to the deposit of abnormal proteins in organs.

Nephrotic syndrome can affect both children and adults, regardless of their gender or race. In children, facial swelling is often the first noticeable symptom. In adults, the condition often shows up as dependent edema – swelling in lower parts of the body due to fluid accumulation. Another form of this condition called nephritic syndrome, is associated with inflammation in the glomeruli, which causes blood in the urine and affects kidney function.

Other common symptoms include feeling tired and losing appetite. Correctly identifying these signs is key to managing the condition in a timely manner to prevent serious health complications.

What Causes Nephrotic Syndrome?

Nephrotic syndrome happens when your kidneys don’t work as intended, which can be due to different conditions specific to the kidneys themselves, like membranous nephropathy, minimal-change nephropathy and focal glomerulosclerosis. Sometimes, other issues in the body (systemic diseases) might be behind it, such as lupus, diabetes, and a condition called amyloidosis.

Nephrotic syndrome can also be passed down in the family due to gene changes in specific proteins found in the kidneys, such as podocin, nephrin, or the cation channel 6 protein.

It’s also worth noting that infections, especially upper respiratory tract infections can trigger nephrotic syndrome in almost half of cases, while an allergic reaction could be the cause for a third of cases. Less commonly, an insect bite or even a vaccination could trigger it. Even illicit substances like heroin are known to cause nephrotic syndrome.

Some specific secondary causes of nephrotic syndrome include the following:

– Diabetes
– Autoimmune diseases like lupus
– Several infections like HIV, hepatitis B or C, cytomegalovirus and others.
– A reaction after using some over-the-counter painkillers or gold salts
– The presence of certain blood proteins due to underlying conditions like amyloidosis and paraproteinemias.

In children, the most common cause is a kidney condition called minimal change glomerulonephritis. In white adults, it’s usually membranous nephropathy, while for those of African descent, focal segmental glomerulosclerosis is often the cause.

Also, women in their third trimester of pregnancy could experience high levels of protein in their urine (proteinuria), which is a sign of nephrotic syndrome. This increase in protein might be something new or could be due to pre-existing kidney disease that has worsened over the course of the pregnancy.

Even certain medications might cause nephrotic syndrome. These include some over-the-counter painkillers and drugs like gold, bucillamine, and penicillamine, used for conditions like arthritis. Other medications that can cause it include bisphosphonates, which are used to strengthen bones, as well as lithium and interferon therapy.

Risk Factors and Frequency for Nephrotic Syndrome

Nephrotic syndrome is a serious long-term disease that typically affects children. It’s estimated that there are between two and seven new cases every year for every 100,000 children under 18. While it is seen more often in young boys than girls, the difference disappears when children reach their teenage years. Unfortunately, nephrotic syndrome tends to occur more frequently and severely in children of African American and Hispanic backgrounds.

Let’s look at some statistics from different parts of the world:

United States: Nephrotic syndrome associated with diabetes is seen the most, with about 50 cases for every million people overall and 20 cases out of every million children in particular.
International: In India and Turkey, children’s kidney biopsies were similar to those seen in the West. The same was true for adults in Pakistan. However, while parasitic diseases like malaria and schistosomiasis are linked to nephrotic syndrome in parts of the Middle East and Africa, this connection is not yet well established.
Africa: Research into African children’s causes of nephrotic syndrome found that standard kidney conditions such as minimal change disease and focal and segmental glomerulosclerosis are often found.

In terms of ethnicity, gender, and age:

American Indians, African Americans, and Hispanics see a higher rate of nephrotic syndrome, possibly due to the higher prevalence of diabetes within these communities.
HIV-associated kidney problems, often seen in African Americans, can also turn into nephrotic syndrome.
Focal glomerulosclerosis, another cause of nephrotic syndrome, is seen more often in African American children as compared to white children.
Nephrotic syndrome is more prevalent in males, as is the case with chronic kidney disease in general. However, lupus nephritis, a form of nephrotic syndrome, is predominantly seen in women.

Signs and Symptoms of Nephrotic Syndrome

Nephrotic syndrome is a condition often seen in children that starts with facial swelling. This condition then escalates to swelling of the entire body. Adults with this condition may have swelling in the lower part of their body. It’s also common to have bubbles in the urine, feel tired, and have a loss appetite. Sometimes, the first sign could be a blood clot in the leg veins or lungs. Other symptoms could also point to what’s causing the nephrotic syndrome, such as recent use of non-steroidal anti-inflammatory drugs (NSAIDs) or having diabetes for over 10 years with nerve symptoms.

The most noticeable physical mark of nephrotic syndrome is the swelling, especially around the eyes and legs. With time, the swelling spreads throughout the body, causes weight gain, and might lead to fluid build-up in the abdomen or chest cavity. Blood in the urine and high blood pressure might be present but happen more often in nephritic syndrome. The exact symptoms can depend on the cause of the nephrotic syndrome and whether the kidneys are working normally. For example, someone with a long history of diabetes might have related eye issues. If kidney function is not normal, the person may have a low red blood cell count, high blood pressure, or both.

Facial swelling
Body swelling
Bubbly urine
Tiredness
Loss of appetite
Blood clots in leg veins or lungs (might be the first sign)
Swelling around the eyes and legs
Generalized body swelling leading to weight gain
Possible fluid build-up in the abdomen or chest
Possible blood in the urine
Possibly high blood pressure

Testing for Nephrotic Syndrome

If your doctor suspects you have nephrotic syndrome, a condition that damages the blood-filtering units of your kidneys, they will carry out various tests.

The first test is typically a urine test. High levels of protein in your urine, a condition known as proteinuria, can indicate kidney damage. Your doctor will be looking for readings of 3+ or 4+ on the dipstick test or other similar tests. A 3+ reading usually means you have a protein concentration of 300 mg/dL or more in your urine, which suggests a daily loss of 3 grams or more, and hence falls into the nephrotic range. Doctors also collect urine samples over 24 hours for a more accurate measurement of proteinuria.

A urinalysis can show the presence of different types of “casts,” which are tube-shaped proteins that can mean damage to your kidneys. Also, finding lipids (or fats) in your urine, a condition called lipiduria, suggests a problem with the filtering units of your kidneys.

Blood tests commonly show low levels of a protein called albumin in nephrotic syndrome. Albumin levels are often below the normal range of 3.5 to 4.5 g/dL. Also, the levels of creatinine, a waste product that your kidneys should eliminate, might vary depending on how severe the kidney damage is. Another thing doctors keep an eye on is cholesterol and triglyceride levels, which are often high in nephrotic syndrome.

Some other tests might be carried out depending on your symptoms. These might include tests for conditions like diabetes, autoimmune diseases, Hepatitis B and C, syphilis, and HIV amongst other tests. These test results can sometimes influence your treatment plan and help your doctor decide if a kidney biopsy is needed or not.

Ultrasonography (an ultrasound scan) is another common method to check for kidney problems. This test is especially important for people with only one kidney, as they’re more prone to a condition called focal glomerulosclerosis. Ultrasonography can also help measure the level of fibrosis or scarring in the kidneys.

A renal biopsy, in which a small sample of kidney tissue is removed and examined under a microscope, can also be done. This is usually recommended in cases like congenital nephrotic syndrome, steroid resistance, frequent relapses or steroid dependency, and significant other kidney problem signs. Kidney biopsies usually show that disorders of the blood-filtering units of the kidneys cause the high protein levels in the urine, not damage to the tubules (long tube-like structures) of the kidneys.

A type of protein called “phospholipase A Receptor (PLA R)” is often found on the surface of podocytes, the cells that help filter your blood in your kidneys. In about 70% of people with a type of nephrotic syndrome called “idiopathic membranous nephropathy,” their immune system produces antibodies against PLA R. The level of these antibodies in your blood can help monitor the activity of the disease and the effectiveness of treatment. If these antibodies are absent, it may indicate a type of nephrotic syndrome associated with cancers.

Treatment Options for Nephrotic Syndrome

Before starting a medication called corticosteroids for a condition called nephrotic syndrome, doctors conduct a detailed assessment where they monitor the patient’s height, weight, and blood pressure. They also check for infections and other conditions that might be affecting the body overall.

The treatment for nephrotic syndrome varies depending on the cause and the patient’s age group. For example, the treatment differs between adults and children. There are also guidelines designed by a group known as Kidney Disease Improving Global Outcomes (KDIGO) that doctors follow to treat the syndrome.

In children, the main treatment usually involves using corticosteroids. But for kids who often relapse or depend on steroids, other medications like cyclophosphamide, MMF, inhibitory drugs, and levamisole may be used. If all of these fail, there are stronger drugs such as MMF or high dose steroids that can be attempted. Another medication called rituximab, which targets and deletes certain immune cells known as B cells, can be an effective alternative. However, in children who depend on both inhibitory drugs and steroids, rituximab may sometimes fail.

In adults, the treatment differs based on the specific cause of nephrotic syndrome. For example, prednisone is often effective in cases caused by minimal changes in the kidney. In cases related to a form of lupus called lupus nephritis, prednisone, combined with cyclophosphamide or MMF, is typically used. For nephrotic syndrome resulting from secondary amyloidosis, management of the primary disease can help to improve the condition.

In children, acute nephrotic syndrome, which comes on suddenly, can often be managed without hospitalizing the patient, with close outpatient follow-up care and proper education for the parents and patient. However, hospitalization might become necessary in severe cases, such as intense swelling, complications like bacterial peritonitis, pneumonia, sepsis or clot-related complications, or if the patient is not improving.

Diuretics, or water tablets, can be helpful to deal with fluid buildup, and antibiotics like penicillin may be used to prevent infections. In case of possible or confirmed bacterial infections, treatments should be started on a priority basis. Non-immune patients should also consider taking preventative treatment when exposed to chickenpox.

In adults, the principles of treatment for acute nephrotic syndrome remain the same. They might need diuretics, and in some cases, blood-thinning medication to prevent complications related to blood clots. In diseases causing nephrotic syndrome, such as diabetes, drugs are used to reduce protein leakage from the kidneys and indirectly cause blood pressure to drop.

Besides medication, diet and activity adjustments play a crucial role in managing nephrotic syndrome. A balanced diet with enough calories and protein can help maintain good health. A low-salt diet can also help reduce fluid retention and swelling. Regular immunizations are important unless the patient is experiencing flare-ups or is taking immunity-damping medications.

When a doctor suspects that a patient has nephrotic syndrome, they need to consider several other possible underlying conditions that may be causing the patient’s symptoms. These conditions can be grouped based on the body system primarily affected, including:

Hepatic (liver-related): Such as liver failure, cirrhosis, and Budd-Chiari syndrome
Digestive: Problems like fluid leakage from the intestines (exudative enteropathy), blockage of lymph vessels in the intestines (lymphangiectasia), and poor nutrition
Cardiac: Conditions like hereditary angioneurotic edema (a genetic disorder causing swelling)
Immune: Conditions like serious allergic reactions (anaphylaxis)
Renal (kidney-related): Conditions such as chronic glomerulonephritis (inflammation of the kidneys), diabetic nephropathy (kidney damage due to diabetes), focal segmental glomerulosclerosis (scarring of the kidneys), HIV-associated nephropathy, IgA nephropathy (kidney inflammation due to immune system activity), membranous glomerulonephritis (inflammation and thickening of the kidneys), and minimal change disease

What to expect with Nephrotic Syndrome

People showing minimal change disease have an excellent chance of recovery, with most people going into remission or their condition improving after treatment with steroids. However, 85 to 90% of these patients respond to steroids and may experience a return of their symptoms, putting them at risk for damage from long-term use of these drugs, getting systemic infections, and other complications.

For patients with a disease called focal-segmental glomerulosclerosis (FSGS), which affects the kidneys, the outlook is less positive. Most patients with FSGS eventually will need dialysis and a kidney transplant. Only about 20% of patients with this condition experience a reduction of protein in their urine; another 10% get better, but continue to have protein in their urine. Between 25 and 30% of patients with FSGS will develop a disease called end-stage renal disease (ESRD), where the kidneys stop working within five years. It’s interesting to note that some studies suggest adults in China with primary FSGS may fare better over a 5-year period compared to those in the west.

For patients suffering from another type of kidney disease called membranous nephropathy, around 30% recover naturally. However, for patients with persistent nephrotic syndrome, a condition that causes too much protein to be excreted in the urine, 40% to 50% will develop ESRD over a period of ten years.

Possible Complications When Diagnosed with Nephrotic Syndrome

Nephrotic syndrome, or kidney disorders that cause a patient to excrete too much protein in their urine, can lead to a number of metabolic issues such as:

Infections
Low calcium levels and bone abnormalities
High levels of fat in the blood and increased chance of artery disease
An increased tendency for the blood to clot
Low blood volume

One serious complication that can arise from this is Acute Kidney Injury, which is typically caused by low blood volume or systemic infection. Moreover, it is also suggested that kidney swelling could lead to a decrease in the rate at which the kidneys filter blood. Additional issues that may stem from this include:

High blood pressure due to decreased kidney capacity and fluid retention
Malnutrition due to the gut being swollen and not absorbing nutrients properly
Collection of fluid in the abdomen and around the lungs
General body swelling
Difficulties in breathing
Systemic infection
Inflammation of the thin tissue that lines the inside of your abdomen
Blood clots
Failure to grow or develop at a normal rate

Preventing Nephrotic Syndrome

It is advisable for patients to follow a diet low in salt, as this can assist in controlling their symptoms. For those with nephrotic syndrome – a kidney disorder that causes the body to excrete too much protein in urine – there is no need to limit physical activity. Staying active is actually better than bed rest, as it helps lower the chances of developing blood clots.

Steroids are sometimes used for treatment but may have side-effects like stunting growth. To ensure patients are not adversely affected, they should have regular check-ups every three months at a clinic. It’s also important to note that steroid use can affect bone health. To counteract this, patients might need to take extra calcium and vitamin D.

Additionally, having an annual eye examination is necessary to detect potential issues like cataracts. Within the community, keeping up to date with vaccinations is very important for those with nephrotic syndrome. This ensures that patients have the best chance of avoiding other illnesses that could make their condition worse.

Frequently asked questions

The prognosis for Nephrotic Syndrome varies depending on the specific condition and individual factors. Here are some key points about the prognosis: - People with minimal change disease, a common cause of Nephrotic Syndrome, have an excellent chance of recovery, with most going into remission or experiencing improvement after treatment with steroids. - For patients with focal-segmental glomerulosclerosis (FSGS), the outlook is less positive. Most patients with FSGS will eventually need dialysis and a kidney transplant, and a significant percentage will develop end-stage renal disease (ESRD) within five years. - For patients with membranous nephropathy, around 30% recover naturally, but for those with persistent nephrotic syndrome, 40% to 50% will develop ESRD over a period of ten years.

Nephrotic syndrome can be caused by various conditions specific to the kidneys, systemic diseases in the body, gene changes in specific proteins found in the kidneys, infections, allergic reactions, insect bites, vaccinations, illicit substances, certain medications, and pregnancy.

Signs and symptoms of Nephrotic Syndrome include: - Facial swelling - Body swelling - Bubbly urine - Tiredness - Loss of appetite - Blood clots in leg veins or lungs (might be the first sign) - Swelling around the eyes and legs - Generalized body swelling leading to weight gain - Possible fluid build-up in the abdomen or chest - Possible blood in the urine - Possibly high blood pressure It's important to note that the exact symptoms can vary depending on the cause of the nephrotic syndrome and the overall kidney function. For example, individuals with a long history of diabetes might experience related eye issues. Additionally, if kidney function is not normal, there may be a low red blood cell count, high blood pressure, or both.

The types of tests that are needed for Nephrotic Syndrome include: - Urine test to check for proteinuria and measure protein concentration in the urine - Urinalysis to look for the presence of casts and lipids in the urine - Blood tests to check for low levels of albumin, variations in creatinine levels, and high cholesterol and triglyceride levels - Additional tests depending on symptoms, such as tests for diabetes, autoimmune diseases, Hepatitis B and C, syphilis, and HIV - Ultrasonography to check for kidney problems and measure fibrosis or scarring - Renal biopsy to examine kidney tissue under a microscope - Blood test to check for the presence of antibodies against phospholipase A Receptor (PLA R) in idiopathic membranous nephropathy - Detailed assessment of height, weight, blood pressure, and overall health before starting medication - Other tests as needed to determine the cause and appropriate treatment for Nephrotic Syndrome.

The doctor needs to rule out the following conditions when diagnosing Nephrotic Syndrome: 1. Hepatic (liver-related) conditions such as liver failure, cirrhosis, and Budd-Chiari syndrome. 2. Digestive problems like fluid leakage from the intestines (exudative enteropathy), blockage of lymph vessels in the intestines (lymphangiectasia), and poor nutrition. 3. Cardiac conditions like hereditary angioneurotic edema (a genetic disorder causing swelling). 4. Immune conditions like serious allergic reactions (anaphylaxis). 5. Renal (kidney-related) conditions such as chronic glomerulonephritis (inflammation of the kidneys), diabetic nephropathy (kidney damage due to diabetes), focal segmental glomerulosclerosis (scarring of the kidneys), HIV-associated nephropathy, IgA nephropathy (kidney inflammation due to immune system activity), membranous glomerulonephritis (inflammation and thickening of the kidneys), and minimal change disease.

When treating Nephrotic Syndrome, there can be several side effects, including: - Infections - Low calcium levels and bone abnormalities - High levels of fat in the blood and increased chance of artery disease - Increased tendency for blood clotting - Low blood volume - Acute Kidney Injury - High blood pressure - Malnutrition - Collection of fluid in the abdomen and around the lungs - General body swelling - Difficulties in breathing - Systemic infection - Inflammation of the thin tissue that lines the inside of the abdomen - Blood clots - Failure to grow or develop at a normal rate

You should see a nephrologist for Nephrotic Syndrome.

Nephrotic syndrome is estimated to affect between two and seven new cases every year for every 100,000 children under 18.

The treatment for Nephrotic Syndrome varies depending on the cause and the age group of the patient. In children, the main treatment usually involves using corticosteroids. However, if children often relapse or depend on steroids, other medications like cyclophosphamide, MMF, inhibitory drugs, and levamisole may be used. In severe cases, stronger drugs such as MMF or high dose steroids can be attempted. Rituximab, which targets and deletes certain immune cells, can be an effective alternative. In adults, the treatment differs based on the specific cause of Nephrotic Syndrome. Prednisone is often effective in cases caused by minimal changes in the kidney. For cases related to lupus nephritis, prednisone combined with cyclophosphamide or MMF is typically used. Management of the primary disease can help improve the condition in cases of Nephrotic Syndrome resulting from secondary amyloidosis. In both children and adults, diuretics, antibiotics, and lifestyle adjustments such as diet and activity modifications are important components of treatment.

Nephrotic Syndrome is a medical condition characterized by high levels of protein in the urine, which can lead to reduced protein in the blood, increased fat in the blood, swelling, and several complications. It occurs when the filtering units of the kidneys, called the glomeruli, are damaged, allowing too much protein to escape from the blood into the urine.